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Sample records for simplex virus-mediated human

  1. Human Herpes Simplex Virus Type 1 in Confiscated Gorilla

    PubMed Central

    Oxford, Kristie L.; Gardner-Roberts, David; Kinani, Jean-Felix; Spelman, Lucy; Barry, Peter A.; Cranfield, Michael R.; Lowenstine, Linda J.

    2014-01-01

    In 2007, we detected human herpes simplex virus type 1, which caused stomatitis, in a juvenile confiscated eastern lowland gorilla (Gorilla beringei graueri) that had a high degree of direct contact with human caretakers. Our findings confirm that pathogens can transfer between nonhuman primate hosts and humans. PMID:25341185

  2. Human herpes simplex virus type 1 in confiscated gorilla.

    PubMed

    Gilardi, Kirsten V K; Oxford, Kristie L; Gardner-Roberts, David; Kinani, Jean-Felix; Spelman, Lucy; Barry, Peter A; Cranfield, Michael R; Lowenstine, Linda J

    2014-11-01

    In 2007, we detected human herpes simplex virus type 1, which caused stomatitis, in a juvenile confiscated eastern lowland gorilla (Gorilla beringei graueri) that had a high degree of direct contact with human caretakers. Our findings confirm that pathogens can transfer between nonhuman primate hosts and humans.

  3. Evolutionary origins of human herpes simplex viruses 1 and 2.

    PubMed

    Wertheim, Joel O; Smith, Martin D; Smith, Davey M; Scheffler, Konrad; Kosakovsky Pond, Sergei L

    2014-09-01

    Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. The primate simplex viruses exemplify this pattern of virus-host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only primate species known to be infected with two distinct herpes simplex viruses: HSV-1 and HSV-2. Human herpes simplex viruses are ubiquitous, with over two-thirds of the human population infected by at least one virus. Here, we investigated whether the additional human simplex virus is the result of ancient viral lineage duplication or cross-species transmission. We found that standard phylogenetic models of nucleotide substitution are inadequate for distinguishing among these competing hypotheses; the extent of synonymous substitutions causes a substantial underestimation of the lengths of some of the branches in the phylogeny, consistent with observations in other viruses (e.g., avian influenza, Ebola, and coronaviruses). To more accurately estimate ancient viral divergence times, we applied a branch-site random effects likelihood model of molecular evolution that allows the strength of natural selection to vary across both the viral phylogeny and the gene alignment. This selection-informed model favored a scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose from a cross-species transmission event from the ancestor of modern chimpanzees to an extinct Homo precursor of modern humans, around 1.6 Ma. These results provide a new framework for understanding human herpes simplex virus evolution and demonstrate the importance of using selection-informed models of sequence evolution when investigating viral origin hypotheses.

  4. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

    SciTech Connect

    Vafai, A.; Wellish, M.; Devlin, M.; Gilden, D.H. ); Murray, R.S. Veterans Administration Medical Center, Denver, CO )

    1988-04-01

    Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia.

  5. Human herpes simplex virus: life cycle and development of inhibitors.

    PubMed

    Kukhanova, M K; Korovina, A N; Kochetkov, S N

    2014-12-01

    WHO reports that 90% of human population is infected by different types of herpesviruses, which develop latency or cause oral and genital herpes, conjunctivitis, eczema herpeticum, and other diseases. Herpesvirus almost always accompanies HIV-infection and complicates AIDS treatment. Herpes simplex virus type 1 is one of the most wide spread viruses from the Herpesviridae family. HSV virion, genome structure, replication mechanisms, antiherpes drug development strategies, including design of prodrugs, and mutations causing ACV-resistance in clinical HSV isolates are discussed in this review. PMID:25749169

  6. Human cytomegalovirus function inhibits replication of herpes simplex virus

    SciTech Connect

    Cockley, K.D.; Shiraki, K.; Rapp, F.

    1988-01-01

    Human embryonic lung (HEL) cells infected with human cytomegalovirus (HCMV) restricted the replication of herpes simplex virus type 1 (HSV-1). A delay in HSV replication of 15 h as well as a consistent, almost 3 log inhibition of HSV replication in HCMV-infected cell cultures harvested 24 to 72 h after superinfection were observed compared with controls infected with HSV alone. Treatment of HCMV-infected HEL cells with cycloheximide (100 ..mu..g/ml) for 3 or 24 h was demonstrated effective in blocking HCMV protein synthesis, as shown by immunoprecipitation with HCMV antibody-positive polyvalent serum. Cycloheximide treatment of HCMV-infected HEL cells and removal of the cycloheximide block before superinfection inhibited HSV-1 replication more efficiently than non-drug-treated superinfected controls. HCMV DNA-negative temperature-sensitive mutants restricted HSV as efficiently as wild-type HCMV suggesting that immediate-early and/or early events which occur before viral DNA synthesis are sufficient for inhibition of HSV. Inhibition of HSV-1 in HCMV-infected HEL cells was unaffected by elevated temperature (40.5/sup 0/C). However, prior UV irradiation of HCMV removed the block to HSV replication, demonstrating the requirement for an active HCMV genome. HSV-2 replication was similarly inhibited in HCMV-infected HEL cells. Superinfection of HCMV-infected HEL cells with HSV-1 labeled with (/sup 3/H)thymidine provided evidence that the labeled virus could penetrate to the nucleus of cells after superinfection. Evidence for penetration of superinfecting HSV into HCMV-infected cells was also provided by blot hybridization of HSV DNA synthesized in cells infected with HSV alone versus superinfected cell cultures at 0 and 48 h after superinfection.

  7. Replication of type 2 herpes simplex virus in human endocervical tissue in organ culture.

    PubMed Central

    Birch, J.; Fink, C. G.; Skinner, G. R.; Thomas, G. H.; Jordan, J. A.

    1976-01-01

    The replication of type 2 herpes simplex virus in human endocervical tissue in organ culture was investigated. The temporal profile of virus replication was related to the initial virus inoculum; high input inocula induced a rapid increase in virus titre while lower multiplicities induced a more slow-rising increase in virus titre. Our evidence suggested that explants were capable of initiating and supporting virus replication for at least 2 weeks following establishment of the culture. Virus yields were optimal when explants were cultured at 37 degrees and in serum-supplemented medium. Explants also supported the replication of type 1 herpes simplex virus and a "non-human" herpes simplex virus (pseudo-rabies virus). The optimal conditions for replication of type 2 herpes simplex virus in human endocervical explants have been established and will provide a model permitting precise investigation of lytic or other virus-cervical cell interactions and their possible relationship to herpes virus-induced pre-invasive carcinoma of this organ. Images Fig. 1 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:183806

  8. Herpes simplex virus 2 modulates apoptosis and stimulates NF-{kappa}B nuclear translocation during infection in human epithelial HEp-2 cells

    SciTech Connect

    Yedowitz, Jamie C.; Blaho, John A. . E-mail: john.blaho@mssm.edu

    2005-11-25

    Virus-mediated apoptosis is well documented in various systems, including herpes simplex virus 1 (HSV-1). HSV-2 is closely related to HSV-1 but its apoptotic potential during infection has not been extensively scrutinized. We report that (i) HEp-2 cells infected with HSV-2(G) triggered apoptosis, assessed by apoptotic cellular morphologies, oligosomal DNA laddering, chromatin condensation, and death factor processing when a translational inhibitor (CHX) was added at 3 hpi. Thus, HSV-2 induced apoptosis but was unable to prevent the process from killing cells. (ii) Results from a time course of CHX addition experiment indicated that infected cell protein produced between 3 and 5 hpi, termed the apoptosis prevention window, are required for blocking virus-induced apoptosis. This corresponds to the same prevention time frame as reported for HSV-1. (iii) Importantly, CHX addition prior to 3 hpi led to less apoptosis than that at 3 hpi. This suggests that proteins produced immediately upon infection are needed for efficient apoptosis induction by HSV-2. This finding is different from that observed previously with HSV-1. (iv) Infected cell factors produced during the HSV-2(G) prevention window inhibited apoptosis induced by external TNF{alpha} plus cycloheximide treatment. (v) NF-{kappa}B translocated to nuclei and its presence in nuclei correlated with apoptosis prevention during HSV-2(G) infection. (vi) Finally, clinical HSV-2 isolates induced and prevented apoptosis in HEp-2 cells in a manner similar to that of laboratory strains. Thus, while laboratory and clinical HSV-2 strains are capable of modulating apoptosis in human HEp-2 cells, the mechanism of HSV-2 induction of apoptosis differs from that of HSV-1.

  9. Latent Herpes Simplex Virus 1 Infection Does Not Induce Apoptosis in Human Trigeminal Ganglia

    PubMed Central

    Lindemann, Anja; Sinicina, Inga; Strupp, Michael; Brandt, Thomas; Hüfner, Katharina

    2015-01-01

    Herpes simplex virus 1 (HSV-1) can establish lifelong latency in human trigeminal ganglia. Latently infected ganglia contain CD8+ T cells, which secrete granzyme B and are thus capable of inducing neuronal apoptosis. Using immunohistochemistry and single-cell reverse transcription-quantitative PCR (RT-qPCR), higher frequency and transcript levels of caspase-3 were found in HSV-1-negative compared to HSV-1-positive ganglia and neurons, respectively. No terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-positive neurons were detected. The infiltrating T cells do not induce apoptosis in latently infected neurons. PMID:25762734

  10. High Efficiency Latency and Activation of Herpes Simplex Virus in Human Cells

    NASA Astrophysics Data System (ADS)

    Wigdahl, Brian L.; Scheck, Adrienne C.; de Clercq, Erik; Rapp, Fred

    1982-09-01

    Herpes simplex virus (HSV) exists in humans in a latent form that can be activated. To characterize the molecular basis of the cell-virus interactions and to analyze the state of the latent HSV genome, an in vitro model system was established. In this system a large fraction of the latently infected cells contain an HSV genome that can be activated. Cell survival was reduced minimally after repression of high multiplicity HSV type 1 (HSV-1) infection of human fibroblast cells with (E)-5-(2-bromovinyl)-2'-deoxyuridine in combination with human leukocyte interferon (IFN-α ). A minimum of 1 to 3 percent of the surviving cells contained an HSV genome that could be activated either by human cytomegalovirus superinfection or reduction in incubation temperature.

  11. [Use of the nested polymerase chain reaction in the differential diagnosis of human herpes simplex virus].

    PubMed

    Glukhov, A I; Gordeev, S A; Al'tshuler, M L; Severin, S E

    2003-02-01

    Herpes is one of the most widespread human viral pathologies. The article depicts a special modification of polymerized chain reaction--(PCR)--(referred to as "nested"), which has a higher sensitivity, specificity and reliability as compared to the ordinary PCR, and which is designed to detect the herpes viruses. The method was initially tested at purified preparation of viral DNA, and later--at clinical materials obtained from patients and healthy donors. Secretions from the urogenital tract (smears), scrapes from the urogenital tracts and urinal cellular samples were examined in patients. Herpes simplex was detected in all cases. As for the healthy people, the identical examinations produced in them mainly the negative findings. Therefore, the nested PCR is a simple, sensitive and effective instrument in the diagnostics and prevention of herpes; it can be recommended for a comprehensive usage in medical practice.

  12. Antiviral activity of mycosynthesized silver nanoparticles against herpes simplex virus and human parainfluenza virus type 3

    PubMed Central

    Gaikwad, Swapnil; Ingle, Avinash; Gade, Aniket; Rai, Mahendra; Falanga, Annarita; Incoronato, Novella; Russo, Luigi; Galdiero, Stefania; Galdiero, Massimilano

    2013-01-01

    The interaction between silver nanoparticles and viruses is attracting great interest due to the potential antiviral activity of these particles, and is the subject of much research effort in the treatment of infectious diseases. In this work, we demonstrate that silver nanoparticles undergo a size-dependent interaction with herpes simplex virus types 1 and 2 and with human parainfluenza virus type 3. We show that production of silver nanoparticles from different fungi is feasible, and their antiviral activity is dependent on the production system used. Silver nanoparticles are capable of reducing viral infectivity, probably by blocking interaction of the virus with the cell, which might depend on the size and zeta potential of the silver nanoparticles. Smaller-sized nanoparticles were able to inhibit the infectivity of the viruses analyzed. PMID:24235828

  13. Directed Selection of Recombinant Human Monoclonal Antibodies to Herpes Simplex Virus Glycoproteins from Phage Display Libraries

    NASA Astrophysics Data System (ADS)

    Sanna, Pietro Paolo; Williamson, R. Anthony; de Logu, Alessandro; Bloom, Floyd E.; Burton, Dennis R.

    1995-07-01

    Human monoclonal antibodies have considerable potential in the prophylaxis and treatment of viral disease. However, only a few such antibodies suitable for clinical use have been produced to date. We have previously shown that large panels of human recombinant monoclonal antibodies against a plethora of infectious agents, including herpes simplex virus types 1 and 2, can be established from phage display libraries. Here we demonstrate that facile cloning of recombinant Fab fragments against specific viral proteins in their native conformation can be accomplished by panning phage display libraries against viral glycoproteins "captured" from infected cell extracts by specific monoclonal antibodies immobilized on ELISA plates. We have tested this strategy by isolating six neutralizing recombinant antibodies specific for herpes simplex glycoprotein gD or gB, some of which are against conformationally sensitive epitopes. By using defined monoclonal antibodies for the antigen-capture step, this method can be used for the isolation of antibodies to specific regions and epitopes within the target viral protein. For instance, monoclonal antibodies to a nonneutralizing epitope can be used in the capture step to clone antibodies to neutralizing epitopes, or antibodies to a neutralizing epitope can be used to clone antibodies to a different neutralizing epitope. Furthermore, by using capturing antibodies to more immunodominant epitopes, one can direct the cloning to less immunogenic ones. This method should be of value in generating antibodies to be used both in the prophylaxis and treatment of viral infections and in the characterization of the mechanisms of antibody protective actions at the molecular level.

  14. Recombinant adeno-associated virus mediates a high level of gene transfer but less efficient integration in the K562 human hematopoietic cell line.

    PubMed Central

    Malik, P; McQuiston, S A; Yu, X J; Pepper, K A; Krall, W J; Podsakoff, G M; Kurtzman, G J; Kohn, D B

    1997-01-01

    We tested the ability of a recombinant adeno-associated virus (rAAV) vector to express and integrate exogenous DNA into human hematopoietic cells in the absence of selection. We developed an rAAV vector, AAV-tNGFR, carrying a truncated rat nerve growth factor receptor (tNGFR) cDNA as a cell surface reporter under the control of the Moloney murine leukemia virus (MoMuLV) long terminal repeat. An analogous MoMuLV-based retroviral vector (L-tNGFR) was used in parallel, and gene transfer and expression in human hematopoietic cells were assessed by flow cytometry and DNA analyses. Following gene transfer into K562 cells with AAV-tNGFR at a multiplicity of infection (MOI) of 13 infectious units (IU), 26 to 38% of cells expressed tNGFR on the surface early after transduction, but the proportion of tNGFR expressing cells steadily declined to 3.0 to 3.5% over 1 month of culture. At an MOI of 130 IU, nearly all cells expressed tNGFR immediately posttransduction, but the proportion of cells expressing tNGFR declined to 62% over 2 months of culture. The decline in the proportion of AAV-tNGFR-expressing cells was associated with ongoing losses of vector genomes. In contrast, K562 cells transduced with the retroviral vector L-tNGFR expressed tNGFR in a constant fraction. Integration analyses on clones showed that integration occurred at different sites. Integration frequencies were estimated at about 49% at an MOI of 130 and 2% at an MOI of 1.3. Transduction of primary human CD34+ progenitor cells by AAV-tNGFR was less efficient than with K562 cells and showed a declining percentage of cells expressing tNGFR over 2 weeks of culture. Thus, purified rAAV caused very high gene transfer and expression in human hematopoietic cells early after transduction, which steadily declined during cell passage in the absence of selection. Although the efficiency of integration was low, overall integration was markedly improved at a high MOI. While prolonged episomal persistence may be adequate

  15. Human cytomegalovirus renders cells non-permissive for replication of herpes simplex viruses

    SciTech Connect

    Cockley, K.D.

    1988-01-01

    The herpes simplex virus (HSV) genome during production infection in vitro may be subject to negative regulation which results in modification of the cascade of expression of herpes virus macromolecular synthesis leading to establishment of HSV latency. In the present study, human embryonic lung (HEL) cells infected with human cytomegalovirus (HCMV) restricted the replication of HSV type-1 (HSV-1). A delay in HSV replication of 15 hr as well as a consistent, almost 1000-fold inhibition of HSV replication in HCMV-infected cell cultures harvested 24 to 72 hr after superinfection were observed compared with controls infected with HSV alone. HSV type-2 (HSV-2) replication was similarly inhibited in HCMV-infected HEL cells. Prior ultraviolet-irradiation (UV) of HCMV removed the block to HSV replication, demonstrating the requirement for an active HCMV genome. HCMV deoxyribonucleic acid (DNA) negative temperature-sensitive (ts) mutants inhibited HSV replications as efficiently as wild-type (wt) HCMV at the non-permissive temperature. Evidence for penetration and replication of superinfecting HSV into HCMV-infected cells was provided by blot hybridization of HSV DNA synthesized in HSV-superinfected cell cultures and by cesium chloride density gradient analysis of ({sup 3}H)-labeled HSV-1-superinfected cells.

  16. Decreased T-cell proliferative response to common environmental antigens could be an indicator of early human immunodeficiency virus-mediated lymphocyte lesions.

    PubMed Central

    Tassinari, P; Deibis, L; Blanca, I; Bianco, N E; Echeverría de Pérez, G

    1995-01-01

    To evaluate CD4+/CD29+ cells and their responses to different antigens in polar stages of human immunodeficiency virus (HIV) infection, we studied 26 HIV-seropositive carriers (SPCs) and 15 patients with AIDS simultaneously with 20 healthy volunteers (HVs) and 10 seronegative homosexual and bisexual men (SNH). CD3, CD4, CD29, and CD45RA phenotypes were analyzed by two-color flow cytometry. Significant depletion of CD4+ T cells and both memory (CD4+/CD29+) and naive (CD4+/CD45RA+) T-cell subsets was found among SPCs and AIDS patients compared with the numbers of such cells in the HV and SNH groups. Responses to optimal doses of Candida albicans, streptokinase, and tetanus toxoid were explored in peripheral blood mononuclear cells and CD4(+)- and CD4+/CD29(+)-enriched cell populations. In SPCs, the response to C. albicans in peripheral blood mononuclear cells showed a statistically significant diminution compared with the response of HVs (15,308 versus 35,951 cpm). In addition, a significantly reduced response to streptokinase was evident only when cell preparations were CD4+/CD29+ enriched (3,048 versus 10,367 cpm). Furthermore, the SPC group comprised seven responders to at least one antigen and seven nonresponders to any of the selected specific antigens. Absence of a response in these latter patients was independent of the absolute counts of memory and naive T-cell populations. The response to tetanus toxoid, although diminished in SPCs, was not significantly different from that in controls. Our results suggest that defective responses to common environmental antigens, unrelated to the absolute number of CD4+/CD29+ cells, is probably an early indicator of an HIV-induced lymphocyte lesion. PMID:7583914

  17. Herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection.

    PubMed

    Skeate, Joseph G; Porras, Tania B; Woodham, Andrew W; Jang, Julie K; Taylor, Julia R; Brand, Heike E; Kelly, Thomas J; Jung, Jae U; Da Silva, Diane M; Yuan, Weiming; Kast, W Martin

    2016-02-01

    Herpes simplex virus (HSV) was originally implicated in the aetiology of cervical cancer, and although high-risk human papillomavirus (HPV) is now the accepted causative agent, the epidemiological link between HSV and HPV-associated cancers persists. The annexin A2 heterotetramer (A2t) has been shown to mediate infectious HPV type 16 (HPV16) uptake by human keratinocytes, and secretory leukocyte protease inhibitor (SLPI), an endogenous A2t ligand, inhibits HPV16 uptake and infection. Interestingly, HSV infection induces a sustained downregulation of SLPI in epithelial cells, which we hypothesized promotes HPV16 infection through A2t. Here, we show that in vitro infection of human keratinocytes with HSV-1 or HSV-2, but not with an HSV-1 ICP4 deletion mutant that does not downregulate SLPI, leads to a >70% reduction of SLPI mRNA and a >60% decrease in secreted SLPI protein. Consequently, we observed a significant increase in the uptake of HPV16 virus-like particles and gene transduction by HPV16 pseudovirions (two- and 2.5-fold, respectively) in HSV-1- and HSV-2-infected human keratinocyte cell cultures compared with uninfected cells, whereas exogenously added SLPI reversed this effect. Using a SiMPull (single-molecule pulldown) assay, we demonstrated that endogenously secreted SLPI interacts with A2t on epithelial cells in an autocrine/paracrine manner. These results suggested that ongoing HSV infection and resultant downregulation of local levels of SLPI may impart a greater susceptibility for keratinocytes to HPV16 infection through the host cell receptor A2t, providing a mechanism that may, in part, provide an explanation for the aetiological link between HSV and HPV-associated cancers.

  18. Enhanced replication of herpes simplex virus type 1 in human cells

    SciTech Connect

    Miller, C.S.; Smith, K.O. )

    1991-02-01

    The effects of DNA-damaging agents on the replication of herpes simplex virus type 1 (HSV-1) were assessed in vitro. Monolayers of human lung fibroblast cell lines were exposed to DNA-damaging agents (methyl methanesulfonate (MMS), methyl methanethiosulfonate (MMTS), ultraviolet light (UV), or gamma radiation (GR)) at specific intervals, before or after inoculation with low levels of HSV-1. The ability of cell monolayers to support HSV-1 replication was measured by direct plaque assay and was compared with that of untreated control samples. In this system, monolayers of different cell lines infected with identical HSV-1 strains demonstrated dissimilar levels of recovery of the infectious virus. Exposure of DNA-repair-competent cell cultures to DNA-damaging agents produced time-dependent enhanced virus replication. Treatment with agent before virus inoculation significantly (p less than 0.025) increased the number of plaques by 10 to 68%, compared with untreated control cultures, while treatment with agent after virus adsorption significantly increased (p less than 0.025) the number of plaques by 7 to 15%. In a parallel series of experiments, cells deficient in DNA repair (xeroderma pigmentosum) failed to support enhanced virus replication. These results suggest that after exposure to DNA-damaging agents, fibroblasts competent in DNA repair amplify the replication of HSV-1, and that DNA-repair mechanisms that act on a variety of chromosomal lesions may be involved in the repair and biological activation of HSV-1 genomes.

  19. Herpes simplex virus type 2 modulates the susceptibility of human bladder cells to uropathogenic bacteria.

    PubMed

    Superti, F; Longhi, C; Di Biase, A M; Tinari, A; Marchetti, M; Pisani, S; Gallinelli, C; Chiarini, F; Seganti, L

    2001-09-01

    The present study analyses the susceptibility of human bladder-derived cells (HT-1376) to the infection by herpes simplex virus type 2 (HSV-2) and Chlamydia trachomatis, as well as to the adhesiveness of uropathogenic bacteria. HT-1376 cells were efficiently infected by HSV-2 strain 333, as demonstrated by immunofluorescence staining of viral antigens, titration of cytopathic effect, and visualisation by transmission electron microscopy. This cell model was also prone to C. trachomatis (serovar E, Bour strain) replication and to the adherence of clinical uropathogenic isolates of Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Enterococcus faecalis. The pre-infection of HT-1376 cells with HSV-2 caused a tenfold increased adherence of an E. coli strain (U1), isolated from a patient affected by severe haemorrhagic cystitis, whereas in HSV-2 pre-infected cells the number of C. trachomatis inclusion bodies was significantly reduced. Our findings indicate that these cells are a suitable in vitro model for studying infection and super-infection of the lower urinary tract by viruses and bacteria.

  20. Vulvar carcinomas: search for sequences homologous to human papillomavirus and herpes simplex virus DNA.

    PubMed

    Pilotti, S; Rotola, A; D'Amato, L; Di Luca, D; Shah, K V; Cassai, E; Rilke, F

    1990-07-01

    Ten cases of intraepithelial carcinoma, five with Bowenoid features and five with early invasion, and ten cases of invasive vulvar carcinoma were examined by in situ hybridization and Southern blot analysis using DNA probes for human papillomavirus (HPV) types 6, 11, 16, 18 and 31. HPV DNA was detected in 90% of the intraepithelial cases and in 10% of the invasive cases. All positive cases showed the presence of DNA of HPV type 16. The cases with intraepithelial lesions revealed a strong correlation between the presence of HPV type 16 DNA, cigarette smoking habit, other potential cofactors such as herpes simplex (HSV) DNA sequences and the use of contraceptive drugs, and clinicopathologic features of Bowen's type in situ squamous cell carcinoma. Similar associations were not observed among the cases with invasive disease. While HPV-16 is associated with differentiated Bowenoid type vulvar intraepithelial neoplasia, which appears to be the most common form of early carcinoma of the vulva, the same association was not seen with respect to advanced vulvar invasive squamous cell carcinoma.

  1. Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, M.; McGrath, M. S.; Hanks, D.; Erickson, S.; Pulliam, L.

    1992-01-01

    We have investigated the direct effect of dimethyl prostaglandin A1 (dmPGA1) on the replication of herpes simplex virus (HSV) and human immunodeficiency virus type 1 (HIV-1). dmPGA1 significantly inhibited viral replication in both HSV and HIV infection systems at concentrations of dmPGA1 that did not adversely alter cellular DNA synthesis. The 50% inhibitory concentration (ID50) for several HSV type 1 (HSV-1) strains ranged from 3.8 to 5.6 micrograms/ml for Vero cells and from 4.6 to 7.3 micrograms/ml for human foreskin fibroblasts. The ID50s for two HSV-2 strains varied from 3.8 to 4.5 micrograms/ml for Vero cells; the ID50 was 5.7 micrograms/ml for human foreskin fibroblasts. We found that closely related prostaglandins did not have the same effect on the replication of HSV; dmPGE2 and dmPGA2 caused up to a 60% increase in HSV replication compared with that in untreated virus-infected cells. HIV-1 replication in acutely infected T cells (VB line) and chronically infected macrophages was assessed by quantitative decreases in p24 concentration. The effective ID50s were 2.5 micrograms/ml for VB cells acutely infected with HIV-1 and 5.2 micrograms/m for chronically infected macrophages. dmPGA1 has an unusual broad-spectrum antiviral activity against both HSV and HIV-1 in vitro and offers a new class of potential therapeutic agents for in vivo use.

  2. Lymphocyte transformation and interferon production in human mononuclear cell microcultures for assay of cellular immunity to herpes simplex virus.

    PubMed Central

    Haahr, S; Rasmussen, L; Merigan, T C

    1976-01-01

    Interferon production and transformation in response to herpes simplex virus antigen were studied in microcultures of human mononuclear cells. Mononuclear cells consisting of monocytes and both T and B lymphocytes were purified by Ficoll-Hypaque gradients. Lymphocytes, predominantly T with 5% B, were obtained by passage of buffy-coat cells through nylon fiber columns. For some experiments, autochthonous macrophages and column-purified lymphocytes were stimulated with herpesvirus antigen. The effect of specific antibody and cell concentration on reactivity is described. Crude and purified antigens were compared as cell culture stimulants. Significant differences in transformation and interferon were observed between donors with a history of herpes labialis and donors with no detectable antibody, both in cultures prepared by Ficoll-Hypaque gradients and by column purification of lymphocytes. Cultures from seronegative donors prepared by Ficoll-Hypaque gradients produced interferon but did not transform when stimulated by herpes simplex antigen. "Immune" interferon production, that is, type II as opposed to type I, occurred only with autochthonous macrophage and column-purified lymphocyte cultures. Interferon produced by Ficoll-Hypaque-purified mononuclear cultures was type I, and its production was unrelated to immune status. Similarly, column-purified lymphocytes responded to herpes simplex virus antigen with type I interferon if obtained from a seropositive donor. PMID:181328

  3. Lentigo Simplex

    MedlinePlus

    ... body, including areas that are not exposed to sunlight. Multiple lentigos are associated with several inherited syndromes, ... as identical to those caused by exposure to sunlight. Who's At Risk Lentigo simplex may occur in ...

  4. Griffithsin and Carrageenan Combination To Target Herpes Simplex Virus 2 and Human Papillomavirus

    PubMed Central

    Levendosky, Keith; Mizenina, Olga; Martinelli, Elena; Jean-Pierre, Ninochka; Kizima, Larisa; Rodriguez, Aixa; Kleinbeck, Kyle; Bonnaire, Thierry; Robbiani, Melissa; Zydowsky, Thomas M.; O'Keefe, Barry R.

    2015-01-01

    Extensive preclinical evaluation of griffithsin (GRFT) has identified this lectin to be a promising broad-spectrum microbicide. We set out to explore the antiviral properties of a GRFT and carrageenan (CG) combination product against herpes simplex virus 2 (HSV-2) and human papillomavirus (HPV) as well as determine the mechanism of action (MOA) of GRFT against both viruses. We performed the experiments in different cell lines, using time-of-addition and temperature dependence experiments to differentiate inhibition of viral attachment from entry and viral receptor internalization. Surface plasmon resonance (SPR) was used to assess GRFT binding to viral glycoproteins, and immunoprecipitation and immunohistochemistry were used to identify the specific glycoprotein involved. We determined the antiviral activity of GRFT against HSV-2 to be a 50% effective concentration (EC50) of 230 nM and provide the first evidence that GRFT has moderate anti-HPV activity (EC50 = 0.429 to 1.39 μM). GRFT blocks the entry of HSV-2 and HPV into target cells but not the adsorption of HSV-2 and HPV onto target cells. The results of the SPR, immunoprecipitation, and immunohistochemistry analyses of HSV-2 combined suggest that GRFT may block viral entry by binding to HSV-2 glycoprotein D. Cell-based assays suggest anti-HPV activity through α6 integrin internalization. The GRFT-CG combination product but not GRFT or CG alone reduced HSV-2 vaginal infection in mice when given an hour before challenge (P = 0.0352). While GRFT significantly protected mice against vaginal HPV infection when dosed during and after HPV16 pseudovirus challenge (P < 0.026), greater CG-mediated protection was afforded by the GRFT-CG combination for up to 8 h (P < 0.0022). These findings support the development of the GRFT-CG combination as a broad-spectrum microbicide. PMID:26369967

  5. Dissection of the Antibody Response against Herpes Simplex Virus Glycoproteins in Naturally Infected Humans

    PubMed Central

    Huang, Zhen-Yu; Whitbeck, J. Charles; Ponce de Leon, Manuel; Lou, Huan; Wald, Anna; Krummenacher, Claude; Eisenberg, Roselyn J.; Cohen, Gary H.

    2014-01-01

    ABSTRACT Relatively little is known about the extent of the polyclonal antibody (PAb) repertoire elicited by herpes simplex virus (HSV) glycoproteins during natural infection and how these antibodies affect virus neutralization. Here, we examined IgGs from 10 HSV-seropositive individuals originally classified as high or low virus shedders. All PAbs neutralized virus to various extents. We determined which HSV entry glycoproteins these PAbs were directed against: glycoproteins gB, gD, and gC were recognized by all sera, but fewer sera reacted against gH/gL. We previously characterized multiple mouse monoclonal antibodies (MAbs) and mapped those with high neutralizing activity to the crystal structures of gD, gB, and gH/gL. We used a biosensor competition assay to determine whether there were corresponding human antibodies to those epitopes. All 10 samples had neutralizing IgGs to gD epitopes, but there were variations in which epitopes were seen in individual samples. Surprisingly, only three samples contained neutralizing IgGs to gB epitopes. To further dissect the nature of these IgGs, we developed a method to select out gD- and gB-specific IgGs from four representative sera via affinity chromatography, allowing us to determine the contribution of antibodies against each glycoprotein to the overall neutralization capacity of the serum. In two cases, gD and gB accounted for all of the neutralizing activity against HSV-2, with a modest amount of HSV-1 neutralization directed against gC. In the other two samples, the dominant response was to gD. IMPORTANCE Antibodies targeting functional epitopes on HSV entry glycoproteins mediate HSV neutralization. Virus-neutralizing epitopes have been defined and characterized using murine monoclonal antibodies. However, it is largely unknown whether these same epitopes are targeted by the humoral response to HSV infection in humans. We have shown that during natural infection, virus-neutralizing antibodies are principally

  6. Morphologic, immunohistochemical, immunologic, ultrastructural, and time-related study of herpes simplex virus type 1-infected cultured human fibroblasts.

    PubMed

    Jensen, Helle L; Norrild, Bodil

    2002-03-01

    Membrane glycoproteins of enveloped animal viruses are synthesized, processed, and transported inside infected cells. Expression of viral glycoproteins on the surface of viral particles and host cells are essential for many biologic functions. In the case of herpes simplex virus, the glycoprotein molecules may act as nucleation points for virus assembly and budding at the nuclear membrane. The temporal distribution of herpes simplex virus type 1 particles and glycoproteins in cultured human fibroblasts was studied by titration plaque assay, immunoblots, immunofluorescence light microscopy, and immunogold cryosection electron microscopy to describe the virus-cell interactions. These concordant analyses revealed significant release of infectious viral particles to the medium at 6 hours postinfection, that the capacity of the host cells to make infectious viral particles was complete at 18 hours postinfection, and that the infection brought time-related modifications of tubulin, cell morphology, and viral glycoproteins. The data presented is in accord with the theory of envelopment at the nuclear membranes containing immature glycoproteins followed by multiple deenvelopments and reenvelopments of the virus particles during the transport and maturation in the endoplasmic reticulum and the Golgi complex.

  7. Exploiting virus stealth technology for xenotransplantation: reduced human T cell responses to porcine cells expressing herpes simplex virus ICP47.

    PubMed

    Crew, Mark D; Phanavanh, Bounleut

    2003-01-01

    Direct recognition of porcine major histocompatibility complex (MHC) proteins by human T cells is well documented. Eliminating donor (porcine) MHC proteins may therefore be beneficial in pig-to-human xenotransplants. To this end, we have attempted to exploit viral stealth mechanisms to eliminate pig MHC class I cell-surface expression. PK(15) (pig kidney) cells stably transfected with the herpes simplex virus (HSV) ICP47 gene [PK(15)-ICP47 cells] exhibited a dramatic reduction of MHC class I cell-surface expression when compared with untransfected PK(15) cells. To test the effect of down-regulation of porcine MHC class I on human cellular immune responses, a human CD8+ enriched T cell line (anti-PK15 T cells) with reactivity towards PK(15) cells was derived by repeated stimulation of human T cells with PK(15) cells stably transfected with the costimulatory molecule B7.1 [PK(15)-B7.1 cells]. Anti-PK15 T cells efficiently lyzed PK(15) cells but not PK(15)-ICP47 (class I negative) cells. Consistent with effector function, anti-PK15 T cells showed a robust proliferative response to PK(15)-B7.1 cells but did not proliferate at all to PK(15)-B7.1 cells which also expressed HSV ICP47. These results suggest that virus stealth technology can be exploited for xenotransplantation.

  8. Construction of a differentiated human hepatocyte cell line expressing the herpes simplex virus-thymidine kinase gene.

    PubMed

    Kobayashi, N; Miyazaki, M; Westerman, K A; Noguchi, H; Sakaguchi, M; Totsugawa, T; Watanabe, T; Matsumura, T; Fujiwara, T; Leboulch, P; Tanaka, N; Namba, M

    2001-01-01

    Transient support using a hybrid artificial liver (HAL) device is a promising treatment for the patients with acute liver failure. Primary human hepatocytes are an ideal source for HAL therapy; however, the number of human livers available for hepatocyte isolation is limited by competition for use in whole organ transplantation. To overcome this problem, we previously established a highly differentiated human fetal hepatocyte cell line OUMS-29. Considering the potential risk when using these genetically engineered cells in humans, additional safeguards should be added to make the cells more clinically useful. In this work, the herpes simplex virus thymidine kinase (HSVtk) gene was retrovirally introduced into OUMS-29 cells. One of the HSVtk-expressed clones, OUMS-29/thymidine kinase (TK), grew in chemically defined serum free medium and expressed the genes of albumin, asialoglycoprotein receptor, glutamine synthetase, glutathione-S-transferase pi, and blood coagulation factor X. In vitro sensitivity of the cells to ganciclovir was evaluated. Intrasplenic transplantation of 50 x 10(6) OUMS-29/TK cells prolonged the survival of 90% hepatectomized rats compared with medium injection alone (control). In the present study, we have established highly differentiated immortalized human hepatocytes with tight regulation. The cells may be clinically useful for HAL treatment. PMID:11575821

  9. Activation of human papillomavirus type 18 gene expression by herpes simplex virus type 1 viral transactivators and a phorbol ester

    SciTech Connect

    Gius, D.; Laimins, L.A.

    1989-02-01

    Several viral trans-activators and a tumor promoter were examined for the ability to activate human papillomavirus type 18 (HPV-18) gene expression. A plasmid containing the HPV-18 noncoding region placed upstream of the chloramphenicol acetyltransferase reporter gene was cotransfected with different herpes simplex virus type 1 (HSV-1) genes into several cell lines. Both HSV-1 TIF and ICPO activated HPV-18 expression; however, activation by TIF was observed only in epithelial cells, while ICPO stimulated expression in a wide variety of cells. The element activated by both TIF and ICOP was mapped to a 229-base-pair fragment which also contains an HPV-18 epithelial cell-preferred enhancer. The inclusion of a papillomavirus E2 trans-activator with TIF and ICOP further increased HPV-18 expression. In contrast, the HSV-1 ICP4 and ICP27 genes, as well as the human T-cell lymphotropic virus type I and human immunodeficiency virus type 1 tat genes, were found to have no effect on HPV-18 expression. In transient assays, the addition of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) also activated HPV-18 expression. The region of HPV-18 activated by TPA was localized to a sequence which is homologous to other TPA-responsive elements.

  10. Herpes Simplex Virus 1 Tropism for Human Sensory Ganglion Neurons in the Severe Combined Immunodeficiency Mouse Model of Neuropathogenesis

    PubMed Central

    Che, Xibing; Reichelt, Mike; Qiao, Yanli; Gu, Haidong; Arvin, Ann

    2013-01-01

    The tropism of herpes simplex virus (HSV-1) for human sensory neurons infected in vivo was examined using dorsal root ganglion (DRG) xenografts maintained in mice with severe combined immunodeficiency (SCID). In contrast to the HSV-1 lytic infectious cycle in vitro, replication of the HSV-1 F strain was restricted in human DRG neurons despite the absence of adaptive immune responses in SCID mice, allowing the establishment of neuronal latency. At 12 days after DRG inoculation, 26.2% of human neurons expressed HSV-1 protein and 13.1% expressed latency-associated transcripts (LAT). Some infected neurons showed cytopathic changes, but HSV-1, unlike varicella-zoster virus (VZV), only rarely infected satellite cells and did not induce fusion of neuronal and satellite cell plasma membranes. Cell-free enveloped HSV-1 virions were observed, indicating productive infection. A recombinant HSV-1-expressing luciferase exhibited less virulence than HSV-1 F in the SCID mouse host, enabling analysis of infection in human DRG xenografts for a 61-day interval. At 12 days after inoculation, 4.2% of neurons expressed HSV-1 proteins; frequencies increased to 32.1% at 33 days but declined to 20.8% by 61 days. Frequencies of LAT-positive neurons were 1.2% at 12 days and increased to 40.2% at 33 days. LAT expression remained at 37% at 61 days, in contrast to the decline in neurons expressing viral proteins. These observations show that the progression of HSV-1 infection is highly restricted in human DRG, and HSV-1 genome silencing occurs in human neurons infected in vivo as a consequence of virus-host cell interactions and does not require adaptive immune control. PMID:23269807

  11. Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus.

    PubMed Central

    Feduchi, E; Alonso, M A; Carrasco, L

    1989-01-01

    The replication of herpes simplex virus type 1 (HSV-1) is not inhibited in either HeLa or HEp-2 cells treated with human alpha interferon (HuIFN-alpha), particularly when high multiplicities of infection are used. However, HuIFN-gamma partially inhibits HSV-1 translation in HEp-2 cells infected at low multiplicities. Under these conditions, the transcription of genes alpha 22, TK, and gamma 0 is greatly diminished. The combined addition of human tumor necrosis factor (TNF) and HuIFN-gamma to HEp-2 cells exerts a synergistic inhibition of HSV-1 translation. Cells treated with both cytokines continue synthesizing cellular proteins, even 20 h after HSV-1 infection. As little as 10 U of IFN-gamma per ml blocked HSV-1 DNA replication, provided that TNF was also present in the medium. Analyses of HSV-1 gene transcription suggest that the action of both TNF and IFN-gamma blocked a step that comes at or prior to early HSV-1 gene expression. This early step in HSV-1 replication inhibited by TNF and IFN-gamma occurs after virus attachment and entry into cells, since the internalization of radioactive HSV-1 virion particles was not blocked by the presence of the two cytokines. Therefore, we conclude that the synergistic action of TNF plus IFN-gamma affects a step in HSV-1 replication that comes after virus entry but before or at the transcription of immediate-early genes. Images PMID:2536838

  12. Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus.

    PubMed

    Feduchi, E; Alonso, M A; Carrasco, L

    1989-03-01

    The replication of herpes simplex virus type 1 (HSV-1) is not inhibited in either HeLa or HEp-2 cells treated with human alpha interferon (HuIFN-alpha), particularly when high multiplicities of infection are used. However, HuIFN-gamma partially inhibits HSV-1 translation in HEp-2 cells infected at low multiplicities. Under these conditions, the transcription of genes alpha 22, TK, and gamma 0 is greatly diminished. The combined addition of human tumor necrosis factor (TNF) and HuIFN-gamma to HEp-2 cells exerts a synergistic inhibition of HSV-1 translation. Cells treated with both cytokines continue synthesizing cellular proteins, even 20 h after HSV-1 infection. As little as 10 U of IFN-gamma per ml blocked HSV-1 DNA replication, provided that TNF was also present in the medium. Analyses of HSV-1 gene transcription suggest that the action of both TNF and IFN-gamma blocked a step that comes at or prior to early HSV-1 gene expression. This early step in HSV-1 replication inhibited by TNF and IFN-gamma occurs after virus attachment and entry into cells, since the internalization of radioactive HSV-1 virion particles was not blocked by the presence of the two cytokines. Therefore, we conclude that the synergistic action of TNF plus IFN-gamma affects a step in HSV-1 replication that comes after virus entry but before or at the transcription of immediate-early genes.

  13. Positive associations between infections of Toxoplasma gondii and seropositivity with Anisakis simplex in human patients suffering from chronic urticaria.

    PubMed

    Fernández-Fígares, V; Rodero, M; Valls, A; De Frutos, C; Daschner, A; Cuéllar, C

    2015-11-01

    Toxoplasma gondii is a food-borne and orofecal microorganism which produces chronic infection, and attempts have been made to prove its negative association with atopy in the context of the hygiene hypothesis. Anisakis simplex is a fish parasite associated with chronic urticaria (CU) in endemic regions. We analysed the relationship between both infectious agents in CU. We included 42 patients with chronic urticaria (18 patients with CU associated with A. simplex sensitization and 24 not sensitized CU patients). Patients were assessed for atopy by a skin prick test (SPT) against common aeroallergens and for respiratory symptoms. Anisakis simplex sensitization was assessed by SPT and specific IgE by CAP fluoro-enzyme immunoassay (CAP-FEIA). Anti-T. gondii IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). CU patients were analysed with respect to T. gondii seropositivity, A. simplex sensitization, atopy and immigrant status. The seroprevalence of T. gondii was 40.5% in CU patients and 42.1% in the control group. Immigrants were more frequently infected by T. gondii (41.2% versus 12%; P =0.036). Anti-T. gondii IgG antibodies were associated with past A. simplex parasitism (odds ratio 6.73; P =0.03) and independently with atopic sensitization (odds ratio 5.85; P =0.04). In CU patients, T. gondii has no protective effect on atopic sensitization or A. simplex sensitization.

  14. Complement Opsonization Promotes Herpes Simplex Virus 2 Infection of Human Dendritic Cells

    PubMed Central

    Ellegård, Rada; Nyström, Sofia; Rondahl, Elin; Serrander, Lena; Bergström, Tomas; Sjöwall, Christopher; Eriksson, Kristina

    2016-01-01

    ABSTRACT Herpes simplex virus 2 (HSV-2) is one of the most common sexually transmitted infections globally, with a very high prevalence in many countries. During HSV-2 infection, viral particles become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of immune responses. In genital mucosa, the primary target cells for HSV-2 infection are epithelial cells, but resident immune cells, such as dendritic cells (DCs), are also infected. DCs are the activators of the ensuing immune responses directed against HSV-2, and the aim of this study was to examine the effects opsonization of HSV-2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV-2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV-2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV-1- or HSV-2-specific antibodies more or less abolished HSV-2 infection of DCs. Our results clearly demonstrate the importance of studying HSV-2 infection under conditions that ensue in vivo, i.e., conditions under which the virions are covered in complement fragments and complement fragments and antibodies, as these shape the infection and the subsequent immune response and need to be further elucidated. IMPORTANCE During HSV-2 infection, viral particles should become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of the immune responses. The dendritic cells are activators of the immune responses directed against HSV-2, and the aim of this study was to examine the

  15. Search for inhibitors against herpes simplex virus type-I in cell extracts derived from human lymphoblastoid cell lines.

    PubMed

    Lin, K H

    1977-06-01

    Cell extracts obtained from KB cells and 5 human lymphoblastoid cell lines including 2 from Burkitt's lymphoma (P3HR-1 and Raji), one each from nasopharyngeal carcinoma (no.223), acute lymphatic leukemia (MOLT-4) and a healthy person (NC-37) were tested for their inhibitory effects on the growth of herpes simplex virus type-1 (HSV-1) in green monkey kidney (GMK) cells by the plaque titration method. The relationship between the production of HSV-1 inhibitors and the degree of Epstein-Barr virus (EBV) genome repression in lymphoblastoid cells were also examined. Among the cell lines used P3HR-1 and no.223 cells produced a few EBV particles, Raji and NC-37 cells contained EBV genomes only, and MOLT-4 as well as KB cells were EBV genome-negative. The results revealed that P3HR-1 cell extract showed a tendency to inhibit HSV-1 growth in GMK cells but the other 4 lymphoblastoid cell lines and KB cells did not produce HSV-1 inhibitors, indicating that EBV genomes governing the formation of EBV structural antigens were not related to the production of HSV-1 growth inhibitors. The extracts from MOLT-4 cells, which are only a T lymphocyte cell line used in this study, stimulated HSV-1 growth in GMK cells significantly.

  16. Etiology of acute conjunctivitis due to coxsackievirus A24 variant, human adenovirus, herpes simplex virus, and Chlamydia in Beijing, China.

    PubMed

    Li, Jie; Yang, Yongsheng; Lin, Changying; Li, Weihong; Yang, Yang; Zhang, Yong; Jia, Lei; Li, Xitai; Chen, Lijuan; Wang, Quanyi

    2014-01-01

    Acute conjunctivitis is a common disease associated with high morbidity and economic burden. To clarify the etiological characteristics of acute conjunctivitis in Beijing, surveillance of acute conjunctivitis was conducted from July to October during 2007-2012 by collecting eye swabs from patients treated at surveillance hospitals affiliated with a surveillance program of 18 districts Center for Disease Prevention and Control in Beijing. Coxsackievirus A24 variant (CA24v), enterovirus 70 (EV70), human adenovirus (HAdV), herpes simplex virus (HSV), and chlamydia were identified by PCR. Phylogenetic analysis of the VP1 region of CA24v was conducted. Comparisons of proportions and statistical significance were performed using the chi-square test. HAdV was found to be the most prevalent pathogen, followed by CA24v, chlamydia, and HSV. Significant differences in the symptoms of ocular pain, photophobia, and epiphora were identified among the 4 agents. The prevalence of HAdV- and CA24v-mediated conjunctivitis peaked in July or August and September or October, respectively. Nucleotide sequences of the VP1 regions among the isolated CA24v strains shared 92.8%-100% homology. In conclusion, HAdV followed by CA24v, chlamydia, and HSV were the most common causative agents of acute conjunctivitis in Beijing. Comprehensive, continuous surveillance and advanced laboratory techniques are needed for further studies.

  17. Efficient quiescent infection of normal human diploid fibroblasts with wild-type herpes simplex virus type 1.

    PubMed

    McMahon, Robert; Walsh, Derek

    2008-10-01

    Quiescent infection of cultured cells with herpes simplex virus type 1 (HSV-1) provides an important, amenable means of studying the molecular mechanics of a nonproductive state that mimics key aspects of in vivo latency. To date, establishing high-multiplicity nonproductive infection of human cells with wild-type HSV-1 has proven challenging. Here, we describe simple culture conditions that established a cell state in normal human diploid fibroblasts that supported efficient quiescent infection using wild-type virus and exhibited many important properties of the in vivo latent state. Despite the efficient production of immediate early (IE) proteins ICP4 and ICP22, the latter remained unprocessed, and viral late gene products were only transiently and inefficiently produced. This low level of virus activity in cultures was rapidly suppressed as the nonproductive state was established. Entry into quiescence was associated with inefficient production of the viral trans-activating protein ICP0, and the accumulation of enlarged nuclear PML structures normally dispersed during productive infection. Lytic replication was rapidly and efficiently restored by exogenous expression of HSV-1 ICP0. These findings are in agreement with previous models in which quiescence was established with HSV mutants disrupted in their expression of IE gene products that included ICP0 and, importantly, provide a means to study cellular mechanisms that repress wild-type viral functions to prevent productive replication. We discuss this model in relation to existing systems and its potential as a simple tool to study the molecular mechanisms of quiescent infection in human cells using wild-type HSV-1.

  18. Herpes Simplex Virus (HSV)

    MedlinePlus

    ... rashes clinical tools newsletter | contact Share | Herpes Simplex Virus (HSV) A parent's guide to condition and treatment ... skin or mouth sores with the herpes simplex virus (HSV) is called primary herpes. This may be ...

  19. Variability of human immunodeficiency virus-1 in the female genital reservoir during genital reactivation of herpes simplex virus type 2.

    PubMed

    LeGoff, J; Roques, P; Jenabian, M-A; Charpentier, C; Brochier, C; Bouhlal, H; Gresenguet, G; Frost, E; Pepin, J; Mayaud, P; Belec, L

    2015-09-01

    Clinical and subclinical genital herpes simplex virus type 2 (HSV-2) reactivations have been associated with increases in human immunodeficiency virus (HIV)-1 genital shedding. Whether HSV-2 shedding contributes to the selection of specific genital HIV-1 variants remains unknown. We evaluated the genetic diversity of genital and blood HIV-1 RNA and DNA in 14 HIV-1/HSV-2-co-infected women, including seven with HSV-2 genital reactivation, and seven without as controls. HIV-1 DNA and HIV-1 RNA env V1-V3 sequences in paired blood and genital samples were compared. The HSV-2 selection pressure on HIV was estimated according to the number of synonymous substitutions (dS), the number of non-synonymous substitutions (dN) and the dS/dN ratio within HIV quasi-species. HIV-1 RNA levels in cervicovaginal secretions were higher in women with HSV-2 replication than in controls (p0.02). Plasma HIV-1 RNA and genital HIV-1 RNA and DNA were genetically compartmentalized. No differences in dS, dN and the dS/dN ratio were observed between the study groups for either genital HIV-1 RNA or plasma HIV-1 RNA. In contrast, dS and dN in genital HIV-1 DNA were significantly higher in patients with HSV-2 genital reactivation (p <0.01 and p <0.05, respectively). The mean of the dS/dN ratio in genital HIV-1 DNA was slightly higher in patients with HSV-2 genital replication, indicating a trend for purifying selection (p 0.056). HSV-2 increased the genetic diversity of genital HIV-1 DNA. These observations confirm molecular interactions between HSV-2 and HIV-1 at the genital tract level. PMID:26003280

  20. Human CD8+ herpes simplex virus-specific cytotoxic T-lymphocyte clones recognize diverse virion protein antigens.

    PubMed Central

    Tigges, M A; Koelle, D; Hartog, K; Sekulovich, R E; Corey, L; Burke, R L

    1992-01-01

    The role of the HLA class I-restricted, CD8+, herpes simplex virus (HSV)-specific cytotoxic T lymphocytes (CTL) in the control of human HSV infections is controversial because previous reports suggest that a substantial portion of the antigen-specific lytic response is mediated by CD4+ cells. To address this question directly, we isolated HSV-specific CD8+ CTL clones from a patient with recurrent genital herpes. These CTL were cloned by coculturing responder peripheral blood mononuclear cells (PBMC) with phytohemagglutinin-stimulated PBMC that had been infected with live HSV-2 and then irradiated prior to the addition of responder cells. After 1 week, CTL were cloned by limiting dilution using phytohemagglutinin stimulation and allogeneic feeder PBMC. Seven clones were isolated; all seven clones were CD8+ CD4- CD3+ DRbright, six lysed only HSV-2-infected targets, and one lysed both HSV-1- and HSV-2-infected targets. Antigen presentation was restricted by two to three different HLA class I loci. To determine the antigens recognized by these HSV-specific CTL, target cells were infected with HSV in the presence of acyclovir, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, or cycloheximide in a series of drug block/release protocols to limit the repertoire of viral gene expression to select transcriptional classes. Five of the clones exhibited a different pattern of cytotoxicity, suggesting that each recognized a distinct HSV antigen. One of the clones appears to be directed against an immediate-early antigen; six of the clones recognize virion proteins. Five of these clones recognized internal virion proteins that could be introduced into target cells by HSV infection in the absence of virus gene expression. Antigen specificity was further tested by using vaccinia virus vectors that express glycoproteins gD2 and gB2 or the tegument protein VP16. One clone lysed vaccinia virus/gD2-infected target cells; the remaining clones did not recognize any of these gene

  1. Human papilloma virus, herpes simplex virus and epstein barr virus in oral squamous cell carcinoma from eight different countries.

    PubMed

    Jalouli, Jamshid; Jalouli, Miranda M; Sapkota, Dipak; Ibrahim, Salah O; Larsson, Per-Anders; Sand, Lars

    2012-02-01

    Oral squamous cell carcinoma (OSCC) is a major health problem in many parts of the world, and the major causative agents are thought to be the use of alcohol and tobacco. Oncogenic viruses have also been suggested to be involved in OSCC development. This study investigated the prevalence of human papillomaviruses (HPV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in 155 OSCC from eight different countries from different ethnic groups, continents and with different socioeconomic backgrounds. 41 A total of OSCCs were diagnosed in the tongue (26%) and 23 in the floor of the mouth (15%); the other 91 OSCCs were diagnosed in other locations (59%). The patients were also investigated regarding the use of alcohol and smoking and smokeless tobacco habits. Tissue samples were obtained from formalin-fixed, paraffin-embedded samples of the OSCC. DNA was extracted and the viral genome was examined by single, nested and semi-nested PCR assays. Sequencing of double-stranded DNA from the PCR product was carried out. Following sequencing of the HPV-, HSV- and EBV-positive PCR products, 100% homology between the sampels was found. Of all the 155 OSCCs examined, 85 (55%) were positive for EBV, 54 (35%) for HPV and 24 (15%) for HSV. The highest prevalence of HPV was seen in Sudan (65%), while HSV (55%) and EBV (80%) were most prevalent in the UK. In 34% (52/155) of all the samples examined, co-infection by two (46/155=30%) or three (6/155=4%) virus specimens was detected. The most frequent double infection was HPV with EBV in 21% (32/155) of all OSCCs. There was a statistically significant higher proportion of samples with HSV (p=0.026) and EBV (p=0.015) in industrialized countries (Sweden, Norway, UK and USA) as compared to developing countries (Sudan, India, Sri Lanka and Yemen). Furthermore, there was a statistically significant higher co-infection of HSV and EBV in samples from industrialized countries (p=0.00031). No firm conclusions could be drawn regarding the

  2. Novel Method Based on Real-Time Cell Analysis for Drug Susceptibility Testing of Herpes Simplex Virus and Human Cytomegalovirus.

    PubMed

    Piret, Jocelyne; Goyette, Nathalie; Boivin, Guy

    2016-08-01

    The plaque reduction assay (PRA) is the gold standard phenotypic method to determine herpes simplex virus (HSV) and human cytomegalovirus (HCMV) susceptibilities to antiviral drugs. However, this assay is subjective and labor intensive. Here, we describe a novel antiviral phenotypic method based on real-time cell analysis (RTCA) that measures electronic impedance over time. The effective drug concentrations that reduced by 50% (EC50s) the cytopathic effects induced by HSV-1 and HCMV were evaluated by both methods. The EC50s of acyclovir and foscarnet against a reference wild-type (WT) HSV-1 strain in Vero cells were, respectively, 0.5 μM and 32.6 μM by PRA and 0.8 μM and 93.6 μM by RTCA. The EC50 ratios for acyclovir against several HSV-1 thymidine kinase (TK) mutants were 101.8×, 73.4×, 28.8×, and 35.4× (PRA) and 18.0×, 52.0×, 5.5×, and 87.8× (RTCA) compared to those for the WT. The EC50 ratios for acyclovir and foscarnet against the HSV-1 TK/DNA polymerase mutant were 182.8× and 9.7× (PRA) and >125.0× and 10.8× (RTCA) compared to the WT. The EC50s of ganciclovir and foscarnet against WT HCMV strain AD169 in fibroblasts were, respectively, 1.6 μM and 27.8 μM by PRA and 5.0 μM and 111.4 μM by RTCA. The EC50 ratios of ganciclovir against the HCMV UL97 mutant were 3.8× (PRA) and 8.2× (RTCA) compared to those for the WT. The EC50 ratios of ganciclovir and foscarnet against the HCMV UL97/DNA polymerase mutant were 17.1× and 12.1× (PRA) and 14.7× and 4.6× (RTCA) compared to those for the WT. RTCA allows objective drug susceptibility testing of HSV and HCMV and could permit high-throughput screening of new antivirals. PMID:27252463

  3. Titration of herpes simplex virus antibodies in human sera by the enzyme-linked immunosorbent assay (ELISA).

    PubMed

    Vestergaard, B F; Grauballe, P C; Spanggaard, H

    1977-12-01

    100 sera from healthy adults were titrated simultaneously for herpes simplex virus (HSV) antibodies by ELISA and neutralization. The ELISA was performed on microtitre plates where approximately 100 ng of detergent solubilized and chromatographically purified HSV glycoproteins was bound covalently to the plastic bottom of each well. The optical density (OD) values obtained by the use of the peroxidase-1.2phenylendiamindihydrochloride system showed good correlation with the neuratlizing antibody titres. Sera with very low neutralizing titres were clearly positive in ELISA.

  4. Recombinant adeno-associated virus-mediated high-efficiency, transient expression of the murine cationic amino acid transporter (ecotropic retroviral receptor) permits stable transduction of human HeLa cells by ecotropic retroviral vectors.

    PubMed Central

    Bertran, J; Miller, J L; Yang, Y; Fenimore-Justman, A; Rueda, F; Vanin, E F; Nienhuis, A W

    1996-01-01

    Adeno-associated virus has a broad host range, is nonpathogenic, and integrates into a preferred location on chromosome 19, features that have fostered development of recombinant adeno-associated viruses (rAAV) as gene transfer vectors for therapeutic applications. We have used an rAAV to transfer and express the murine cationic amino acid transporter which functions as the ecotropic retroviral receptor, thereby rendering human cells conditionally susceptible to infection by an ecotropic retroviral vector. The proportion of human HeLa cells expressing the receptor at 60 h varied as a function of the multiplicity of infection (MOI) with the rAAV. Cells expressing the ecotropic receptor were efficiently transduced with an ecotropic retroviral vector encoding a nucleus-localized form of beta-galactosidase. Cells coexpressing the ecotropic receptor and nucleus-localized beta-galactosidase were isolated by fluorescence-activated cell sorting, and cell lines were recovered by cloning at limiting dilution. After growth in culture, all clones contained the retroviral vector genome, but fewer than 10% (3 of 47) contained the rAAV genome and continued to express the ecotropic receptor. The ecotropic receptor coding sequences in the rAAV genome were under the control of a tetracycline-modulated promoter. In the presence of tetracycline, receptor expression was low and the proportion of cells transduced by the ecotropic retroviral vector was decreased. Modulation of receptor expression was achieved with both an episomal and an integrated form of the rAAV genome. These data establish that functional gene expression from an rAAV genome can occur transiently without genome integration. PMID:8794313

  5. Characterisation of potential novel allergens in the fish parasite Anisakis simplex

    PubMed Central

    Fæste, Christiane Kruse; Jonscher, Karen R.; Dooper, Maaike M.W.B.; Egge-Jacobsen, Wolfgang; Moen, Anders; Daschner, Alvaro; Egaas, Eliann; Christians, Uwe

    2016-01-01

    The parasitic nematode Anisakis simplex occurs in fish stocks in temperate seas. A. simplex contamination of fish products is unsavoury and a health concern considering human infection with live larvae (anisakiasis) and allergic reactions to anisakid proteins in seafood. Protein extracts of A. simplex produce complex band patterns in gel electrophoresis and IgE-immunostaining. In the present study potential allergens have been characterised using sera from A. simplex-sensitised patients and proteome data obtained by mass spectrometry. A. simplex proteins were homologous to allergens in other nematodes, insects, and shellfish indicating cross-reactivity. Characteristic marker peptides for relevant A. simplex proteins were described. PMID:27110489

  6. [Design of a curve model for the detection of human immunoglobulin G against herpes simplex virus in ultramicroELISA from a single serum dilution].

    PubMed

    Angeles Ribas, M A; Otero, A; Alvarez, M; Marrero, M; Vázquez, S

    1994-01-01

    The use of a curve model in the application of a ultramicroELISA technique for the detection of human immunoglobulin G against herpes simplex virus is reported. Based on end point titration (linear regression) of 100 initial sera, 51 of these, with r2 > 0.98, were selected, and 4 curve models were elaborated to relate the natural fluorescence logarithm for 4 dilutions with the previously determined natural end point titration logarithm. The curve corresponding to the 1:40 (r2 = 0.9645) was selected to evaluate 39 additional serum samples whose approximate titration was known through the graphic design of the 4 dilutions. An 89% coincidence was found regarding the latter. Divergence of the other 11% was due to the lack of accuracy of the graphic method in the points near the cutline.

  7. Herpes simplex virus type 1-induced FasL expression in human monocytic cells and its implications for cell death, viral replication, and immune evasion.

    PubMed

    Iannello, Alexandre; Debbeche, Olfa; El Arabi, Raoudha; Samarani, Suzanne; Hamel, David; Rozenberg, Flore; Heveker, Nikolaus; Ahmad, Ali

    2011-02-01

    Herpes simplex virus type 1 (HSV-1) is a ubiquitously occurring pathogen that infects humans early in childhood. The virus persists as a latent infection in dorsal root ganglia, especially of the trigeminal nerve, and frequently becomes reactivated in humans under conditions of stress. Monocytic cells constitute an important component of the innate and adaptive immune responses. We show here for the first time that HSV-1 stimulates human FasL promoter and induces de novo expression of FasL on the surface of human monocytic cells, including monocytes and macrophages. This virus-induced FasL expression causes death of monocytic cells growing in suspension, but not in monolayers (e.g., macrophages). The addition of a broad-spectrum caspase inhibitor, as well as anti-FasL antibodies, reduced cell death but increased viral replication in the virus-infected cell cultures. We also show here for the first time that the virus-induced de novo expression of FasL on the cell surface acts as an immune evasion mechanism by causing the death of interacting human CD4+ T cells, CD8+ T cells, and natural killer (NK) cells. Our study provides novel insights on FasL expression and cell death in HSV-infected human monocytic cells and their impact on interacting immune cells.

  8. Herpes simplex encephalitis (HSE) and the immunocompromised: a clinical and autopsy study of HSE in the settings of cancer and human immunodeficiency virus-type 1 infection.

    PubMed

    Schiff, D; Rosenblum, M K

    1998-03-01

    Although herpes simplex encephalitis (HSE) is not regarded as an opportunistic infection, the occurrence of HSE in immunocompromised patients has been documented and the suggestion made that unusual clinical and neuropathologic features characterize the disorder in this population. To further characterize HSE as it affects the immunodeficient, the authors reviewed the clinical and pathological findings in three immunocompromised patients with autopsy-proven HSE. Two patients had cancer (one with lymphoma and another with glioblastoma multiforme), one was known to be human immunodeficiency virus-type 1 (HIV-1)-seropositive and a second was suspected of harboring underlying HIV-1 infection. Two were receiving dexamethasone at onset of HSE. All had fever, mental status changes and new, focal neurological deficits or worsening of established deficits. Cerebrospinal fluid (CSF) pleocytosis was absent or minimal and head computerized tomographic (CT) scans, performed in all cases, were unrevealing. No patient was clinically suspected of having HSE, only one received acyclovir (for concurrent mucocutaneous herpes) and HSE played a major role in all deaths. Autopsy revealed an unusual form of HSE characterized by a noninflammatory, pseudoischemic histological presentation and the unexpected persistence of viral antigens in abundance despite survival beyond the clinical stage during which inflammatory responses usually peak and productive brain infection wanes. The incidence of HSE in the immunocompromised may be underestimated. Preexistent neurological disease, a noninflammatory CSF profile and negative CT scan may confound the diagnosis in this population, a typical clinical presentation notwithstanding. Increased clinical suspicion, the use of magnetic resonance imaging and polymerase chain reaction analysis of CSF for herpes simplex virus nucleic acid sequences may permit more rapid diagnosis and treatment. The absence of inflammatory infiltrates in some fatal cases of

  9. A hybrid herpesvirus infectious vector based on Epstein-Barr virus and herpes simplex virus type 1 for gene transfer into human cells in vitro and in vivo.

    PubMed

    Wang, S; Vos, J M

    1996-12-01

    We have developed a miniviral vector, pH300, based on the human herpesviruses 1 and 4, herpes simplex virus type 1 (HSV-1), and Epstein-Barr virus (EBV), carrying EBV sequences for plasmid episomal maintenance and HSV-1 sequences for amplification and packaging in multimeric form into HSV-1 capsids in the presence of a helper virus and helper cell line. A reporter gene, the bacterial lacZ gene, which expressed beta-galactosidase, was inserted into the multiple cloning site of pH300 to make pH300-lac. The packaged pH300-lac DNA was very efficient in infecting human cells in tissue culture. The pH300-lac miniviral stock was used to infect in vitro various human cell types derived from breast cancer, lung cancer, and liver cancer. Up to 95% of cells were infected and expressed beta-galactosidase activity after exposure to viral stock at a multiplicity of infection of 3. There was essentially no apparent cytotoxicity after infection of cultured cells in vitro. To test in vivo gene delivery, human liver tumor cells preimplanted subcutaneously in nude mice and injected in situ with pH300-lac showed high efficiency of ectopic gene expression. The pH300 miniviral vector is a simple and effective gene transfer system which shows potential for gene therapy of cancer and inherited diseases.

  10. Herpes simplex virus type 2 virion host shutoff protein suppresses innate dsRNA antiviral pathways in human vaginal epithelial cells.

    PubMed

    Yao, Xiao-Dan; Rosenthal, Kenneth Lee

    2011-09-01

    Viruses that establish persistent infections have evolved numerous strategies to evade host innate antiviral responses. We functionally assessed the role of herpes simplex virus type 2 (HSV-2) virion host shutoff (vhs) protein on innate immune sensing pathways in human vaginal epithelial cells (VK2 ECs). Infection of cells with wild-type (WT) HSV-2 significantly decreased expression of innate immune sensors of viral infection, Toll-like receptor (TLR)2, TLR3, retinoic acid inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda-5), relative to cells infected with a mutant that lacks vhs (vhsB) or mock-infected cells. Transfection with HSV-2 vhs similarly decreased expression of TLR2, TLR3, RIG-I and Mda-5, which was also confirmed in human embryonic kidney (HEK) 293 cells. vhsB infection of VK2 cells caused robust increases in the active form of interferon regulatory factor (IRF)3 and its translocation to the nucleus compared with the WT. Additionally, IRF3 activation by Sendai virus and polyinosinic : polycytidylic acid-induced stimulation of beta interferon (IFN-β) was significantly inhibited in vhs-transfected cells. Overall, our findings provide the first evidence that HSV-2 vhs plays roles in selectively inhibiting TLR3 and RIG-I/Mda-5, as well as TLR2-mediated antiviral pathways for sensing dsRNA and effectively suppresses IFN-β antiviral responses in human vaginal ECs.

  11. An efficient deletion mutant packaging system for defective herpes simplex virus vectors: Potential applications to human gene therapy and neuronal physiology

    SciTech Connect

    Geller, A.I.; Keyomarsi, K.; Bryan, J.; Pardee, A.B. )

    1990-11-01

    The authors have previously described a defective herpes simplex virus (HSV-1) vector system that permits that introduction of virtually any gene into nonmitotic cells. pHSVlac, the prototype vector, stably expresses Escherichia coli {beta}-galactosidase from a constitutive promoter in many human cell lines, in cultured rat neurons from throughout the nervous system, and in cells in the adult rat brain. HSV-1 vectors expressing other genes may prove useful for studying neuronal physiology or performing human gene therapy for neurological diseases, such as Parkinson disease or brain tumors. A HSV-1 temperature-sensitive (ts) mutant, ts K, has been used as helper virus; ts mutants revert to wild type. In contrast, HSV-1 deletion mutants essentially cannot revert to wild type; therefore, use of a deletion mutant as helper virus might permit human gene therapy with HSV-1 vectors. They now report an efficient packaging system for HSV-1 VECTORS USING A DELETION MUTANT, d30EBA, as helper virus; virus is grown on the complementing cell line M64A. pHSVlac virus prepared using the deletion mutant packaging system stably expresses {beta}-galactosidase in cultured rat sympathetic neurons and glia. Both D30EBA and ts K contain a mutation in the IE3 gene of HSV-1 strain 17 and have the same phenotype; therefore, changing the helper virus from ts K to D30EBA does not alter the host range or other properties of the HSV-1 vector system.

  12. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus

    SciTech Connect

    Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.

    1986-07-15

    The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells.

  13. Herpes simplex virus and cytomegalovirus co-infection presenting as exuberant genital ulcer in a woman infected with human immunodeficiency virus.

    PubMed

    Gouveia, A I; Borges-Costa, J; Soares-Almeida, L; Sacramento-Marques, M; Kutzner, H

    2014-12-01

    In patients infected with human immunodeficiency virus (HIV), genital herpes can result in severe and atypical clinical presentations, and can become resistant to aciclovir treatment. Rarely, these manifestations may represent concurrent herpes simplex virus (HSV) with other agents. We report a 41-year-old black woman with HIV who presented with extensive and painful ulceration of the genitalia. Histological examination of a biopsy sample was suggestive of herpetic infection, and intravenous aciclovir was started, but produced only partial improvement. PCR was performed on the biopsy sample, and both HSV and cytomegalovirus (CMV) DNA was detected. Oral valganciclovir was started with therapeutic success. CMV infection is common in patients infected with HIV, but its presence in mucocutaneous lesions is rarely reported. This case exemplifies the difficulties of diagnosis of genital ulcers in patients infected with HIV. The presence of exuberant and persistent HSV genital ulcers in patients with HIV should also raise suspicions of the presence of co-infection with other organisms such as CMV.

  14. Different presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii in schizophrenia: meta-analysis and analytical study

    PubMed Central

    Gutiérrez-Fernández, José; Luna del Castillo, Juan de Dios; Mañanes-González, Sara; Carrillo-Ávila, José Antonio; Gutiérrez, Blanca; Cervilla, Jorge A; Sorlózano-Puerto, Antonio

    2015-01-01

    In the present study we have performed both a meta-analysis and an analytical study exploring the presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii antibodies in a sample of 143 schizophrenic patients and 143 control subjects. The meta-analysis was performed on papers published up to April 2014. The presence of serum immunoglobulin G and immunoglobulin A was performed by enzyme-linked immunosorbent assay test. The detection of microbial DNA in total peripheral blood was performed by nested polymerase chain reaction. The meta-analysis showed that: 1) C. pneumoniae DNA in blood and brain are more common in schizophrenic patients; 2) there is association with parasitism by T. gondii, despite the existence of publication bias; and 3) herpes viruses were not more common in schizophrenic patients. In our sample only anti-Toxoplasma immunoglobulin G was more prevalent and may be a risk factor related to schizophrenia, with potential value for prevention. PMID:25848282

  15. Pretreatment of human cervicovaginal mucus with pluronic F127 enhances nanoparticle penetration without compromising mucus barrier properties to herpes simplex virus.

    PubMed

    Ensign, Laura M; Lai, Samuel K; Wang, Ying-Ying; Yang, Ming; Mert, Olcay; Hanes, Justin; Cone, Richard

    2014-12-01

    Mucosal drug delivery nanotechnologies are limited by the mucus barrier that protects nearly all epithelial surfaces not covered with skin. Most polymeric nanoparticles, including polystyrene nanoparticles (PS), strongly adhere to mucus, thereby limiting penetration and facilitating rapid clearance from the body. Here, we demonstrate that PS rapidly penetrate human cervicovaginal mucus (CVM), if the CVM has been pretreated with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large polyethylene glycol (PEG)-coated, nonmucoadhesive nanoparticles (PS-PEG) did not change in F127-pretreated CVM, implying that F127 did not significantly alter the native pore structure of CVM. Additionally, herpes simplex virus type 1 (HSV-1) remains adherent in F127-pretreated CVM, indicating that the presence of F127 did not reduce adhesive interactions between CVM and the virions. In contrast to treatment with a surfactant that has been approved for vaginal use as a spermicide (nonoxynol-9 or N9), there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for 1 week. Pluronic F127 pretreatment holds potential as a method to safely improve the distribution, retention, and efficacy of nanoparticle formulations without compromising CVM barrier properties to pathogens. PMID:25347518

  16. Pretreatment of Human Cervicovaginal Mucus with Pluronic F127 Enhances Nanoparticle Penetration without Compromising Mucus Barrier Properties to Herpes Simplex Virus

    PubMed Central

    2015-01-01

    Mucosal drug delivery nanotechnologies are limited by the mucus barrier that protects nearly all epithelial surfaces not covered with skin. Most polymeric nanoparticles, including polystyrene nanoparticles (PS), strongly adhere to mucus, thereby limiting penetration and facilitating rapid clearance from the body. Here, we demonstrate that PS rapidly penetrate human cervicovaginal mucus (CVM), if the CVM has been pretreated with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large polyethylene glycol (PEG)-coated, nonmucoadhesive nanoparticles (PS–PEG) did not change in F127-pretreated CVM, implying that F127 did not significantly alter the native pore structure of CVM. Additionally, herpes simplex virus type 1 (HSV-1) remains adherent in F127-pretreated CVM, indicating that the presence of F127 did not reduce adhesive interactions between CVM and the virions. In contrast to treatment with a surfactant that has been approved for vaginal use as a spermicide (nonoxynol-9 or N9), there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for 1 week. Pluronic F127 pretreatment holds potential as a method to safely improve the distribution, retention, and efficacy of nanoparticle formulations without compromising CVM barrier properties to pathogens. PMID:25347518

  17. Tissue-Specific Expression of Herpes Simplex Virus Thymidine Kinase Gene Delivered by Adeno-Associated Virus Inhibits the Growth of Human Hepatocellular Carcinoma in Athymic Mice

    NASA Astrophysics Data System (ADS)

    Su, Hua; Lu, Ronghua; Chang, Judy C.; Kan, Yuet Wai

    1997-12-01

    About 70% of hepatocellular carcinomas are known to express α -fetoprotein, which is normally expressed in fetal but not in adult livers. To induce herpes simplex virus-thymidine kinase expression in these cancer cells, we constructed an adeno-associated viral vector containing the HSV-TK gene under the control of the α -fetoprotein enhancer and albumin promoter. We previously demonstrated in vitro that although this vector can transduce a variety of human cells, only transduced AFP and albumin-expressing hepatocellular carcinoma cell lines were sensitive to killing by ganciclovir (GCV). In the present study, we explored the effect of this vector on hepatocellular carcinoma cells in vivo. Subcutaneous tumors generated in nude mice by implanting hepatocellular carcinoma cells previously transduced with this vector shrank dramatically after treatment with GCV. Bystander effect was also observed on the tumors generated by mixing transduced and untransduced cells. To test whether the tumor cells can be transduced by the virus in vivo, we injected the recombinant adeno-associated virus into tumors generated by untransduced hepatocarcinoma cell line. Tumor growth were retarded after treatment with GCV. These experiments demonstrate the feasibility of in vivo transduction of tumor cell with rAAV.

  18. Short communication: a repeated simian human immunodeficiency virus reverse transcriptase/herpes simplex virus type 2 cochallenge macaque model for the evaluation of microbicides.

    PubMed

    Kenney, Jessica; Derby, Nina; Aravantinou, Meropi; Kleinbeck, Kyle; Frank, Ines; Gettie, Agegnehu; Grasperge, Brooke; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Zydowsky, Thomas M; Robbiani, Melissa

    2014-11-01

    Epidemiological studies suggest that prevalent herpes simplex virus type 2 (HSV-2) infection increases the risk of HIV acquisition, underscoring the need to develop coinfection models to evaluate promising prevention strategies. We previously established a single high-dose vaginal coinfection model of simian human immunodeficiency virus (SHIV)/HSV-2 in Depo-Provera (DP)-treated macaques. However, this model does not appropriately mimic women's exposure. Repeated limiting dose SHIV challenge models are now used routinely to test prevention strategies, yet, at present, there are no reports of a repeated limiting dose cochallenge model in which to evaluate products targeting HIV and HSV-2. Herein, we show that 20 weekly cochallenges with 2-50 TCID50 simian human immunodeficiency virus reverse transcriptase (SHIV-RT) and 10(7) pfu HSV-2 results in infection with both viruses (4/6 SHIV-RT, 6/6 HSV-2). The frequency and level of vaginal HSV-2 shedding were significantly greater in the repeated exposure model compared to the single high-dose model (p<0.0001). We used this new model to test the Council's on-demand microbicide gel, MZC, which is active against SHIV-RT in DP-treated macaques and HSV-2 and human papillomavirus (HPV) in mice. While MZC reduced SHIV and HSV-2 infections in our repeated limiting dose model when cochallenging 8 h after each gel application, a barrier effect of carrageenan (CG) that was not seen in DP-treated animals precluded evaluation of the significance of the antiviral activity of MZC. Both MZC and CG significantly (p<0.0001) reduced the frequency and level of vaginal HSV-2 shedding compared to no gel treatment. This validates the use of this repeated limiting dose cochallenge model for testing products targeting HIV and HSV-2.

  19. Members of 3-O-Sulfotransferases (3-OST) Family: A Valuable Tool from Zebrafish to Humans for Understanding Herpes Simplex Virus Entry.

    PubMed

    Baldwin, John; Shukla, Deepak; Tiwari, Vaibhav

    2013-01-01

    The journey of many viruses to infect cells begins when the virus first binds to cell surface heparan sulfate (HS). The initial step of cell attachment or binding during herpes simplex virus type-1 (HSV-1) entry is mediated by envelope glycoprotein B (gB) and C (gC). The binding is followed by fusion between virus envelope and cell membrane during which HSV-1 glycoprotein D (gD) interacts with a modified form of HS know as 3-O-sulfated heparan sulfate (3-OS HS). The rare modification of 3-O-sulfation on HS chain is governed by enzymes known as 3-O-sulfotransferase (3-OST). Currently, there are seven isoforms of human 3-OSTs that have been identified, and with the exception of 3-OST-1, all other 3-OST isoforms allow HSV-1 entry and spread. Recently, the product of the zebrafish (ZF)-encoded 3-OST-3 was also recognized as a gD receptor, which mediates HSV-1 entry and cell-cell fusion similar to human 3-OST-3. Interestingly, the ZF system expresses multiple isoforms of 3-OST which could be very useful for studying the involvement of HS and 3-OS HS in virus tropism and virus-induced inflammation. In addition, therapeutic targeting of 3-OST generated HS is likely to bring about novel interventions against HSV-1. In this review we have taken a closer look at the potential of both human and ZF encoded 3-OSTs as valuable tools in HSV entry and inflammation studies.

  20. Short Communication: A Repeated Simian Human Immunodeficiency Virus Reverse Transcriptase/Herpes Simplex Virus Type 2 Cochallenge Macaque Model for the Evaluation of Microbicides

    PubMed Central

    Kenney, Jessica; Derby, Nina; Aravantinou, Meropi; Kleinbeck, Kyle; Frank, Ines; Gettie, Agegnehu; Grasperge, Brooke; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Zydowsky, Thomas M.

    2014-01-01

    Abstract Epidemiological studies suggest that prevalent herpes simplex virus type 2 (HSV-2) infection increases the risk of HIV acquisition, underscoring the need to develop coinfection models to evaluate promising prevention strategies. We previously established a single high-dose vaginal coinfection model of simian human immunodeficiency virus (SHIV)/HSV-2 in Depo-Provera (DP)-treated macaques. However, this model does not appropriately mimic women's exposure. Repeated limiting dose SHIV challenge models are now used routinely to test prevention strategies, yet, at present, there are no reports of a repeated limiting dose cochallenge model in which to evaluate products targeting HIV and HSV-2. Herein, we show that 20 weekly cochallenges with 2–50 TCID50 simian human immunodeficiency virus reverse transcriptase (SHIV-RT) and 107 pfu HSV-2 results in infection with both viruses (4/6 SHIV-RT, 6/6 HSV-2). The frequency and level of vaginal HSV-2 shedding were significantly greater in the repeated exposure model compared to the single high-dose model (p<0.0001). We used this new model to test the Council's on-demand microbicide gel, MZC, which is active against SHIV-RT in DP-treated macaques and HSV-2 and human papillomavirus (HPV) in mice. While MZC reduced SHIV and HSV-2 infections in our repeated limiting dose model when cochallenging 8 h after each gel application, a barrier effect of carrageenan (CG) that was not seen in DP-treated animals precluded evaluation of the significance of the antiviral activity of MZC. Both MZC and CG significantly (p<0.0001) reduced the frequency and level of vaginal HSV-2 shedding compared to no gel treatment. This validates the use of this repeated limiting dose cochallenge model for testing products targeting HIV and HSV-2. PMID:25354024

  1. Ultrastructural Visualization of Individual Tegument Protein Dissociation during Entry of Herpes Simplex Virus 1 into Human and Rat Dorsal Root Ganglion Neurons

    PubMed Central

    Aggarwal, Anupriya; Boadle, Ross A.; Kelly, Barbara J.; Diefenbach, Russell J.; Alam, Waafiqa; Cunningham, Anthony L.

    2012-01-01

    Herpes simplex virus 1 (HSV-1) enters neurons primarily by fusion of the viral envelope with the host cell plasma membrane, leading to the release of the capsid into the cytosol. The capsid travels via microtubule-mediated retrograde transport to the nuclear membrane, where the viral DNA is released for replication in the nucleus. In the present study, the composition and kinetics of incoming HSV-1 capsids during entry and retrograde transport in axons of human fetal and dissociated rat dorsal root ganglia (DRG) neurons were examined by wide-field deconvolution microscopy and transmission immunoelectron microscopy (TIEM). We show that HSV-1 tegument proteins, including VP16, VP22, most pUL37, and some pUL36, dissociated from the incoming virions. The inner tegument proteins, including pUL36 and some pUL37, remained associated with the capsid during virus entry and transit to the nucleus in the neuronal cell body. By TIEM, a progressive loss of tegument proteins, including VP16, VP22, most pUL37, and some pUL36, was observed, with most of the tegument dissociating at the plasma membrane of the axons and the neuronal cell body. Further dissociation occurred within the axons and the cytosol as the capsids moved to the nucleus, resulting in the release of free tegument proteins, especially VP16, VP22, pUL37, and some pUL36, into the cytosol. This study elucidates ultrastructurally the composition of HSV-1 capsids that encounter the microtubules in the core of human axons and the complement of free tegument proteins released into the cytosol during virus entry. PMID:22457528

  2. Virus-mediated FCC iron nanoparticle induced synthesis of uranium dioxide nanocrystals.

    PubMed

    Ling, Tao; Yu, Huimin; Shen, Zhongyao; Wang, Hui; Zhu, Jing

    2008-03-19

    A reducing system involving M13 virus-mediated FCC Fe nanoparticles was employed to achieve uranium reduction and synthesize uranium dioxide nanocrystals. Here we show that metastable face-centered cubic (FCC) Fe nanoparticles were fabricated around the surface of the M13 virus during the specific adsorption of the virus towards Fe ions under a reduced environment. The FCC phase of these Fe nanoparticles was confirmed by careful TEM characterization. Moreover, this virus-mediated FCC Fe nanoparticle system successfully reduced contaminable U(VI) into UO(2) crystals with diameters of 2-5 nm by a green and convenient route.

  3. A modified zinc acetate gel, a potential nonantiretroviral microbicide, is safe and effective against simian-human immunodeficiency virus and herpes simplex virus 2 infection in vivo.

    PubMed

    Kenney, Jessica; Rodríguez, Aixa; Kizima, Larisa; Seidor, Samantha; Menon, Radhika; Jean-Pierre, Ninochka; Pugach, Pavel; Levendosky, Keith; Derby, Nina; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Paglini, Gabriela; Zydowsky, Thomas M; Robbiani, Melissa; Fernández Romero, José A

    2013-08-01

    We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2. PMID:23752515

  4. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    SciTech Connect

    Torpey, D.J. III

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with /sup 51/Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant.

  5. Interaction studies of the human and Arabidopsis thaliana Med25-ACID proteins with the herpes simplex virus VP16- and plant-specific Dreb2a transcription factors.

    PubMed

    Aguilar, Ximena; Blomberg, Jeanette; Brännström, Kristoffer; Olofsson, Anders; Schleucher, Jürgen; Björklund, Stefan

    2014-01-01

    Mediator is an evolutionary conserved multi-protein complex present in all eukaryotes. It functions as a transcriptional co-regulator by conveying signals from activators and repressors to the RNA polymerase II transcription machinery. The Arabidopsis thaliana Med25 (aMed25) ACtivation Interaction Domain (ACID) interacts with the Dreb2a activator which is involved in plant stress response pathways, while Human Med25-ACID (hMed25) interacts with the herpes simplex virus VP16 activator. Despite low sequence similarity, hMed25-ACID also interacts with the plant-specific Dreb2a transcriptional activator protein. We have used GST pull-down-, surface plasmon resonance-, isothermal titration calorimetry and NMR chemical shift experiments to characterize interactions between Dreb2a and VP16, with the hMed25 and aMed25-ACIDs. We found that VP16 interacts with aMed25-ACID with similar affinity as with hMed25-ACID and that the binding surface on aMed25-ACID overlaps with the binding site for Dreb2a. We also show that the Dreb2a interaction region in hMed25-ACID overlaps with the earlier reported VP16 binding site. In addition, we show that hMed25-ACID/Dreb2a and aMed25-ACID/Dreb2a display similar binding affinities but different binding energetics. Our results therefore indicate that interaction between transcriptional regulators and their target proteins in Mediator are less dependent on the primary sequences in the interaction domains but that these domains fold into similar structures upon interaction.

  6. Detection of cytomegalovirus, human parvovirus B19, and herpes simplex virus-1/2 in women with first-trimester spontaneous abortions.

    PubMed

    Zhou, Ya; Bian, Guohui; Zhou, Qiongxiu; Gao, Zhan; Liao, Pu; Liu, Yu; He, Miao

    2015-10-01

    The relationship between viral infections and first-trimester spontaneous abortions is not well-understood. The study aim was to investigate the prevalence of cytomegalovirus (CMV), human parvovirus B19 (B19V), and herpes simplex virus-1/2 (HSV-1/2) infection by molecular and serological techniques in women experiencing spontaneous miscarriage in the first trimester of pregnancy. Plasma samples were examined for CMV, B19V, and HSV-1/2 DNA using real-time quantitative polymerase chain reaction (Real-time qPCR), and for specific IgG antibodies against B19V, CMV, and HSV-1/2 using serological assays. The abortion group consisted of women (n = 1,716) with a history of two or more first-trimester spontaneous abortions. Women younger than 30 years possess higher portion to experience spontaneous abortion. No specimens were positive for B19V or CMV DNA. Seven out of the 1,716 specimens were positive for HSV-1/2 DNA. By serology, 47.24% of patients were positive for B19V IgG, 39.66% for HSV IgG, 79.31% for CMV IgG, and 9.31% for B19V IgM. The high rate of positivity for CMV IgG suggests that the majority of women with first-trimester spontaneous abortions are not susceptible to primary CMV infection. The lack of virus DNA in the majority of cases indicates that B19V, CMV, and HSV-1/2 infection is not commonly associated with first-trimester spontaneous abortion.

  7. APP processing induced by herpes simplex virus type 1 (HSV-1) yields several APP fragments in human and rat neuronal cells.

    PubMed

    De Chiara, Giovanna; Marcocci, Maria Elena; Civitelli, Livia; Argnani, Rafaela; Piacentini, Roberto; Ripoli, Cristian; Manservigi, Roberto; Grassi, Claudio; Garaci, Enrico; Palamara, Anna Teresa

    2010-11-15

    Lifelong latent infections of the trigeminal ganglion by the neurotropic herpes simplex virus type 1 (HSV-1) are characterized by periodic reactivation. During these episodes, newly produced virions may also reach the central nervous system (CNS), causing productive but generally asymptomatic infections. Epidemiological and experimental findings suggest that HSV-1 might contribute to the pathogenesis of Alzheimer's disease (AD). This multifactorial neurodegenerative disorder is related to an overproduction of amyloid beta (Aβ) and other neurotoxic peptides, which occurs during amyloidogenic endoproteolytic processing of the transmembrane amyloid precursor protein (APP). The aim of our study was to identify the effects of productive HSV-1 infection on APP processing in neuronal cells. We found that infection of SH-SY5Y human neuroblastoma cells and rat cortical neurons is followed by multiple cleavages of APP, which result in the intra- and/or extra-cellular accumulation of various neurotoxic species. These include: i) APP fragments (APP-Fs) of 35 and 45 kDa (APP-F35 and APP-F45) that comprise portions of Aβ; ii) N-terminal APP-Fs that are secreted; iii) intracellular C-terminal APP-Fs; and iv) Aβ(1-40) and Aβ(1-42). Western blot analysis of infected-cell lysates treated with formic acid suggests that APP-F35 may be an Aβ oligomer. The multiple cleavages of APP that occur in infected cells are produced in part by known components of the amyloidogenic APP processing pathway, i.e., host-cell β-secretase, γ-secretase, and caspase-3-like enzymes. These findings demonstrate that HSV-1 infection of neuronal cells can generate multiple APP fragments with well-documented neurotoxic potentials. It is tempting to speculate that intra- and extracellular accumulation of these species in the CNS resulting from repeated HSV-1 reactivation could, in the presence of other risk factors, play a co-factorial role in the development of AD.

  8. [Ocular hypertension in herpes simplex keratouveitis].

    PubMed

    Burcea, M; Avram, Corina-Ioana; Stamate, Alina-Cristina; Malciolu, R; Oprea, S; Zemba, M

    2014-01-01

    The herpes simplex virus is one of the most common pathogens in humans, who are seropositive for the virus in 90% of the cases at the adult age. It determines reccurent infections in more than a third of the population and these infections depend on the immune response of the host. Ocular infections of newborns are due to the herpes simplex virus type 2, meanwhile type 1 is found predominantly at adults; almost all ocular structures can be affected. HSV-1 in the most frequent etiologic agent in infectious anterior uveitis (with the varicelo-zosterian virus) and it is responsible for 6-10% of all cases of anterior uveitis. More than half of the keratouveitides due to HSV will develop intraocular hypertension and open-angle secondary glaucoma, during reccurences and most of them will resolve after proper control of inflammation.

  9. Stimulation of the Replication of ICP0-Null Mutant Herpes Simplex Virus 1 and pp71-Deficient Human Cytomegalovirus by Epstein-Barr Virus Tegument Protein BNRF1

    PubMed Central

    Lu, Yongxu; Orr, Anne

    2016-01-01

    ABSTRACT It is now well established that several cellular proteins that are components of promyelocytic leukemia nuclear bodies (PML NBs, also known as ND10) have restrictive effects on herpesvirus infections that are countered by viral proteins that are either present in the virion particle or are expressed during the earliest stages of infection. For example, herpes simplex virus 1 (HSV-1) immediate early (IE) protein ICP0 overcomes the restrictive effects of PML-NB components PML, Sp100, hDaxx, and ATRX while human cytomegalovirus (HCMV) IE protein IE1 targets PML and Sp100, and its tegument protein pp71 targets hDaxx and ATRX. The functions of these viral regulatory proteins are in part interchangeable; thus, both IE1 and pp71 stimulate the replication of ICP0-null mutant HSV-1, while ICP0 increases plaque formation by pp71-deficient HCMV. Here, we extend these studies by examining proteins that are expressed by Epstein-Barr virus (EBV). We report that EBV tegument protein BNRF1, discovered by other investigators to target the hDaxx/ATRX complex, increases the replication of both ICP0-null mutant HSV-1 and pp71-deficient HCMV. In addition, EBV protein EBNA-LP, which targets Sp100, also augments ICP0-null mutant HSV-1 replication. The combination of these two EBV regulatory proteins had a greater effect than each one individually. These findings reinforce the concept that disruption of the functions of PML-NB proteins is important for efficient herpesvirus infections. IMPORTANCE Whether a herpesvirus initiates a lytic infection in a host cell or establishes quiescence or latency is influenced by events that occur soon after the viral genome has entered the host cell nucleus. Certain cellular proteins respond in a restrictive manner to the invading pathogen's DNA, while viral functions are expressed that counteract the cell-mediated repression. One aspect of cellular restriction of herpesvirus infections is mediated by components of nuclear structures known as

  10. Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors

    PubMed Central

    Lai, Zhennan; Han, Ina; Zirzow, Gregory; Brady, Roscoe O.; Reiser, Jakob

    2000-01-01

    Effective gene therapy depends on the efficient transfer of therapeutic genes and their protein products to target cells. Lentiviral vectors appear promising for virus-mediated gene delivery and long-term expression in nondividing cells. The herpes simplex virus type 1 tegument protein VP22 has recently been shown to mediate intercellular transport of proteins, raising the possibility that it may be helpful in a setting where the global delivery of therapeutic proteins is desired. To investigate the effectiveness of lentiviral vectors to deliver genes encoding proteins fused to VP22, and to test whether the system is sufficiently potent to allow protein delivery from transduced cells in vitro and in vivo, fusion constructs of VP22 and the enhanced green fluorescent protein (EGFP) were prepared and delivered into target cells by using HIV-1-based lentiviral vectors. To follow the spread of VP22-EGFP to other cells, transduced COS-7 cells were coplated with a number of different cell types, including brain choroid plexus cells, human endothelial cells, H9 cells, and HeLa cells. We found that VP22-EGFP fusion proteins were transported from transduced cells to recipient cells and that such fusion proteins accumulated in the nucleus and in the cytoplasm of such cells. To determine the ability to deliver fusion proteins in vivo, we injected transduced H9 cells as well as the viral vector directly into the brain of mice. We present evidence that VP22-EGFP fusion proteins were transported effectively from lentivirus transduced cells in vivo. We also show that the VP22-EGFP fusion protein encoded by the lentivirus is transported between cells. Our data indicate that such fusion proteins are present in the nucleus and in the cytoplasm of neighboring cells. Therefore, lentiviral vectors may provide a potent biological system for delivering genes encoding therapeutic proteins fused to VP22. PMID:11027330

  11. [Neonatal herpes simplex infection].

    PubMed

    van Ham-Borawitz, Veronique E J; Stam, Edo D; Welborn, Kathleen M; Sas, Theo C J

    2016-01-01

    Neonatal encephalitis caused by herpes simplex virus (HSV) is a familiar disease with a high mortality and morbidity rate. Isolated skin-eye-mouth infection is less familiar among professionals. In this article we present two neonates with an isolated skin lesion caused by an HSV infection. Of the neonates infected with HSV, 40-45% show isolated skin-eye-mouth disease. With correct treatment, the risk of spread to the central nervous system will decrease from 50-60% to 5-10%. Typical HSV skin lesions may present at a late stage of the disease or may be masked by a secondary bacterial infection. When a neonate presents with atypical skin lesions starting 7-12 days after the birth, immediate testing for HSV and immediate treatment are required, to decrease the risk of further progression of the disease.

  12. Herpes Simplex Virus (Cold Sores)

    MedlinePlus

    ... the skin, eyes, and mouth. This is a life-threatening infection that can lead to permanent brain damage or even death. Herpes simplex viruses also cause encephalitis, an infection of the brain. ...

  13. Steatocystoma simplex of the eyelid.

    PubMed

    Procianoy, Fernando; Golbert, Marcelo B; Golbspan, Liane; Duro, Kauê M; Bocaccio, Francisco J L

    2009-01-01

    A 68-year-old woman presented with a nodular pretarsal tumor on her right upper eyelid that had slowly grown over 6 months. Excisional biopsy was performed through an eyelid crease approach, and histopathology evidenced the lesion to be steatocystoma simplex. Steatocystoma simplex is an uncommon benign cutaneous lesion thought to be a circumscribed malformation arising from the pilosebaceous duct junction, rarely reported to occur in the periorbital region.

  14. Viruses and host evolution: virus-mediated self identity.

    PubMed

    Villarreal, Luis

    2012-01-01

    human evolution from the perspective of the great HERV colonization. The origin of a large social brain able to support the learning of language is presented from this viral perspective. The role of addiction modules in the origin of extended social bonding of humans is outlined and applied to the emergence of language as a system of group identity. PMID:22399381

  15. Viruses and host evolution: virus-mediated self identity.

    PubMed

    Villarreal, Luis

    2012-01-01

    human evolution from the perspective of the great HERV colonization. The origin of a large social brain able to support the learning of language is presented from this viral perspective. The role of addiction modules in the origin of extended social bonding of humans is outlined and applied to the emergence of language as a system of group identity.

  16. Lichen simplex chronicus on the ankle (image)

    MedlinePlus

    Lichen simplex chronicus on the ankle: Lichen simplex chronicus is also known as neurodermatitis. A minor itch may encourage scratching which increases the irritation, leading to more scratching. This ...

  17. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3305...

  18. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3305...

  19. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3305...

  20. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3305...

  1. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3305...

  2. Isolation of the major herpes simplex virus type 1 (HSV-1)-specific glycoprotein by hydroxylapatite chromatography and its use in enzyme-linked immunosorbent assay for titration of human HSV-1-specific antibodies.

    PubMed

    Vestergaard, B F; Grauballe, P C

    1979-12-01

    A 131,000 molecular weight herpes simplex virus type 1 (HSV-1) glycoprotein designated antigen number 6 (Ag-6) was previously shown to possess almost exclusively HSV-1-specific antigenic sites. Fused rocket and crossed immunoelectrophoresis of fractions obtained from hydroxylapatite chromatography of crude HSV-1 antigen (Triton X-100-solubilized, infected tissue culture cells) showed that a subfraction of Ag-6 could be separated from the other HSV antigens. Enzyme-linked immunosorbent assay with the isolated Ag-6 showed that sera from rabbits infected with HSV-1 and HSV-1 human antisera contained antibodies to Ag-6, whereas sera from HSV-2-infected rabbits and sera from patients with primary HSV-2 infections did not react with Ag-6. Enzyme-linked immunosorbent assay of 852 human sera for antibodies to HSV type-common glycoproteins, Ag-6, and HSV 2-specific antigens showed that 139 sera which reacted negatively with HSV type-common glycoproteins also did not react with Ag-6 with HSV-2 specific antigens. The 713 sera reacting positively to HSV type-common antigens either reacted with Ag-6 (328 sera) or with HSV-2-specific antigens (31 sera) or both (354 sera). This means that Ag-6 might be useful in large-scale human serology for the detection of past infection with HSV-1, irrespective of whether or not past infection with HSV-2 has occurred.

  3. Volatile Organic Compound Gamma-Butyrolactone Released upon Herpes Simplex Virus Type -1 Acute Infection Modulated Membrane Potential and Repressed Viral Infection in Human Neuron-Like Cells.

    PubMed

    Rochford, Kevin; Chen, Feng; Waguespack, Yan; Figliozzi, Robert W; Kharel, Madan K; Zhang, Qiaojuan; Martin-Caraballo, Miguel; Hsia, S Victor

    2016-01-01

    Herpes Simplex Virus Type -1 (HSV-1) infections can cause serious complications such as keratitis and encephalitis. The goal of this study was to identify any changes in the concentrations of volatile organic compounds (VOCs) produced during HSV-1 infection of epithelial cells that could potentially be used as an indicator of a response to stress. An additional objective was to study if any VOCs released from acute epithelial infection may influence subsequent neuronal infection to facilitate latency. To investigate these hypotheses, Vero cells were infected with HSV-1 and the emission of VOCs was analyzed using two-dimensional gas chromatograph/mass spectrometry (2D GC/MS). It was observed that the concentrations of gamma-butyrolactone (GBL) in particular changed significantly after a 24-hour infection. Since HSV-1 may establish latency in neurons after the acute infection, GBL was tested to determine if it exerts neuronal regulation of infection. The results indicated that GBL altered the resting membrane potential of differentiated LNCaP cells and promoted a non-permissive state of HSV-1 infection by repressing viral replication. These observations may provide useful clues towards understanding the complex signaling pathways that occur during the HSV-1 primary infection and establishment of viral latency. PMID:27537375

  4. Volatile Organic Compound Gamma-Butyrolactone Released upon Herpes Simplex Virus Type -1 Acute Infection Modulated Membrane Potential and Repressed Viral Infection in Human Neuron-Like Cells

    PubMed Central

    Waguespack, Yan; Figliozzi, Robert W.; Kharel, Madan K.; Zhang, Qiaojuan; Martin-Caraballo, Miguel

    2016-01-01

    Herpes Simplex Virus Type -1 (HSV-1) infections can cause serious complications such as keratitis and encephalitis. The goal of this study was to identify any changes in the concentrations of volatile organic compounds (VOCs) produced during HSV-1 infection of epithelial cells that could potentially be used as an indicator of a response to stress. An additional objective was to study if any VOCs released from acute epithelial infection may influence subsequent neuronal infection to facilitate latency. To investigate these hypotheses, Vero cells were infected with HSV-1 and the emission of VOCs was analyzed using two-dimensional gas chromatograph/mass spectrometry (2D GC/MS). It was observed that the concentrations of gamma-butyrolactone (GBL) in particular changed significantly after a 24-hour infection. Since HSV-1 may establish latency in neurons after the acute infection, GBL was tested to determine if it exerts neuronal regulation of infection. The results indicated that GBL altered the resting membrane potential of differentiated LNCaP cells and promoted a non-permissive state of HSV-1 infection by repressing viral replication. These observations may provide useful clues towards understanding the complex signaling pathways that occur during the HSV-1 primary infection and establishment of viral latency. PMID:27537375

  5. Development of a high-throughput β-Gal-based neutralization assay for quantitation of herpes simplex virus-neutralizing antibodies in human samples.

    PubMed

    Baccari, Amy; Cooney, Michael; Blevins, Tamara P; Morrison, Lynda A; Larson, Shane; Skoberne, Mojca; Belshe, Robert B; Flechtner, Jessica B; Long, Deborah

    2016-07-19

    Measurement of neutralizing antibodies against herpes simplex virus (HSV) is important for evaluation of candidate vaccines. The established plaque-reduction neutralization assay is time consuming, labor intensive, and difficult to validate and transfer. Here, we describe the characterization of a HSV-neutralization assay based on the expression of a reporter gene, β-galactosidase (β-Gal). Using previously constructed HSV-β-Gal recombinant viruses, HSV-2/Gal and HSV-1/tk12, we developed a colorimetric β-Gal-based neutralization assay that is sensitive and highly reproducible, and performed in less than 48h. HSV-1 and HSV-2 neutralizing titers measured by the β-Gal-based neutralization assay were equivalent to those obtained by a plaque reduction neutralization assay. Intra- and inter-assay precision studies demonstrated that the β-Gal-based assay was repeatable and yielded low and acceptable variation. In addition, comparison of HSV-2 neutralizing antibody (NAb) titers measured in two independent laboratories by two unique β-Gal-based assays showed a highly significant correlation (r=0.9499, p<0.0001) between the two assays. The new assay will serve as an important tool both for preclinical and clinical trials of new HSV vaccines.

  6. The Significance of Herpes Simplex for School Nurses

    ERIC Educational Resources Information Center

    Ensor, Deirdre

    2005-01-01

    Herpes simplex is a common recurrent viral infection caused by the herpes simplex virus. The two closely related but distinct viruses that cause herpes simplex infections are herpes simplex 1 (HSV-1) and herpes simplex 2 (HSV-2). HSV-1 is commonly associated with infections around the oral mucosa and is the cause of herpes labialis, often referred…

  7. Anisakis simplex allergy: a murine model of anaphylaxis induced by parasitic proteins displays a mixed Th1/Th2 pattern

    PubMed Central

    Baeza, M L; Conejero, L; Higaki, Y; Martín, E; Pérez, C; Infante, S; Rubio, M; Zubeldia, J M

    2005-01-01

    The study of the singular hypersensitivity reactions to Anisakis simplex (A.s) proteins, may help us to undestand many of the unknown immune interactions between helmiths infections and allergy. We have developed a murine model of allergy to A. simplex, that mimics human A. simplex allergy to study the specific aspects of anaphylaxis induced by parasites. Male C3H/HeJ mice were intraperitoneally sensitized to A. simplex. Mice were then intravenous or orally challenged with A. simplex. Antigen-specific immunoglobulins, polyclonal IgE, anaphylactic symptoms, plasma histamine levels and cytokine profiles were determined. Comparative IgE immunoblot analyses were also performed. Specific IgE, IgG1 and IgG2a were detected in sensitized mice since week 3. Polyclonal IgE raised and peaked with different kinetics. Intravenous A. simplex challenge produced anaphylaxis in mice, accompanied by plasma histamine release. Oral A. simplex challenge in similarly sensitized mice did not caused symptoms nor histamine release. Numerous A. simplex allergens were recognized by sensitized mouse sera, some of them similar to human serum. The A. simplex stimulated splenocytes released IL-10, IFN-γ, IL-4, IL-13 and IL-5. We describe a new animal model of anaphylaxis. It exhibits characteristics of type I hypersensitivity reactions to Anisakis simplex similar to those observed in allergic humans. Different responses to i.v. or oral A. simplex challenges emerged, which did not reflect a window tolerization period. The cytokine profile developed (mixed Th1/Th2 pattern) differed from the observed in classical models of anaphylaxis or allergy to food antigens. This model may permit to investigate the peculiar allergic reactions to parasitic proteins. PMID:16297154

  8. Herpes Simplex Virus (HSV) in Infants and Babies

    MedlinePlus

    ... rashes clinical tools newsletter | contact Share | Herpes Simplex Virus (HSV) A parent's guide for infants and babies ... Herpes infections are caused by both herpes simplex virus type 1 (HSV-1) and herpes simplex virus ...

  9. Natural remedies for Herpes simplex.

    PubMed

    Gaby, Alan R

    2006-06-01

    Herpes simplex is a common viral infection of the skin or mucous membranes. The lesions caused by this infection are often painful, burning, or pruritic, and tend to recur in most patients. Short-term treatment with acyclovir can accelerate the healing of an acute outbreak, and continuous acyclovir therapy is often prescribed for people with frequent recurrences. While this drug can reduce the recurrence rate by 60-90 percent, it can also cause a wide array of side effects, including renal failure, hepatitis, and anaphylaxis. Safe and effective alternatives are therefore needed. There is evidence that certain dietary modifications and natural substances may be useful for treating active Herpes simplex lesions or preventing recurrences. Treatments discussed include lysine, vitamin C, zinc, vitamin E, adenosine monophosphate, and lemon balm (Melissa officinalis).

  10. Infection with an H2 recombinant herpes simplex virus vector results in expression of MHC class I antigens on the surfaces of human neuroblastoma cells in vitro and mouse sensory neurons in vivo.

    PubMed

    Abendroth, A; Simmons, A; Efstathiou, S; Pereira, R A

    2000-10-01

    The majority of neurons in herpes simplex virus (HSV)-infected murine sensory ganglia are transiently induced to express MHC-I antigens at the cell surface, whereas only a minority are themselves productively infected. The aim of the current work was to determine whether MHC-I antigens can be expressed on the surfaces of infected neurons in addition to their uninfected neighbours. To address this aim a recombinant HSV type 1 strain, S-130, was used to deliver a mouse H2K(d) gene, under control of the HCMV IE-1 promoter/enhancer, into human neuroblastoma cells in vitro and mouse primary sensory neurons in vivo. S-130 expressed H2K(d) antigens on the surfaces of IMR-32 cells, a human neuroblastoma cell line that expresses very low levels of MHC-I constitutively. In K562 cells, which do not express MHC-I constitutively, H2K(d) and beta(2)-microglobulin (beta(2)m) were shown to be co-expressed at the cell surface following S-130 infection. This observation was taken as evidence that class I heavy chain (alphaC) molecules encoded by the expression cassette in the HSV genome were transported to the cell surface as stable complexes with beta(2)m. Significantly, after introduction of S-130 into flank skin, H2K(d) antigens were detected on the surfaces of primary sensory neurons in ganglia innervating the inoculation site. Our data show that HSV-infected murine primary sensory neurons and human neuroblastoma cells are capable of expressing cell-surface MHC-I molecules encoded by a transgene. From this, we infer that up-regulation of alphaC expression is, in principle, sufficient to overcome potential impediments to neuronal cell surface expression of MHC-I complexes.

  11. Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D.

    PubMed

    Diniz, M O; Ferreira, L C S

    2011-05-01

    Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5) expressing three proteins (E7, E6, and E5) of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id) route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose) induced a strong activation of E7-specific interferon-γ (INF-γ)-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.

  12. Advancing Paternal Age and Simplex Autism

    ERIC Educational Resources Information Center

    Puleo, Connor Morrow; Schmeidler, James; Reichenberg, Abraham; Kolevzon, Alexander; Soorya, Latha V.; Buxbaum, Joseph D.; Silverman, Jeremy M.

    2012-01-01

    De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers' offspring. This study examined whether advancing paternal age predicts an increase in simplex (n = 90) versus multiplex ASD cases (n = 587) in 677 participants (340 families). Whether or not controlling…

  13. Selective in vitro replication of herpes simplex virus type 1 (HSV-1) ICP34.5 null mutants in primary human CNS tumours--evaluation of a potentially effective clinical therapy.

    PubMed Central

    McKie, E. A.; MacLean, A. R.; Lewis, A. D.; Cruickshank, G.; Rampling, R.; Barnett, S. C.; Kennedy, P. G.; Brown, S. M.

    1996-01-01

    Primary tumours of the central nervous system (CNS) are an important cause of cancer-related deaths in adults and children. CNS tumours are mostly glial cell in origin and are predominantly astrocytomas. Conventional therapy of high-grade gliomas includes maximal resection followed by radiation treatment. The addition of adjuvant chemotherapy provides little improvement in survival time and hence assessment of novel therapies is imperative. We have evaluated the potential therapeutic use of the herpes simplex virus (HSV) mutant 1716 in the treatment of primary brain tumours. The mutant is deleted in the RL1 gene and fails to produce the virulence factor ICP34.5. 1716 replication was analysed in both established human glioma cell lines and in primary cell cultures derived from human tumour biopsy material. In the majority of cultures, virus replication occurred and consequential cell death resulted. In the minority of tumour cell lines which are non-permissive for mutant replication, premature shut-off of host cell protein synthesis was induced in response to lack of expression of ICP34.5. Hence RL1-negative mutants have the distinct advantage of providing a double hit phenomenon whereby cell death could occur by either pathway. Moreover, 1716, by virtue of its ability to replicate selectively within a tumour cell, has the potential to deliver a 'suicide' gene product to the required site immediately. It is our opinion that HSV which fails to express ICP34.5 could provide an effective tumour therapy. Images Figure 4 Figure 5 PMID:8795577

  14. Low Prevalence of Varicella Zoster Virus and Herpes Simplex Virus Type 2 in Saliva from Human Immunodeficiency Virus-Infected Persons in the Era of Highly Active Antiretroviral Therapy

    PubMed Central

    Wang, Chunmei C.; Yepes, Luis C.; Danaher, Robert J.; Berger, Joseph R.; Mootoor, Yunanan; Kryscio, Richard J.; Miller, Craig S.

    2009-01-01

    Objectives Human herpesviruses (HHVs), e.g. herpes simplex virus (HSV) type 1, Epstein-Barr virus and cytomegalovirus, appear in saliva at greater frequency in persons infected with human immunodeficiency virus (HIV) than healthy individuals. However, it is not known if varicella zoster virus (VZV) and HSV-2 appear simultaneously during HIV infection at greater frequency in saliva during this era of highly active antiretroviral therapy (HAART). The aim of this study was to investigate the prevalence and amounts of VZV and HSV-2 in the saliva of HIV-infected, orally asymptomatic patients. Study Design Quantitative polymerase chain reaction was used to investigate the prevalence, quantity, risk, and correlates of salivary VZV and HSV-2 from 59 HIV-seropositive individuals and 53 healthy controls in a case-control, cross-sectional study. Seventy-eight percent of the HIV-seropositive patients (46/59) were taking HAART. Results VZV DNA was detected in the saliva of 5.1% (3/59) of the HIV-positive group and in only one healthy control 1.9% (1/53; P = 0.62). The amount of VZV DNA in the expressors was low, generally less than 1,100 copies/mL with no observed difference between the HIV-positive group and the controls (P= 1.0). HSV-2 DNA was not detected in either group. In the HIV-infected group, VZV shedding occurred in those on HAART, but was not associated with oral lesions, specific CD4+ or CD8+ T-cell levels, or demographic factors. Conclusions VZV was detected at low prevalence in the saliva of HIV-infected persons whereas HSV-2 was not detected in the saliva of this cohort. HAART does not appear to diminish the risk for asymptomatic VZV shedding. PMID:20123407

  15. Neonatal Herpes Simplex Virus Infection.

    PubMed

    James, Scott H; Kimberlin, David W

    2015-09-01

    Herpes simplex virus (HSV) 1 and HSV-2 infections are highly prevalent worldwide and are characterized by establishing lifelong infection with periods of latency interspersed with periodic episodes of reactivation. Acquisition of HSV by an infant during the peripartum or postpartum period results in neonatal HSV disease, a rare but significant infection that can be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to improvements in mortality and, to a lesser extent, neurodevelopmental outcomes, but room exists for further improvement.

  16. [Update on Herpes Simplex Encephalitis].

    PubMed

    Kuroda, Hiroshi

    2015-07-01

    Herpes simplex encephalitis (HSE), which is caused by the herpes simplex virus (HSV), is a severe neuro-infectious disease characterized by high mortality and morbidity. We reviewed the pathomechanism, diagnosis, and treatment of HSE based on recent progress in the field. The highlighted mechanism of HSE in this review is immune-mediated tissue damage caused by host immunity. Major symptoms of HSE include psychiatric alteration, Klüver-Bucy syndrome, and amnesia, caused by frequent involvement of the limbic system. An important differential diagnosis of HSE is autoimmune limbic encephalitis, including anti-N-methyl-D-aspartate receptor encephalitis, and anti-voltage-gated K+ channel encephalitis. HSE is definitely diagnosed based on the detection of HSV-DNA by polymerase chain reaction and/or the detection of HSV-IgG antibody in the cerebrospinal fluid (CSF). Repeated CSF examinations are required for the accurate diagnosis of HSE. Acyclovir (ACV) plays a central role in the treatment of HSE, and its early initiation is essential for good outcome in patients with HSE. Acute administration of corticosteroids for HSE is controversial; a randomized, double-blind, placebo-controlled trial to investigate the efficacy of add-on corticosteroids to ACV is ongoing.

  17. [Update on Herpes Simplex Encephalitis].

    PubMed

    Kuroda, Hiroshi

    2015-07-01

    Herpes simplex encephalitis (HSE), which is caused by the herpes simplex virus (HSV), is a severe neuro-infectious disease characterized by high mortality and morbidity. We reviewed the pathomechanism, diagnosis, and treatment of HSE based on recent progress in the field. The highlighted mechanism of HSE in this review is immune-mediated tissue damage caused by host immunity. Major symptoms of HSE include psychiatric alteration, Klüver-Bucy syndrome, and amnesia, caused by frequent involvement of the limbic system. An important differential diagnosis of HSE is autoimmune limbic encephalitis, including anti-N-methyl-D-aspartate receptor encephalitis, and anti-voltage-gated K+ channel encephalitis. HSE is definitely diagnosed based on the detection of HSV-DNA by polymerase chain reaction and/or the detection of HSV-IgG antibody in the cerebrospinal fluid (CSF). Repeated CSF examinations are required for the accurate diagnosis of HSE. Acyclovir (ACV) plays a central role in the treatment of HSE, and its early initiation is essential for good outcome in patients with HSE. Acute administration of corticosteroids for HSE is controversial; a randomized, double-blind, placebo-controlled trial to investigate the efficacy of add-on corticosteroids to ACV is ongoing. PMID:26160820

  18. A Herpes Simplex Virus Type 1 Human Asymptomatic CD8+ T-Cell Epitopes-Based Vaccine Protects Against Ocular Herpes in a “Humanized” HLA Transgenic Rabbit Model

    PubMed Central

    Srivastava, Ruchi; Khan, Arif A.; Huang, Jiawei; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

    2015-01-01

    Purpose. A clinical vaccine that protects from ocular herpes simplex virus type 1 (HSV-1) infection and disease still is lacking. In the present study, preclinical vaccine trials of nine asymptomatic (ASYMP) peptides, selected from HSV-1 glycoproteins B (gB), and tegument proteins VP11/12 and VP13/14, were performed in the “humanized” HLA–transgenic rabbit (HLA-Tg rabbit) model of ocular herpes. We recently reported that these peptides are highly recognized by CD8+ T cells from “naturally” protected HSV-1–seropositive healthy ASYMP individuals (who have never had clinical herpes disease). Methods. Mixtures of three ASYMP CD8+ T-cell peptides derived from either HSV-1 gB, VP11/12, or VP13/14 were delivered subcutaneously to different groups of HLA-Tg rabbits (n = 10) in incomplete Freund's adjuvant, twice at 15-day intervals. The frequency and function of HSV-1 epitope-specific CD8+ T cells induced by these peptides and their protective efficacy, in terms of survival, virus replication in the eye, and ocular herpetic disease were assessed after an ocular challenge with HSV-1 (strain McKrae). Results. All mixtures elicited strong and polyfunctional IFN-γ– and TNF-α–producing CD107+CD8+ cytotoxic T cells, associated with a significant reduction in death, ocular herpes infection, and disease (P < 0.015). Conclusions. The results of this preclinical trial support the screening strategy used to select the HSV-1 ASYMP CD8+ T-cell epitopes, emphasize their valuable immunogenic and protective efficacy against ocular herpes, and provide a prototype vaccine formulation that may be highly efficacious for preventing ocular herpes in humans. PMID:26098469

  19. Addition of a C-Terminal Cysteine Improves the Anti-Herpes Simplex Virus Activity of a Peptide Containing the Human Immunodeficiency Virus Type 1 TAT Protein Transduction Domain▿

    PubMed Central

    Bultmann, Hermann; Teuton, Jeremy; Brandt, Curtis R.

    2007-01-01

    Previous studies have shown that peptides containing the protein transduction domain (PTD) of the human immunodeficiency virus tat protein (GRKKRRQRRR) were effective inhibitors of herpes simplex virus type 1 (HSV-1) entry (H. Bultmann and C. R. Brandt, J. Biol. Chem. 277:36018-36023, 2002). We now show that the addition of a single cysteine residue to the C terminus of the TAT PTD (TAT-C peptide) improves the antiviral activity against HSV-1 and HSV-2. The principle effect of adding the cysteine was to enable the peptide to inactivate virions and to induce a state of resistance to infection in cells pretreated with peptide. The TAT-C peptide acted extracellularly, immediately blocked entry of adsorbed virus, prevented VP16 translocation to the nucleus, and blocked syncytium formation and cell-cell spread. Thus, TAT-C peptides are fusion inhibitors. The induction of the resistance of cells to infection was rapid, recovered with a half-life of 5 to 6 h, and could be reinduced by peptide treatment. TAT-C bound to heparan sulfate but was a poor competitor for viral attachment. The antiviral activity depended on the net positive charge of the peptide but not on chirality, and a free sulfhydryl group was not essential for antiviral activity because TAT-C dimers were at least as effective as monomers. The unique combination of antiviral activities and low toxicity combine to make TAT-C a strong candidate for further development as a drug to block HSV infection. PMID:17261627

  20. Herpes Simplex (Cold Sores and Genital Herpes)

    MedlinePlus

    ... Select a Language: Fact Sheet 508 Herpes Simplex (Cold Sores and Genital Herpes) WHAT IS HERPES? HSV ... virus 1 (HSV1) is the common cause of cold sores (oral herpes) around the mouth. HSV2 normally ...

  1. Structural Characterization of Interaction between Human Ubiquitin-specific Protease 7 and Immediate-Early Protein ICP0 of Herpes Simplex Virus-1*

    PubMed Central

    Pozhidaeva, Alexandra K.; Mohni, Kareem N.; Dhe-Paganon, Sirano; Arrowsmith, Cheryl H.; Weller, Sandra K.; Korzhnev, Dmitry M.; Bezsonova, Irina

    2015-01-01

    Human ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that prevents protein degradation by removing polyubiquitin chains from its substrates. It regulates the stability of a number of human transcription factors and tumor suppressors and plays a critical role in the development of several types of cancer, including prostate and small cell lung cancer. In addition, human USP7 is targeted by several viruses of the Herpesviridae family and is required for effective herpesvirus infection. The USP7 C-terminal region (C-USP7) contains five ubiquitin-like domains (UBL1–5) that interact with several USP7 substrates. Although structures of the USP7 C terminus bound to its substrates could provide vital information for understanding USP7 substrate specificity, no such data has been available to date. In this work we have demonstrated that the USP7 ubiquitin-like domains can be studied in isolation by solution NMR spectroscopy, and we have determined the structure of the UBL1 domain. Furthermore, we have employed NMR and viral plaque assays to probe the interaction between the C-USP7 and HSV-1 immediate-early protein ICP0 (infected cell protein 0), which is essential for efficient lytic infection and virus reactivation from latency. We have shown that depletion of the USP7 in HFF-1 cells negatively affects the efficiency of HSV-1 lytic infection. We have also found that USP7 directly binds ICP0 via its C-terminal UBL1–2 domains and mapped the USP7-binding site for ICP0. Therefore, this study represents a first step toward understanding the molecular mechanism of C-USP7 specificity toward its substrates and may provide the basis for future development of novel antiviral and anticancer therapies. PMID:26224631

  2. Synthesis of heparan and chondroitin sulfate proteoglycans by human endothelial cells is differentially affected by herpes simplex virus type I (HSV-1)

    SciTech Connect

    Kaner, R.J.; Iozzo, R.V.; Ziaie, Z.; Kefalides, N.A.

    1987-05-01

    Effects of HSV-1 infection on proteoglycan (PG) synthesis by human EC were studied as a model of EC injury. Confluent cultures of early passage umbilical vein EC were infected with HSV-1 at multiplicities of infection (MOI) from 0.001 to 1.0. In uninfected cultures, over 90% of the total (/sup 35/S)sulfate-labeled macromolecules were divided into two major peaks on ion-exchange chromatography. One contained heparan sulfate (HSPG) and the other chondroitin/dermatan sulfate (CS/DSPG) proteoglycan. HSV-1 infection produced a dose-dependent inhibition of total PG synthesis of up to 75%. There were widely divergent effects on individual PG species. Inhibition of CS/DSPG synthesis was much more marked than that of the HSPG. At a MOI of 1.0, CS/DSPG was present at 13% of control values, compared to 30% for HSPG. There was about one log difference in the dose of virus required to produce 50% inhibition of cell/matrix HSPG relative to CS/DSPG. HSV-1 did not inhibit the generation of an undersulfated HSPG, which contained shorter glycosaminoglycan chains than the predominant species. The authors conclude that HSV-1 infection of human EC produces complex differential effects on proteoglycan synthesis.

  3. Herpes simplex-like infection in a bottlenose dolphin stranded in the Canary Islands.

    PubMed

    Esperón, F; Fernández, A; Sánchez-Vizcaíno, J M

    2008-08-19

    A bottlenose dolphin, stranded in the Canary Islands in 2001 exhibited non-suppurative encephalitis. No molecular detection of cetacean morbillivirus (CeMV) was found, but a herpesviral-specific band of 250 bp was detected in the lung and brain. The sequenced herpesviral PCR product was compared with GenBank sequences, obtaining 98% homology (p-distance of 0.02) with Human herpesvirus 1 (herpes simplex virus 1 or HSV-1). This is the first report of a herpes simplex-like infection in a stranded dolphin. PMID:18828564

  4. Antihelmintic effects of nutmeg (Myristica fragans) on Anisakis simplex L3 larvae obtained from Micromesistius potassou.

    PubMed

    López, Víctor; Gerique, Javier; Langa, Elisa; Berzosa, César; Valero, Marta Sofía; Gómez-Rincón, Carlota

    2015-06-01

    Anisakis simplex is a foodborne pathogen that can produce human infections and allergic reactions due to the high consumption of raw fish. The seeds of Myristica fragans (Myristicaceae), popularly known as nutmeg, are worldwide used as a culinary spice due to its flavour and properties in food preservation. A nutmeg extract was prepared, analyzed, screened for cytotoxicity and tested against Anisakis simplex L3 larvae. In order to detect the biologically active constituents of the extract, myristicin was tested on the larvae. An acetylcholinesterase inhibition bioassay was also carried out to investigate the antihelmintic mechanism of action. Our results demonstrate that nutmeg exerts antihelmintic effects on Anisakis simplex, being myristicin one of the active compounds. The extract induced a high rate of dead anisakis at concentrations between 0.5 and 0.7 mg/ml without being considered cytotoxic; however, an inhibition of acetylcholinesterase was discarded as the molecular mechanism involved in the activity.

  5. Antihelmintic effects of nutmeg (Myristica fragans) on Anisakis simplex L3 larvae obtained from Micromesistius potassou.

    PubMed

    López, Víctor; Gerique, Javier; Langa, Elisa; Berzosa, César; Valero, Marta Sofía; Gómez-Rincón, Carlota

    2015-06-01

    Anisakis simplex is a foodborne pathogen that can produce human infections and allergic reactions due to the high consumption of raw fish. The seeds of Myristica fragans (Myristicaceae), popularly known as nutmeg, are worldwide used as a culinary spice due to its flavour and properties in food preservation. A nutmeg extract was prepared, analyzed, screened for cytotoxicity and tested against Anisakis simplex L3 larvae. In order to detect the biologically active constituents of the extract, myristicin was tested on the larvae. An acetylcholinesterase inhibition bioassay was also carried out to investigate the antihelmintic mechanism of action. Our results demonstrate that nutmeg exerts antihelmintic effects on Anisakis simplex, being myristicin one of the active compounds. The extract induced a high rate of dead anisakis at concentrations between 0.5 and 0.7 mg/ml without being considered cytotoxic; however, an inhibition of acetylcholinesterase was discarded as the molecular mechanism involved in the activity. PMID:25890576

  6. Zebrafish: modeling for herpes simplex virus infections.

    PubMed

    Antoine, Thessicar Evadney; Jones, Kevin S; Dale, Rodney M; Shukla, Deepak; Tiwari, Vaibhav

    2014-02-01

    For many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds. In addition, the presence of human homologs of viral entry receptors in zebrafish such as 3-O sulfated heparan sulfate, nectins, and tumor necrosis factor receptor superfamily member 14-like receptor bring strong rationale for virologists to test their in vivo significance in viral entry in a zebrafish model and compare the structure-function basis of virus zebrafish receptor interaction for viral entry. On the other end, a zebrafish model is already being used for studying inflammation and angiogenesis, with or without genetic manipulations, and therefore can be exploited to study viral infection-associated pathologies. The major advantage with zebrafish is low cost, easy breeding and maintenance, rapid lifecycle, and a transparent nature, which allows visualizing dissemination of fluorescently labeled virus infection in real time either at a localized region or the whole body. Further, the availability of multiple transgenic lines that express fluorescently tagged immune cells for in vivo imaging of virus infected animals is extremely attractive. In addition, a fully developed immune system and potential for receptor-specific knockouts further advocate the use of zebrafish as a new tool to study viral infections. In this review, we focus on expanding the potential of zebrafish model system in understanding human infectious diseases and future benefits.

  7. Topical Herpes Simplex Virus 2 (HSV-2) Vaccination with Human Papillomavirus Vectors Expressing gB/gD Ectodomains Induces Genital-Tissue-Resident Memory CD8+ T Cells and Reduces Genital Disease and Viral Shedding after HSV-2 Challenge

    PubMed Central

    Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N.; Pang, Yuk Ying; Thompson, Cynthia D.; Lowy, Douglas R.; Cohen, Jeffrey I.

    2014-01-01

    ABSTRACT No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8+ T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8+ T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. IMPORTANCE Genital herpes is a highly prevalent chronic

  8. Identification of autoclave-resistant Anisakis simplex allergens.

    PubMed

    Carballeda-Sangiao, Noelia; Olivares, Fabiola; Rodriguez-Mahillo, Ana I; Careche, Mercedes; Tejada, Margarita; Moneo, Ignacio; González-Muñoz, Miguel

    2014-04-01

    Anisakis simplex is a fish parasite able to induce allergic reactions in humans infected when eating raw or undercooked fish parasitized with viable third-stage larvae. Some authors claim that exposure to nonviable Anisakis material can result in allergic symptoms in previously sensitized patients, indicating that parasite allergens are resistant to the thermal treatments of usual cooking procedures. Furthermore, some patients report symptoms after eating canned fish. The aim of this work was the analysis of parasite allergen stability in heating to 121 °C in an autoclave to simulate the thermal process applied to canned fish. Third-stage larvae were subjected to autoclaving for 20, 40, and 80 min, and parasite crude extracts were analyzed by electrophoresis, immunoblotting, and a flow-cytometric basophil activation test. Allergens resistant to autoclaving were separated by reversed-phase high-performance liquid chromatography and identified by ion trap mass spectrometry. Protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that autoclaving considerably reduced the number and intensity of identifiable protein bands in a time-dependent manner. Several allergens were detected by immunoblotting with a pool of A. simplex allergic patients' sera after autoclaving. Allergens of 9 and 14 kDa resistant to autoclaving were identified as Ani s 4 and Ani s 1 allergens, respectively. Functional analysis showed that allergens retain their capacity to activate basophils even after autoclaving for 80 min. In conclusion, some relevant A. simplex allergens retain their capacity to bind immunoglobulin E and activate basophils after being subjected to autoclaving, which is a method equivalent to that used in industrial canning processes. PMID:24680072

  9. Herpes Simplex Encephalitis: An Uncommon Presentation

    PubMed Central

    Bansal, Sunil; Bhatia, Rohan; Ahmad, Sohaib

    2016-01-01

    Herpes Simplex Virus (HSV) encephalitis is an uncommon illness, with about 2 cases per 250,000 per year. Most are caused by HSV-1, with 10% having HSV-2 as the aetiologic factor. We present a case of Herpes simplex type1encephalitis in a 70 year old male with an uncommon presentation. The patient was a known case of endogenous depression with no medical records and on no treatment for the same, reported with acute changes in mental state for the past five days. He was talking irrelevantly, had hallucinations and was unduly aggressive and violent. He was subjected to a thorough clinical and diagnostic work-up which included cerebrospinal fluid analysis, CT head and MRI brain. MRI brain was suggestive of mild subdural effusion which hinted towards infectious cause of encephalitis. The cerebrospinal fluid viral serology panel detected herpes simplex type 1 virus (HSV1) that was later confirmed by CSF Polymerase Chain Reaction (PCR) technique. Hence, acyclovir was initiated by intravenous route at a dosage of 10mg/kg body weight and continued for two weeks. This case holds significance in view of the fact that organic causes must be excluded in suspected cases of psychiatric illness especially in the absence of fever. Also, CSF-PCR testing plays a pivotal role in diagnosing herpes simplex encephalitis. PMID:27437286

  10. Herpes Simplex Encephalitis: An Uncommon Presentation.

    PubMed

    Kaeley, Nidhi; Bansal, Sunil; Bhatia, Rohan; Ahmad, Sohaib

    2016-05-01

    Herpes Simplex Virus (HSV) encephalitis is an uncommon illness, with about 2 cases per 250,000 per year. Most are caused by HSV-1, with 10% having HSV-2 as the aetiologic factor. We present a case of Herpes simplex type1encephalitis in a 70 year old male with an uncommon presentation. The patient was a known case of endogenous depression with no medical records and on no treatment for the same, reported with acute changes in mental state for the past five days. He was talking irrelevantly, had hallucinations and was unduly aggressive and violent. He was subjected to a thorough clinical and diagnostic work-up which included cerebrospinal fluid analysis, CT head and MRI brain. MRI brain was suggestive of mild subdural effusion which hinted towards infectious cause of encephalitis. The cerebrospinal fluid viral serology panel detected herpes simplex type 1 virus (HSV1) that was later confirmed by CSF Polymerase Chain Reaction (PCR) technique. Hence, acyclovir was initiated by intravenous route at a dosage of 10mg/kg body weight and continued for two weeks. This case holds significance in view of the fact that organic causes must be excluded in suspected cases of psychiatric illness especially in the absence of fever. Also, CSF-PCR testing plays a pivotal role in diagnosing herpes simplex encephalitis. PMID:27437286

  11. Can Herpes Simplex Virus Encephalitis Cause Aphasia?

    ERIC Educational Resources Information Center

    Naude, H.; Pretorius, E.

    2003-01-01

    Aphasia implies the loss or impairment of language caused by brain damage. The key to understanding the nature of aphasic symptoms is the neuro-anatomical site of brain damage, and not the causative agent. However, because "Herpes simplex" virus (HSV) encephalitis infection usually affects the frontal and temporal lobes, subcortical structures and…

  12. Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

    PubMed Central

    Audicana, M. Teresa; Kennedy, Malcolm W.

    2008-01-01

    Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive. PMID:18400801

  13. Molecular Cloning and Expression of a New Major Allergen, Ani s 14, from Anisakis simplex.

    PubMed

    Kobayashi, Yukihiro; Kakemoto, Seiko; Shimakura, Kuniyoshi; Shiomi, Kazuo

    2015-01-01

    The nematode Anisakis simplex is a representative parasite infecting marine animals. When third stage larvae of A. simplex infecting fish and squids are ingested by humans, individuals previously sensitized by this parasite may experience IgE-mediated allergic reactions. So far, as many as 13 kinds of proteins (Ani s 1-13) have been identified as A. simplex allergens but several more unknown allergens are suggested to exist. In this study, therefore, chemiluminescent immunoscreening of an expression cDNA library constructed from the third stage larvae was conducted to identify a new allergen. As a result, an IgE-positive clone coding for a 23.5 kDa protein (named Ani s 14) composed of 217 amino acid residues was isolated. The regions 4-147 and 34-123 of Ani s 14 share 31% identity with the region 796-940 of Ani s 7 and 32% identity with the region 2-91 of Ani s 12, respectively. Recombinant Ani s 14 was successfully expressed in Escherichia coli as a His-tagged protein and shown to be IgE reactive to 14 (54%) of 26 sera from Anisakis-allergic patients. In conclusion, Ani s 14 is a new major allergen of A. simplex that is specific to Anisakis-allergic patients.

  14. Pediatric cancer gone viral. Part II: potential clinical application of oncolytic herpes simplex virus-1 in children

    PubMed Central

    Friedman, Gregory K; Beierle, Elizabeth A; Gillespie, George Yancey; Markert, James M; Waters, Alicia M; Chen, Chun-Yu; Denton, Nicholas L; Haworth, Kellie B; Hutzen, Brian; Leddon, Jennifer L; Streby, Keri A; Wang, Pin-Yi; Cripe, Timothy P

    2015-01-01

    Oncolytic engineered herpes simplex viruses (HSVs) possess many biologic and functional attributes that support their use in clinical trials in children with solid tumors. Tumor cells, in an effort to escape regulatory mechanisms that would impair their growth and progression, have removed many mechanisms that would have protected them from virus infection and eventual virus-mediated destruction. Viruses engineered to exploit this weakness, like mutant HSV, can be safely employed as tumor cell killers, since normal cells retain these antiviral strategies. Many preclinical studies and early phase trials in adults demonstrated that oncolytic HSV can be safely used and are highly effective in killing tumor cells that comprise pediatric malignancies, without generating the toxic side effects of nondiscriminatory chemotherapy or radiation therapy. A variety of engineered viruses have been developed and tested in numerous preclinical models of pediatric cancers and initial trials in patients are underway. In Part II of this review series, we examine the preclinical evidence to support the further advancement of oncolytic HSV in the pediatric population. We discuss clinical advances made to date in this emerging era of oncolytic virotherapy. PMID:26436134

  15. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis

    PubMed Central

    Atanur, Santosh; Musilová, Alena; Zídek, Václav; Saba, Laura; Warnecke, Andreas; Khademi, Mohsen; Studahl, Marie; Aurelius, Elisabeth; Hjalmarsson, Anders; Garcia-Diaz, Ana; Denis, Cécile V.; Bergström, Tomas; Sköldenberg, Birgit; Kockum, Ingrid; Aitman, Timothy; Hübner, Norbert; Olsson, Tomas; Pravenec, Michal; Diez, Margarita

    2016-01-01

    Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines—generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89–174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11–2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE. PMID:27224245

  16. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    PubMed

    Abdelmagid, Nada; Bereczky-Veress, Biborka; Atanur, Santosh; Musilová, Alena; Zídek, Václav; Saba, Laura; Warnecke, Andreas; Khademi, Mohsen; Studahl, Marie; Aurelius, Elisabeth; Hjalmarsson, Anders; Garcia-Diaz, Ana; Denis, Cécile V; Bergström, Tomas; Sköldenberg, Birgit; Kockum, Ingrid; Aitman, Timothy; Hübner, Norbert; Olsson, Tomas; Pravenec, Michal; Diez, Margarita

    2016-01-01

    Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  17. Herpes Simplex Encephalitis: Two Fatal Cases

    PubMed Central

    Hader, W.; Bayatpour, M.; Dempster, G.; Rozdilsky, B.

    1967-01-01

    The clinical and pathological features of the first two reported cases of herpes simplex encephalitis occurring in Saskatchewan are presented. The clinical history of an acute onset, an early organic mental syndrome followed by coma, neurologic disturbances, rapid progression and death suggests the diagnosis. The acute, diffuse, inflammatory process with predominant involvement of the temporal lobes of the cerebral hemispheres and the presence of intranuclear inclusions in nerve and glial cells are illustrated. The viral particles were found in electron micrographs from the brain tissue of both patients. The definitive diagnosis was established by the isolation, from postmortem brain tissue, of the herpes simplex virus, which was grown in tissue culture and shown to be pathogenic in suckling mice. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 7Fig. 5Fig. 6 PMID:4290725

  18. Simplex method in problems of light-beam phase control.

    PubMed

    Chesnokov, S S; Davletshina, I V

    1995-12-20

    The possibility of the application of the simplex method to problems of wave-front control for light beams propagating in a nonlinear medium is investigated. A numerical analysis of simplex-method effectiveness in comparison with the gradient procedure of hill climbing is carried out. The regimes of stationary and nonstationary wind refraction are considered. The simplest optimization of the simplex size and the control basis is done. PMID:21068958

  19. Valacyclovir for Herpes Simplex Encephalitis ▿

    PubMed Central

    Pouplin, Thomas; Pouplin, Julie Nguyen; Van Toi, Pham; Lindegardh, Niklas; Rogier van Doorn, H.; Hien, Tran Tinh; Farrar, Jeremy; Török, M. Estée; Chau, Tran Thi Hong

    2011-01-01

    The recommended treatment for herpes simplex encephalitis (HSE) remains intravenous acyclovir. In resource-poor countries, however, intravenous formulations are usually unavailable or unaffordable. We report the penetration of acyclovir into the cerebrospinal fluid (CSF) in patients with HSE, treated with the oral prodrug valacyclovir at 1,000 mg three times daily. The oral therapy achieved adequate acyclovir concentrations in the CSF and may be an acceptable early treatment for suspected HSE in resource-limited settings. PMID:21576427

  20. Herpes simplex virus infection during pregnancy.

    PubMed

    Stephenson-Famy, Alyssa; Gardella, Carolyn

    2014-12-01

    Genital herpes in pregnancy continues to cause significant maternal morbidity, with an increasing number of infections being due to oral-labial transmission of herpes simplex virus (HSV)-1. Near delivery, primary infections with HSV-1 or HSV-2 carry the highest risk of neonatal herpes infection, which is a rare but potentially devastating disease for otherwise healthy newborns. Prevention efforts have been limited by lack of an effective intervention for preventing primary infections and the unclear role of routine serologic testing.

  1. [Diagnostic pitfall: herpes simplex recidivans on the finger].

    PubMed

    Weisenseel, Peter; Sander, Erika; Prinz, Jörg

    2003-11-01

    Herpes simplex recidivans is one of the most common dermatological infections. In typical (perioral, labial or genital) localization, the diagnosis is simple and often made by the patient. In atypical locations, the disease may be misdiagnosed by the physician. A 28-year-old patient presented with recurrent herpes simplex virus exacerbations on his left index finger, accompanied by neuralgic pains and lymphadenitis. He had been misdiagnosed by a variety of specialists for several years and had often been unable to work. The diagnosis of recurrent herpes simplex was made by the patient's history and the clinical symptoms and was confirmed by the detection of Herpes simplex virus-specific DNA by PCR.

  2. Photocytotoxic pheophorbide-related compounds from Aglaonema simplex.

    PubMed

    Chee, Chin-Fei; Lee, Hong Boon; Ong, Hean Chooi; Ho, Anthony Siong-Hock

    2005-12-01

    In our screening program for new photosensitizers from the Malaysian biodiversity, we found five pheophorbide-related compounds from the leaves and stems of Aglaonema simplex. Detailed spectroscopic analyses showed that compounds 1-3 and 5 are pheophorbide and hydroxy pheophorbide derivatives of chlorophyll a and b. Compound 4, identified as 15(1)-hydroxypurpurin-7-lactone ethyl methyl diester, was isolated for the first time from the Araceae family. An MTT-based short-term survival assay showed that all five compounds exhibit moderate-to-strong photocytotoxic activities towards human leukemia (HL60) and two oral squamous carcinoma cell lines (HSC-2 and HSC-3). Compounds 4 and 5 showed the strongest photocytotoxicities, with IC(50) values of 0.30-0.41 muM (Table 2). Compounds 1-3 with Et chains at C(17(3)) were less photocytotoxic than the parent pheophorbide a (5).

  3. New strategies against drug resistance to herpes simplex virus.

    PubMed

    Jiang, Yu-Chen; Feng, Hui; Lin, Yu-Chun; Guo, Xiu-Rong

    2016-03-01

    Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV. PMID:27025259

  4. New strategies against drug resistance to herpes simplex virus

    PubMed Central

    Jiang, Yu-Chen; Feng, Hui; Lin, Yu-Chun; Guo, Xiu-Rong

    2016-01-01

    Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV. PMID:27025259

  5. Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus.

    PubMed

    Padma, P; Pramod, N P; Thyagarajan, S P; Khosa, R L

    1998-05-01

    Annona muricata (Annonaceae) and Petunia nyctaginiflora (Solanaceae) were screened for their activity against Herpes simplex virus-1 (HSV-1) and clinical isolate (obtained from the human keratitis lesion). We have looked at the ability of extract(s) to inhibit the cytopathic effect of HSV-1 on vero cells as indicative of anti-HSV-1 potential. The minimum inhibitory concentration of ethanolic extract of A. muricata and aqueous extract of P. nyctaginiflora was found to be 1 mg/ml.

  6. Herpes Simplex Vaccines: Prospects of Live-attenuated HSV Vaccines to Combat Genital and Ocular infections

    PubMed Central

    Stanfield, Brent; Kousoulas, Konstantin Gus

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials. Consensus research findings suggest that robust humoral and cellular immune responses may partially control the frequency of reactivation episodes and reduce clinical symptoms. Live-attenuated viral vaccines have long been considered as a viable option for generating robust and protective immune responses against viral pathogens. Varicella zoster virus (VZV) belongs to the same alphaherpesvirus subfamily with herpes simplex viruses. A live-attenuated VZV vaccine has been extensively used in a prophylactic and therapeutic approach to combat primary and recurrent VZV infection indicating that a similar vaccine approach may be feasible for HSVs. In this review, we summarize pre-clinical approaches to HSV vaccine development and current efforts to test certain vaccine approaches in human clinical trials. Also, we discuss the potential advantages of using a safe, live-attenuated HSV-1 vaccine strain to protect against both HSV-1 and HSV-2 infections. PMID:27114893

  7. Long-term observation of herpes simplex virus type 1 (HSV-1) infection in a child with Wiskott-Aldrich syndrome and a possible reactivation mechanism for thymidine kinase-negative HSV-1 in humans.

    PubMed

    Shiota, Tomoyuki; Kurane, Ichiro; Morikawa, Shigeru; Saijo, Masayuki

    2011-01-01

    Herpes simplex virus type 1 (HSV-1) infections in a child with congenital immunodeficiency syndrome were observed over a 10-year period. The child suffered from recurrent and severe HSV-1 mucocutaneous infections. He frequently suffered from acyclovir (ACV)-resistant (ACV(r)) HSV-1 infection in the later phase of his life, especially after the episode of ACV(r) HSV-1 infection. Virological analyses on the HSV-1 isolates recovered from this patient revealed that all the ACV(r) HSV-1 isolates were thymidine kinase (TK)-negative (TK(-)) due to a single cytosine (C) deletion within the 4-C residues (positions 1061 to 1064) in the TK gene, indicating that the recurrent TK(-)/ACV(r) HSV-1 infections throughout the patient's life were due to the identical ACV(r) HSV-1 strain. Furthermore, it was found that the ACV-sensitive (ACV(s)) isolate recovered from the skin lesions that appeared between the episodes of ACV(r) infection at the ages of 8 and 9 contained ACV(r) HSV-1 with the same mutation in the TK gene. These results indicate that, although TK activity is required for reactivation of TK(+)/ACV(s) HSV-1 from latency and TK(-)/ACV(r) HSV-1 is unable to reactivate from latency, the TK(-)/ACV(r) HSV-1 strain isolated herein reactivated in this patient, possibly by using the TK activity induced by the latently co-infected TK(+)/ACV(s) HSV-1.

  8. Developing protocols for recombinant adeno-associated virus-mediated gene therapy in space.

    PubMed

    Ohi, S

    2000-07-01

    With the advent of the era of International Space Station (ISS) and Mars exploration, it is important more than ever to develop means to cure genetic and acquired diseases, which include cancer and AIDS, for these diseases hamper human activities. Thus, our ultimate goal is to develop protocols for gene therapy, which are suitable to humans on the earth as well as in space. Specifically, we are trying to cure the hemoglobinopathies, beta-thalassemia (Cooley's anemia) and sickle cell anemia, by gene therapy. These well-characterized molecular diseases serve as models for developing ex vivo gene therapy, which would apply to other disorders as well. For example, the procedure may become directly relevant to treating astronauts for space-anemia, immune suppression and bone marrow derived tumors, e.g. leukemia. The adeno-associated virus serotype 2 (AAV2) is a non-pathogenic human parvovirus with broad host-range and tissue specificity. Exploiting these characteristics we have been developing protocols for recombinant AAV2 (rAAV)-based gene therapy. With the rAAV constructs and hematopoietic stem cell (HSC) culture systems in hand, we are currently attempting to cure the mouse model of beta-thalassemia [C57BL/6- Hbbth/Hbbth, Hb(d-minor)] by HSC transplantation (HST) as well as by gene therapy. This paper describes the current status of our rAAV-gene therapy research.

  9. Mixing and Simplex Search for Optimal Illumination in Machine Vision

    NASA Astrophysics Data System (ADS)

    Kim, HyungTae; Cho, KyeongYong; Jin, Kyungchan; Yoon, JooSung; Cho, YoungJune

    2014-07-01

    Mixed-color illumination affects the quality of images in industrial vision system and it is important to optimize color and intensity for image acquisition. This study used simplex search to find the optimal illumination in a short amount of time. A typical color mixer synthesized various color of lights by changing the inputs of RGB power LEDs and passing the lights through an optical system. The image quality under mixed-color illumination was calculated according to the sharpness. For the purpose of optimal illumination using simplex search, a probe network was organized with N + 1probing points for N inputs. The shape of the probe network, simplex, was varied through procedures of extension, contraction, and shrinkage. The inputs of the color mixer were changed until the size of the simplex became smaller than a threshold. The simplex search was tested for commercial semiconductor patterns, and was useful for finding the optimal illumination.

  10. Preventing herpes simplex virus in the newborn.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2014-12-01

    Genital herpes simplex virus (HSV) infections are very common worldwide. Approximately 22% of pregnant women are infected genitally with HSV, and most of them are unaware of this. The most devastating consequence of maternal genital herpes is HSV disease in the newborn. Although neonatal HSV infections remain uncommon, due to the significant morbidity and mortality associated with the infection, HSV infection in the newborn is often considered in the differential diagnosis of ill neonates. This review summarizes the epidemiology and management of neonatal HSV infections and discusses strategies to prevent HSV infection in the newborn.

  11. Translational Data from Adeno-Associated Virus-Mediated Gene Therapy of Hemophilia B in Dogs

    PubMed Central

    Whitford, Margaret H.; Arruda, Valder R.; Stedman, Hansell H.; Kay, Mark A.; High, Katherine A.

    2015-01-01

    Abstract Preclinical testing of new therapeutic strategies in relevant animal models is an essential part of drug development. The choice of animal models of disease that are used in these studies is driven by the strength of the translational data for informing about safety, efficacy, and success or failure of human clinical trials. Hemophilia B is a monogenic, X-linked, inherited bleeding disorder that results from absent or dysfunctional coagulation factor IX (FIX). Regarding preclinical studies of adeno-associated virus (AAV)-mediated gene therapy for hemophilia B, dogs with severe hemophilia B (<1% FIX) provide well-characterized phenotypes and genotypes in which a species-specific transgene can be expressed in a mixed genetic background. Correction of the hemophilic coagulopathy by sustained expression of FIX, reduction of bleeding events, and a comprehensive assessment of the humoral and cell-mediated immune responses to the expressed transgene and recombinant AAV vector are all feasible end points in these dogs. This review compares the preclinical studies of AAV vectors used to treat dogs with hemophilia B with the results obtained in subsequent human clinical trials using muscle- and liver-based approaches. PMID:25675273

  12. Allergenic properties and cuticle microstructure of Anisakis simplex L3 after freezing and pepsin digestion.

    PubMed

    Rodríguez-Mahillo, Ana I; González-Muñoz, Miguel; Moneo, Ignacio; Solas, M Teresa; Mendizábal, Angel; de las Heras, Cristina; Tejada, Margarita

    2008-12-01

    This article examines the viability of and the alterations to the larval cuticle and the pattern of the antigens released when live or frozen Anisakis simplex larvae were treated with acid and pepsin. The results showed that freezing did not greatly alter the larva body. If ruptures were observed, the antigen release to the incubation media was not enhanced, and most of the antigenic content was retained inside the bodies of the larvae. The immunoblotting assay demonstrated that most of the antigens released, including the allergen Ani s 4, were resistant to pepsin. Freezing killed the larvae, but their survival was not compromised by acid treatment or pepsin digestion when kept chilled. All these findings support recommendations about freezing fish for consumption raw or undercooked to prevent human infection by A. simplex larvae. However, our data show that the antigenicity of the larvae is preserved after freezing and may explain why some sensitized patients develop symptoms after ingestion of infested frozen fish.

  13. Early events in herpes simplex virus type 1 infection: photosensitivity of fluorescein isothiocyanate-treated virions

    SciTech Connect

    DeLuca, N.; Bzik, D.; Person, S.; Snipes, W.

    1981-02-01

    Herpes simplex virus type 1 is photosensitized by treatment with fluorescein isothiocyanate (FITC). The inactivation of FITC-treated virions upon subsequent exposure to light is inhibited by the presence of sodium azide, suggesting the involvement of singlet oxygen in the process. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that treatment with FITC plus light induces crosslinks in viral envelope glycoproteins. Treatment of virions with high concentrations of FITC (50 ..mu..g/ml) plus light causes a reduction in the adsorption of the virus to monolayers of human embryonic lung cells. For lower concentrations of FITC (10 ..mu..g/ml) plus light, treated virions adsorb to the host cells, but remain sensitive to light until entry occurs. The loss of light sensitivity coincides with the development of resistance to antibodies. These results are most consistent with a mechanism of entry for herpes simplex virus involving fusion of the viral membrane with the plasma membrane of the host cell.

  14. Oncolytic virotherapy using herpes simplex virus: how far have we come?

    PubMed Central

    Sokolowski, Nicolas AS; Rizos, Helen; Diefenbach, Russell J

    2015-01-01

    Oncolytic virotherapy exploits the properties of human viruses to naturally cytolysis of cancer cells. The human pathogen herpes simplex virus (HSV) has proven particularly amenable for use in oncolytic virotherapy. The relative safety of HSV coupled with extensive knowledge on how HSV interacts with the host has provided a platform for manipulating HSV to enhance the targeting and killing of human cancer cells. This has culminated in the approval of talimogene laherparepvec for the treatment of melanoma. This review focuses on the development of HSV as an oncolytic virus and where the field is likely to head in the future. PMID:27512683

  15. Anisakis simplex larvae: infection status in marine fish and cephalopods purchased from the Cooperative Fish Market in Busan, Korea.

    PubMed

    Choi, Seon Hee; Kim, Jung; Jo, Jin Ok; Cho, Min Kyung; Yu, Hak Sun; Cha, Hee Jae; Ock, Mee Sun

    2011-03-01

    The infection status of marine fish and cephalopods with Anisakis simplex third stage larva (L3) was studied over a period of 1 year. A total of 2,537 specimens, which consisted of 40 species of fish and 3 species of cephalopods, were purchased from the Cooperative Fish Market in Busan, Korea, from August 2006 to July 2007. They were examined for A. simplex L3 from the whole body cavity, viscera, and muscles. A. simplex L3 were confirmed by light microscopy. The overall infection rate reached 34.3%, and average 17.1 larvae were parasitized per infected fish. Fish that recorded the highest infection rate was Lophiomus setigerus (100%), followed by Liparis tessellates (90%), Pleurogrammus azonus (90%), and Scomber japonicus (88.7%). The intensity of infection was the highest in Gadus macrocephalus (117.7 larvae per fish), followed by S. japonicus (103.9 larvae) and L. setigerus (54.2 larvae). Although abundance of A. simplex L3 was not seasonal in most of the fish species, 10 of the 16 selected species showed the highest abundance in February and April. A positive correlation between the intensity of L3 infection and the fish length was obvious in S. japonicus and G. macrocephalus. It was likely that A. simplex L3 are more frequently infected during the spring season in some species of fish. Our study revealed that eating raw or undercooked fish or cephalopods could still be a source of human infection with A. simplex L3 in Korea.

  16. Anisakis simplex Larvae: Infection Status in Marine Fish and Cephalopods Purchased from the Cooperative Fish Market in Busan, Korea

    PubMed Central

    Choi, Seon Hee; Kim, Jung; Jo, Jin Ok; Cho, Min Kyung; Yu, Hak Sun; Cha, Hee Jae

    2011-01-01

    The infection status of marine fish and cephalopods with Anisakis simplex third stage larva (L3) was studied over a period of 1 year. A total of 2,537 specimens, which consisted of 40 species of fish and 3 species of cephalopods, were purchased from the Cooperative Fish Market in Busan, Korea, from August 2006 to July 2007. They were examined for A. simplex L3 from the whole body cavity, viscera, and muscles. A. simplex L3 were confirmed by light microscopy. The overall infection rate reached 34.3%, and average 17.1 larvae were parasitized per infected fish. Fish that recorded the highest infection rate was Lophiomus setigerus (100%), followed by Liparis tessellates (90%), Pleurogrammus azonus (90%), and Scomber japonicus (88.7%). The intensity of infection was the highest in Gadus macrocephalus (117.7 larvae per fish), followed by S. japonicus (103.9 larvae) and L. setigerus (54.2 larvae). Although abundance of A. simplex L3 was not seasonal in most of the fish species, 10 of the 16 selected species showed the highest abundance in February and April. A positive correlation between the intensity of L3 infection and the fish length was obvious in S. japonicus and G. macrocephalus. It was likely that A. simplex L3 are more frequently infected during the spring season in some species of fish. Our study revealed that eating raw or undercooked fish or cephalopods could still be a source of human infection with A. simplex L3 in Korea. PMID:21461267

  17. Anisakis simplex larvae: infection status in marine fish and cephalopods purchased from the Cooperative Fish Market in Busan, Korea.

    PubMed

    Choi, Seon Hee; Kim, Jung; Jo, Jin Ok; Cho, Min Kyung; Yu, Hak Sun; Cha, Hee Jae; Ock, Mee Sun

    2011-03-01

    The infection status of marine fish and cephalopods with Anisakis simplex third stage larva (L3) was studied over a period of 1 year. A total of 2,537 specimens, which consisted of 40 species of fish and 3 species of cephalopods, were purchased from the Cooperative Fish Market in Busan, Korea, from August 2006 to July 2007. They were examined for A. simplex L3 from the whole body cavity, viscera, and muscles. A. simplex L3 were confirmed by light microscopy. The overall infection rate reached 34.3%, and average 17.1 larvae were parasitized per infected fish. Fish that recorded the highest infection rate was Lophiomus setigerus (100%), followed by Liparis tessellates (90%), Pleurogrammus azonus (90%), and Scomber japonicus (88.7%). The intensity of infection was the highest in Gadus macrocephalus (117.7 larvae per fish), followed by S. japonicus (103.9 larvae) and L. setigerus (54.2 larvae). Although abundance of A. simplex L3 was not seasonal in most of the fish species, 10 of the 16 selected species showed the highest abundance in February and April. A positive correlation between the intensity of L3 infection and the fish length was obvious in S. japonicus and G. macrocephalus. It was likely that A. simplex L3 are more frequently infected during the spring season in some species of fish. Our study revealed that eating raw or undercooked fish or cephalopods could still be a source of human infection with A. simplex L3 in Korea. PMID:21461267

  18. [Genetic susceptibility to herpes simplex encephalitis].

    PubMed

    Rozenberg, F

    2013-01-01

    Herpes simplex encephalitis (HSE) is a rare but severe complication of frequent and mostly benign infection with herpes simplex virus (HSV). Although rapid and sensitive diagnosis tools and active antiviral drugs are available, HSE morbidity/mortality levels remain unsatisfactory. Molecular and cellular determinants of HSE are incompletely understood. The rarity and severity of the disease have suggested an increased susceptibility of some subjects to HSV infection. Numerous experimental studies have investigated the respective role of host and viral factors in HSE. The results of these studies have illustrated the major role of the innate immune response, in particular interferons (IFNs), in limiting access of the virus into and/or virus replication in the central nervous system (CNS). In a few children with HSE, specific defects of the immune innate response have been identified, which impair the IFN-α/β and IFN-λ production of fibroblasts and/or neurons infected with HSV and render these cells more permissive to infection. The mutations affect proteins involved in the IFN pathway induced by stimulation of the TLR3 receptor. The patients' susceptibility to infection is restricted to HSV CNS invasion, underlining the major role of TLR3 in CNS protection against viral infection. The incomplete clinical penetrance of these molecular defects suggests that other factors (age, infectious dose) are involved in HSE. Whether pathogenesis of adult HSE is similar has not been investigated.

  19. Adeno-associated virus-mediated gene transfer targeting normal and traumatized mouse utricle.

    PubMed

    Wang, G-P; Guo, J-Y; Peng, Z; Liu, Y-Y; Xie, J; Gong, S-S

    2014-11-01

    Balance dysfunction is closely associated with loss of vestibular hair cells (HCs). Gene therapy shows promise when used to protect or regenerate vestibular HCs to preserve or restore adequate vestibular function. Adeno-associated virus (AAV) vectors allow long-term gene expression in the absence of toxicity. To noninvasively define an AAV serotype exhibiting favorable tropism toward the vestibular sensory epithelium, we characterized the transgene expression potential of AAV vectors (serotypes 1, 2, 5, 6 and 8) inoculated into adult mouse utricle via canalostomy. We found that AAV8 was the most effective AAV vector in utricular gene transfer. Swim tests and measurements of auditory brainstem response revealed minimal loss of vestibular function and hearing after canalostomy. In the normal utricle after AAV8 infusion, transduction efficiency peaked at 7 days, and was maintained thereafter, in vestibular HCs, and at 3 days in supporting cells (SCs). In the streptomycin-lesioned utricle, the SC transduction efficiency peaked at 7 days and decreased at 30 days. In conclusion, AAV8-mediated gene transfer via canalostomy facilitates efficient and safe transduction in mouse vestibular sensory epithelium, and may in the future become clinically relevant for human vestibular gene therapy. PMID:25119376

  20. Molecular and serologic diagnostic approaches; the prevalence of herpes simplex in idiopathic men infertile

    PubMed Central

    Amirjannati, Nasser; Yaghmaei, Farhad; Akhondi, Mohammad Mehdi; Nasiri, Mahboubeh; Heidari-Vala, Hamed; Sehhat, Zahra

    2014-01-01

    Background: Human pathogens that can cause infertility may also affect sperm count and quality. Viral infections can be considered as direct and/or indirect cause of male factor infertility. Objective: Our goal was to investigate the prevalence of herpes simplex virus in the semen of infertile men attending the Avicenna Infertility Clinic, and to compare it with the herpes virus serology results. Materials and Methods: This cross sectional study was conducted during 2009-2010. Infertile men participating without any clinical signs of infection with herpes simplex virus, and no obvious cause for their infertility were included. Semen and blood samples were used for Polymerase Chain Reaction (PCR) and serologic testing for these people. Two samples were collected: one ml semen sample to verify the existence of genital herpes simplex virus in infertile men, and blood samples of 217 individuals tested for antibodies to herpes simplex virus. Data were analyzed by SPSS 16. Results: According to the PCR results of semen samples the prevalence of herpes simplex in semen was 12% and serologic test showed 3.2% prevalence within blood. Nine to 10% of IgM negative were PCR positive and only 2-3% of IgM positive were PCR positive. Between herpes serologic studies with positive controls and negative controls by using both tests, there was a significant positive relationship (r=0.718 and p<0.001). The relationship between semen PCR test results and serological survey of herpes patients with a negative control in both Pearson and Spearman tests was positive and significant (r=0.229 and p=0.001). Correlation between the PCR results of semen samples with two positive control subjects and a positive IgM test was statistically confirmed (r=0.235 and p<0.001). Conclusion: We recommend that if there is suspicion to herpes simplex as a microorganism that theoretically could impact semen parameters and cause infertility it is prudent to use PCR technique on semen sample rather than ELISA

  1. Inhibitors of nucleotidyltransferase superfamily enzymes suppress herpes simplex virus replication.

    PubMed

    Tavis, John E; Wang, Hong; Tollefson, Ann E; Ying, Baoling; Korom, Maria; Cheng, Xiaohong; Cao, Feng; Davis, Katie L; Wold, William S M; Morrison, Lynda A

    2014-12-01

    Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five compounds in two chemical families inhibited HSV replication in Vero and human foreskin fibroblast cells as well as the approved drug acyclovir did. The compounds had 50% effective concentration values as low as 0.22 μM with negligible cytotoxicity in the assays employed. The inhibitors suppressed accumulation of viral genomes and infectious particles and blocked events in the viral replication cycle before and during viral DNA replication. Acyclovir-resistant mutants of HSV-1 and HSV-2 remained highly sensitive to the NTS inhibitors. Five of six NTS inhibitors of the HSVs also blocked replication of another herpesvirus pathogen, human cytomegalovirus. Therefore, NTS enzyme inhibitors are promising candidates for new herpesvirus treatments that may have broad efficacy against members of the herpesvirus family.

  2. Role of CD137 signaling in dengue virus-mediated apoptosis

    SciTech Connect

    Nagila, Amar; Netsawang, Janjuree; Srisawat, Chatchawan; Noisakran, Sansanee; Morchang, Atthapan; Yasamut, Umpa; Puttikhunt, Chunya; Kasinrerk, Watchara; and others

    2011-07-08

    Highlights: {yields} For the first time the role of CD137 in dengue virus (DENV) infection. {yields} Induction of DENV-mediated apoptosis by CD137 signaling. {yields} Sensitization to CD137-mediated apoptosis by dengue virus capsid protein (DENV C). {yields} Nuclear localization of DENV C is required for CD137-mediated apoptosis. -- Abstract: Hepatic dysfunction is a well recognized feature of dengue virus (DENV) infection. However, molecular mechanisms of hepatic injury are still poorly understood. A complex interaction between DENV and the host immune response contributes to DENV-mediated tissue injury. DENV capsid protein (DENV C) physically interacts with the human death domain-associated protein Daxx. A double substitution mutation in DENV C (R85A/K86A) abrogates Daxx interaction, nuclear localization and apoptosis. Therefore we compared the expression of cell death genes between HepG2 cells expressing DENV C and DENV C (R85A/K86A) using a real-time PCR array. Expression of CD137, which is a member of the tumor necrosis factor receptor family, increased significantly in HepG2 cells expressing DENV C compared to HepG2 cells expressing DENV C (R85A/K86A). In addition, CD137-mediated apoptotic activity in HepG2 cells expressing DENV C was significantly increased by anti-CD137 antibody compared to that of HepG2 cells expressing DENV C (R85A/K86A). In DENV-infected HepG2 cells, CD137 mRNA and CD137 positive cells significantly increased and CD137-mediated apoptotic activity was increased by anti-CD137 antibody. This work is the first to demonstrate the contribution of CD137 signaling to DENV-mediated apoptosis.

  3. Immunomodulation with IL-4R alpha antisense oligonucleotide prevents respiratory syncytial virus-mediated pulmonary disease.

    PubMed

    Ripple, Michael J; You, Dahui; Honnegowda, Srinivasa; Giaimo, Joseph D; Sewell, Andrew B; Becnel, David M; Cormier, Stephania A

    2010-10-15

    Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Severe RSV infections in infants cause bronchiolitis, wheeze, and/or cough and significantly increase the risk for developing asthma. RSV pathogenesis is thought to be due to a Th2-type immune response initiated in response to RSV infection, specifically in the infant. Using a neonatal mouse system as an appropriate model for human infants, we sought to determine whether local inhibition of IL-4Rα expression during primary RSV infection in the neonate would prevent Th2-skewed responses to secondary RSV infection and improve long-term pulmonary function. To reduce IL-4Rα expression, antisense oligonucleotides (ASOs) specific for IL-4Rα were administered intranasally to neonatal mice at the time of primary infection. Mice were initially infected with RSV at 1 wk of age and were reinfected at 6 wk of age. Administration of IL-4Rα ASOs during primary RSV infection in neonatal mice abolished the pulmonary dysfunction normally observed following reinfection in the adult. This ablation of pulmonary dysfunction correlated with a persistent rebalancing of the Th cell compartment with decreased Th2 responses (i.e., reduced goblet cell hyperplasia, Th2 cells, and cytokine secretion) and increased Th1 responses (i.e., elevated Th1 cell numbers and type I Abs and cytokines). Our data support our hypothesis that a reduction in the Th2 immune response during primary infection in neonates prevents Th2-mediated pulmonary pathology initially and upon reinfection and further suggest that vaccine strategies incorporating IL-4Rα ASOs may be of significant benefit to infants.

  4. [Neonatal herpes simplex encephalitis: clinical profile versus molecular biology].

    PubMed

    Izquierdo, Giannina; Cofré, José; Torres, J Pablo; Venegas, Gerardo; Vergara, Alejandra; Farfán, Mauricio

    2012-08-01

    Herpes simplex encephalitis is a diagnostic challenge and causes high morbidity and mortality in children. Early suspicion of the disease and a rapid, safe and useful diagnostic test are relevant because up to 70% of the cases may die. We report the case of a newborn girl aged 25 days, who presented with a clinical picture that was compatible with herpes simplex encephalitis where the confirmation of the etiological diagnosis was delayed. Only by repeated real-time polymerase chain reaction it was possible to confirm the presence of herpes simplex virus type 1 in the cerebrospinal fluid.

  5. Kernel simplex growing algorithm for hyperspectral endmember extraction

    NASA Astrophysics Data System (ADS)

    Zhao, Liaoying; Zheng, Junpeng; Li, Xiaorun; Wang, Lijiao

    2014-01-01

    In order to effectively extract endmembers for hyperspectral imagery where linear mixing model may not be appropriate due to multiple scattering effects, this paper extends the simplex growing algorithm (SGA) to its kernel version. A new simplex volume formula without dimension reduction is used in SGA to form a new simplex growing algorithm (NSGA). The original data are nonlinearly mapped into a high-dimensional space where the scatters can be ignored. To avoid determining complex nonlinear mapping, a kernel function is used to extend the NSGA to kernel NSGA (KNSGA). Experimental results of simulated and real data prove that the proposed KNSGA approach outperforms SGA and NSGA.

  6. Vaccinia Virus Recombinant Expressing Herpes Simplex Virus Type 1 Glycoprotein D Prevents Latent Herpes in Mice

    NASA Astrophysics Data System (ADS)

    Cremer, Kenneth J.; Mackett, Michael; Wohlenberg, Charles; Notkins, Abner Louis; Moss, Bernard

    1985-05-01

    In humans, herpes simplex virus causes a primary infection and then often a latent ganglionic infection that persists for life. Because these latent infections can recur periodically, vaccines are needed that can protect against both primary and latent herpes simplex infections. Infectious vaccinia virus recombinants that contain the herpes simplex virus type 1 (HSV-1) glycoprotein D gene under control of defined early or late vaccinia virus promoters were constructed. Tissue culture cells infected with these recombinant viruses synthesized a glycosylated protein that had the same mass (60,000 daltons) as the glycoprotein D produced by HSV-1. Immunization of mice with one of these recombinant viruses by intradermal, subcutaneous, or intraperitoneal routes resulted in the production of antibodies that neutralized HSV-1 and protected the mice against subsequent lethal challenge with HSV-1 or HSV-2. Immunization with the recombinant virus also protected the majority of the mice against the development of a latent HSV-1 infection of the trigeminal ganglia. This is the first demonstration that a genetically engineered vaccine can prevent the development of latency.

  7. Optimization using the gradient and simplex methods.

    PubMed

    Cerdà, Víctor; Cerdà, Juan Luis; Idris, Abubakr M

    2016-02-01

    Traditionally optimization of analytical methods has been conducted using a univariate method, varying each parameter one-by-one holding fixed the remaining. This means in many cases to reach only local minima and not get the real optimum. Among the various options for multivariate optimization, this paper highlights the gradient method, which involves the ability to perform the partial derivatives of a mathematical model, as well as the simplex method that does not require that condition. The advantages and disadvantages of those two multivariate optimization methods are discussed, indicating when they can be applied and the different forms that have been introduced. Different cases are described on the applications of these methods in analytical chemistry. PMID:26653495

  8. Selective language aphasia from herpes simplex encephalitis.

    PubMed

    Ku, A; Lachmann, E A; Nagler, W

    1996-09-01

    We report the case of a 16-year-old right-handed Chinese/English bilingual patient who developed herpes simplex encephalitis involving the left temporal lobe, with resultant aphasia. His native language was Mandarin, but he had received extensive training in English for 6 years after moving to the United States and was fluent in English. One week after admission, he could not speak, comprehend, repeat, name, read, or write in English, but he had relative preservation of most of these facilities in Mandarin. He could not write in Mandarin, and his syntax was simplified. Two months later, along with intensive bilingual speech therapy, his reading, writing, and naming in English had almost recovered.

  9. The varicella-zoster virus-mediated delayed host shutoff: open reading frame 17 has no major function, whereas immediate-early 63 protein represses heterologous gene expression.

    PubMed

    Desloges, Nathalie; Rahaus, Markus; Wolff, Manfred H

    2005-12-01

    We reported that varicella-zoster virus (VZV) causes a delayed host shutoff during its replicative cycle. VZV open reading frame 17 (ORF17) is the homologue of the herpes simplex virus (HSV) UL41 gene encoding the virion host shutoff (vhs) protein which is responsible for the shutoff effect observed in HSV-infected cells. In the present study, we demonstrated that ORF17 is expressed as a late protein during the VZV replicative cycle in different infected permissive cell lines which showed a delayed shutoff of cellular RNA. A cell line with stable expression of VZV ORF17 was infected with VZV. In these cells, VZV replication and delayed host shutoff remained unchanged when compared to normal infected cells. ORF17 was not capable of repressing the expression of the beta-gal reporter gene under the control of the human cytomegalovirus immediate-early gene promoter or to inhibit the expression of a CAT reporter gene under the control of the human GAPDH promoter, indicating that ORF17 has no major function in the VZV-mediated delayed host shutoff. To determine whether other viral factors are involved in the host shutoff, a series of cotransfection assays was performed. We found that the immediate-early 63 protein (IE63) was able to downregulate the expression of reporter genes under the control of the two heterologous promoters, indicating that this viral factor can be involved in the VZV-mediated delayed host shutoff. Other factors can be also implicated to modulate the repressing action of IE63 to achieve a precise balance between the viral and cellular gene expression.

  10. Herpes simplex virus type 1-derived recombinant and amplicon vectors.

    PubMed

    Fraefel, Cornel; Marconi, Peggy; Epstein, Alberto L

    2011-01-01

    Herpes simplex virus type 1 (HSV-1) is a human pathogen whose lifestyle is based on a long-term dual interaction with the infected host, being able to establish both lytic and latent infections. The virus genome is a 153 kbp double-stranded DNA molecule encoding more than 80 genes. The interest of HSV-1 as gene transfer vector stems from its ability to infect many different cell types, both quiescent and proliferating cells, the very high packaging capacity of the virus capsid, the outstanding neurotropic adaptations that this virus has evolved, and the fact that it never integrates into the cellular chromosomes, thus avoiding the risk of insertional mutagenesis. Two types of vectors can be derived from HSV-1, recombinant vectors and amplicon vectors, and different methodologies have been developed to prepare large stocks of each type of vector. This chapter summarizes (1) the two approaches most commonly used to prepare recombinant vectors through homologous recombination, either in eukaryotic cells or in bacteria, and (2) the two methodologies currently used to generate helper-free amplicon vectors, either using a bacterial artificial chromosome (BAC)-based approach or a Cre/loxP site-specific recombination strategy.

  11. Recent progress in herpes simplex virus immunobiology and vaccine research.

    PubMed

    Koelle, David M; Corey, Lawrence

    2003-01-01

    Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) cause prevalent, chronic infections that have serious outcomes in some individuals. Neonatal herpes may occur when the infant traverses the cervix during maternal genital herpes. Genital herpes is a major risk factor for human immunodeficiency virus type 1 transmission. Considerable efforts have been made to design and test vaccines for HSV, focusing on genital infection with HSV-2. Several protein subunit vaccines based on HSV-2 envelope glycoproteins have reached advanced-phase clinical trials. These antigens were chosen because they are the targets of neutralizing-antibody responses and because they elicit cellular immunity. Encouraging results have been reported in studies of treatment of HSV-seronegative women with a vaccine consisting of truncated glycoprotein D of HSV-2 and a novel adjuvant. Because most sexual HSV transmission occurs during asymptomatic shedding, it is important to evaluate the impact of vaccination on HSV-2 infection, clinically apparent genital herpes, and HSV shedding among vaccine recipients who acquire infection. There are several other attractive formats, including subunit vaccines that target cellular immune responses, live attenuated virus strains, and mutant strains that undergo incomplete lytic replication. HSV vaccines have also been evaluated for the immunotherapy of established HSV infection. PMID:12525427

  12. ELISA for herpes simplex virus (HSV) type-specific antibodies in human sera using HSV type 1 and type 2 polyspecific antigens blocked with type-heterologous rabbit antibodies.

    PubMed

    Vestergaard, B F; Grauballe, P C

    1979-08-01

    Crude antigenic preparations made from rabbit cornea cells infected with either HSV type 1 or type 2 could be used in ELISA for titration of HSV type-specific antibodies in human sera. After immunochemical binding of the crude HSV antigens in microtitre wells by use of type-homologous rabbit antibodies, type-common antigenic sties were blocked with type-heterologous rabbit antibodies. Titration of human sera in this system showed that high concentrations of type heterologous rabbit antibodies were capable of completely blocking type-common antigenic sites, while leaving type-specific antigenic sites unblocked and capable of reacting with human antibodies. Thus HSV type-specific antibodies in human sera could be measured in ELISA without the use of purified typespecific antigens.

  13. Prospects and Perspectives for Development of a Vaccine Against Herpes Simplex Virus Infections

    PubMed Central

    McAllister, Shane C.; Schleiss, Mark R.

    2014-01-01

    Herpes simplex viruses 1 and -2 are human pathogens that lead to significant morbidity and mortality in certain clinical settings. The development of effective antiviral medications, however, has had little discernible impact on the epidemiology of these pathogens, largely because the majority of infections are clinically silent. Decades of work have gone into various candidate HSV vaccines, but to date none has demonstrated sufficient efficacy to warrant licensure. This review examines developments in HSV immunology and vaccine development published since 2010, and assesses the prospects for improved immunization strategies that may result in an effective, licensed vaccine in the near future. PMID:25077372

  14. Prospects and perspectives for development of a vaccine against herpes simplex virus infections.

    PubMed

    McAllister, Shane C; Schleiss, Mark R

    2014-11-01

    Herpes simplex viruses 1 and 2 are human pathogens that lead to significant morbidity and mortality in certain clinical settings. The development of effective antiviral medications, however, has had little discernible impact on the epidemiology of these pathogens, largely because the majority of infections are clinically silent. Decades of work have gone into various candidate HSV vaccines, but to date none has demonstrated sufficient efficacy to warrant licensure. This review examines developments in HSV immunology and vaccine development published since 2010, and assesses the prospects for improved immunization strategies that may result in an effective, licensed vaccine in the near future.

  15. Experimental investigation of herpes simplex virus latency.

    PubMed Central

    Wagner, E K; Bloom, D C

    1997-01-01

    The clinical manifestations of herpes simplex virus infection generally involve a mild and localized primary infection followed by asymptomatic (latent) infection interrupted sporadically by periods of recrudescence (reactivation) where virus replication and associated cytopathologic findings are manifest at the site of initial infection. During the latent phase of infection, viral genomes, but not infectious virus itself, can be detected in sensory and autonomic neurons. The process of latent infection and reactivation has been subject to continuing investigation in animal models and, more recently, in cultured cells. The initiation and maintenance of latent infection in neurons are apparently passive phenomena in that no virus gene products need be expressed or are required. Despite this, a single latency-associated transcript (LAT) encoded by DNA encompassing about 6% of the viral genome is expressed during latent infection in a minority of neurons containing viral DNA. This transcript is spliced, and the intron derived from this splicing is stably maintained in the nucleus of neurons expressing it. Reactivation, which can be induced by stress and assayed in several animal models, is facilitated by the expression of LAT. Although the mechanism of action of LAT-mediated facilitation of reactivation is not clear, all available evidence argues against its involving the expression of a protein. Rather, the most consistent models of action involve LAT expression playing a cis-acting role in a very early stage of the reactivation process. PMID:9227860

  16. Sensitization to Anisakis simplex: an unusual presentation.

    PubMed

    Estrada Rodríguez, J L; Gozalo Reques, F

    1997-01-01

    It has recently been published patients suffering from urticaria or anaphylaxia induced by nematodes usually parasitizing fishs or cephalopode, in whom, Anisakis simplex (AK) sensitization prevalence was detected up to 37%. We tried out a prospective study to evaluate the presence of AK specific-IgE in an asthmatic population, comparing to other group of patients with urticaria. Complaints related to food ingestion were recorded in both, and dietetic measures were advised. Thirteen patients (13/66; 20%) showed AK specific IgE. Nine of them were asthmatics (p < 0.01), and only 4 suffered from urticaria. Four patients, three of them asthmatics, could link symptoms after fishs, cephalopode or, surprisingly, seafood intake, including epigastralgia, rhinorrhea, conjunctivitis, hives, and dyspnea. Atopia was not a consistent status, only five AK sensitized patients also did to common inhalants (all skin prick-test positive to house dust mites). Asthmatic AK-sensitized patients were older than non AK-sensitized asthmatics (46.23 vs 30.1; p < 0.05). The way of sensitization could be inhalative or through digestive mucosa parasitization by live larvae. Possibility that an AK allergen can play a role in adult asthma, should be considered specially in countries with high fish or seafood diet content.

  17. Mycosis inhibits cannibalism by Melanoplus sanguinipes, M. differentialis, Schistocerca americana, and Anabrus simplex

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cannibalism is common among the Acrididae and the Mormon cricket, Anabrus simplex, a tettigonid. These behaviors have been proposed as mechanisms for the horizontal transmission of Microsporida and entomopathogenic fungi. After anecdotal observations that Melanoplus sanguinipes and A. simplex did ...

  18. Expression of Genes Encoding the Enzymes for Glycogen and Trehalose Metabolism in L3 and L4 Larvae of Anisakis simplex

    PubMed Central

    Łopieńska-Biernat, E.; Zaobidna, E. A.; Dmitryjuk, M.

    2015-01-01

    Trehalose and glycogen metabolism plays an important role in supporting life processes in many nematodes, including Anisakis simplex. Nematodes, cosmopolitan helminths parasitizing sea mammals and humans, cause a disease known as anisakiasis. The aim of this study was to investigate the expression of genes encoding the enzymes involved in the metabolism of trehalose and glycogen—trehalose-6-phosphate synthase (TPS), trehalose-6-phosphate phosphatase (TPP), glycogen synthase (GS), and glycogen phosphorylase (GP)—in stage L3 and stage L4 larvae of A. simplex. The expression of mRNA all four genes, tps, tpp, gs, and gp, was examined by real-time polymerase chain reaction. The A. simplex ribosomal gene (18S) was used as a reference gene. Enzymatic activity was determined. The expression of trehalose enzyme genes was higher in L3 than in L4 larvae, but an inverse relationship was noted for the expression of gs and gp genes. PMID:26783451

  19. Dynasore Disrupts Trafficking of Herpes Simplex Virus Proteins

    PubMed Central

    Mues, Mascha B.; Cheshenko, Natalia; Wilson, Duncan W.; Gunther-Cummins, Leslie

    2015-01-01

    ABSTRACT Dynasore, a small-molecule inhibitor of the GTPase activity of dynamin, inhibits the entry of several viruses, including herpes simplex virus (HSV), but its impact on other steps in the viral life cycle has not been delineated. The current study was designed to test the hypothesis that dynamin is required for viral protein trafficking and thus has pleiotropic inhibitory effects on HSV infection. Dynasore inhibited HSV-1 and HSV-2 infection of human epithelial and neuronal cells, including primary genital tract cells and human fetal neurons and astrocytes. Similar results were obtained when cells were transfected with a plasmid expressing dominant negative dynamin. Kinetic studies demonstrated that dynasore reduced the number of viral capsids reaching the nuclear pore if added at the time of viral entry and that, when added as late as 8 h postentry, dynasore blocked the transport of newly synthesized viral proteins from the nucleus to the cytosol. Proximity ligation assays demonstrated that treatment with dynasore prevented the colocalization of VP5 and dynamin. This resulted in a reduction in the number of viral capsids isolated from sucrose gradients. Fewer capsids were observed by electron microscopy in dynasore-treated cells than in control-treated cells. There were also reductions in infectious progeny released into culture supernatants and in cell-to-cell spread. Together, these findings suggest that targeting dynamin-HSV interactions may provide a new strategy for HSV treatment and prevention. IMPORTANCE HSV infections remain a global health problem associated with significant morbidity, particularly in neonates and immunocompromised hosts, highlighting the need for novel approaches to treatment and prevention. The current studies indicate that dynamin plays a role in multiple steps in the viral life cycle and provides a new target for antiviral therapy. Dynasore, a small-molecule inhibitor of dynamin, has pleiotropic effects on HSV-1 and HSV-2

  20. Striated muscle involvement in experimental oral infection by herpes simplex virus type 1.

    PubMed

    Gonzalez, María Inés; Sanjuan, Norberto A

    2013-07-01

    Herpes simplex virus type 1 is one of the most frequent causes of oral infection in humans, especially during early childhood. Several experimental models have been developed to study the pathogenesis of this virus but all of them employed adult animals. In this work, we developed an experimental model that uses mice younger than 4 days old, to more closely resemble human infection. Mice were infected subcutaneously with the prototype strain McIntyre of Herpes simplex-1, and the progression of infection was studied by immunoperoxidase. All animals died within 24-72 h post-infection, while viral antigens were found in the oral epithelium, nerves and brain. The most striking result was the finding of viral antigens in the nucleus and cytoplasm of cells belonging to striated muscles. Organotypic cultures of striated muscles were performed, and viral replication was observed in them by immunocytochemistry, electron microscopy and viral isolation. We conclude that the infection of striated muscles is present from the onset of oral infection and, eventually, could explain some clinical observations in humans.

  1. Herpes simplex virus virion host shutoff function.

    PubMed

    Kwong, A D; Kruper, J A; Frenkel, N

    1988-03-01

    Herpes simplex virus (HSV) virions contain one or more functions which mediate the shutoff of host protein synthesis and the degradation of host mRNA. HSV type 1 (HSV-1) mutants deficient in the virion shutoff of host protein synthesis (vhs mutants) were isolated and were found to be defective in their ability to degrade host mRNA. Furthermore, it was found that viral mRNAs in cells infected with the vhs 1 mutant have a significantly longer functional half-life than viral mRNAs in wild-type virus-infected cells. In the present study we have mapped the vhs1 mutation affecting the virion shutoff of host protein synthesis to a 265-base-pair NruI-XmaIII fragment spanning map coordinates 0.604 to 0.606 of the HSV-1 genome. The mutation(s) affecting the functional half-lives of host mRNA as well as the alpha (immediate-early), beta (early), and gamma (late) viral mRNAs were also mapped within this 265-base-pair fragment. Thus, the shutoff of host protein synthesis is most likely mediated by the same function which decreases the half-life of viral mRNA. The shorter half-life of infected-cell mRNAs may allow a more rapid modulation of viral gene expression in response to changes in the transcription of viral genes. Interestingly, the vhs1 mutation of HSV-1 maps within a region which overlaps the Bg/II-N sequences of HSV-2 DNA shown previously to transform cells in culture. The possible relationship between the transformation and host shutoff functions are discussed.

  2. Herpes simplex virus virion host shutoff function.

    PubMed Central

    Kwong, A D; Kruper, J A; Frenkel, N

    1988-01-01

    Herpes simplex virus (HSV) virions contain one or more functions which mediate the shutoff of host protein synthesis and the degradation of host mRNA. HSV type 1 (HSV-1) mutants deficient in the virion shutoff of host protein synthesis (vhs mutants) were isolated and were found to be defective in their ability to degrade host mRNA. Furthermore, it was found that viral mRNAs in cells infected with the vhs 1 mutant have a significantly longer functional half-life than viral mRNAs in wild-type virus-infected cells. In the present study we have mapped the vhs1 mutation affecting the virion shutoff of host protein synthesis to a 265-base-pair NruI-XmaIII fragment spanning map coordinates 0.604 to 0.606 of the HSV-1 genome. The mutation(s) affecting the functional half-lives of host mRNA as well as the alpha (immediate-early), beta (early), and gamma (late) viral mRNAs were also mapped within this 265-base-pair fragment. Thus, the shutoff of host protein synthesis is most likely mediated by the same function which decreases the half-life of viral mRNA. The shorter half-life of infected-cell mRNAs may allow a more rapid modulation of viral gene expression in response to changes in the transcription of viral genes. Interestingly, the vhs1 mutation of HSV-1 maps within a region which overlaps the Bg/II-N sequences of HSV-2 DNA shown previously to transform cells in culture. The possible relationship between the transformation and host shutoff functions are discussed. Images PMID:2828686

  3. Retargeting Strategies for Oncolytic Herpes Simplex Viruses

    PubMed Central

    Campadelli-Fiume, Gabriella; Petrovic, Biljana; Leoni, Valerio; Gianni, Tatiana; Avitabile, Elisa; Casiraghi, Costanza; Gatta, Valentina

    2016-01-01

    Most of the oncolytic herpes simplex viruses (HSVs) exhibit a high safety profile achieved through attenuation. They carry defects in virulence proteins that antagonize host cell response to the virus, including innate response, apoptosis, authophagy, and depend on tumor cell proliferation. They grow robustly in cancer cells, provided that these are deficient in host cell responses, which is often the case. To overcome the attenuation limits, a strategy is to render the virus highly cancer-specific, e.g., by retargeting their tropism to cancer-specific receptors, and detargeting from natural receptors. The target we selected is HER-2, overexpressed in breast, ovarian and other cancers. Entry of wt-HSV requires the essential glycoproteins gD, gH/gL and gB. Here, we reviewed that oncolytic HSV retargeting was achieved through modifications in gD: the addition of a single-chain antibody (scFv) to HER-2 coupled with appropriate deletions to remove part of the natural receptors’ binding sites. Recently, we showed that also gH/gL can be a retargeting tool. The insertion of an scFv to HER-2 at the gH N-terminus, coupled with deletions in gD, led to a recombinant capable to use HER-2 as the sole receptor. The retargeted oncolytic HSVs can be administered systemically by means of carrier cells-forcedly-infected mesenchymal stem cells. Altogether, the retargeted oncolytic HSVs are highly cancer-specific and their replication is not dependent on intrinsic defects of the tumor cells. They might be further modified to express immunomodulatory molecules. PMID:26927159

  4. Simplex-stochastic collocation method with improved scalability

    NASA Astrophysics Data System (ADS)

    Edeling, W. N.; Dwight, R. P.; Cinnella, P.

    2016-04-01

    The Simplex-Stochastic Collocation (SSC) method is a robust tool used to propagate uncertain input distributions through a computer code. However, it becomes prohibitively expensive for problems with dimensions higher than 5. The main purpose of this paper is to identify bottlenecks, and to improve upon this bad scalability. In order to do so, we propose an alternative interpolation stencil technique based upon the Set-Covering problem, and we integrate the SSC method in the High-Dimensional Model-Reduction framework. In addition, we address the issue of ill-conditioned sample matrices, and we present an analytical map to facilitate uniformly-distributed simplex sampling.

  5. SIMPLEX: simulator and postprocessor for free-electron laser experiments

    PubMed Central

    Tanaka, Takashi

    2015-01-01

    SIMPLEX is a computer program developed for simulating the amplification process of free-electron lasers (FELs). It numerically solves the so-called FEL equations describing the evolution of the radiation field and growth of microbunching while the electron beam travels along the undulator. In order to reduce the numerical cost, the FEL equations have been reduced to more convenient forms for numerical implementation by applying reasonable approximations. SIMPLEX is equipped with a postprocessor to facilitate the retrieval of desired information from the simulation results, which is crucial for practical applications such as designing the beamline and analyzing the experimental results. PMID:26289287

  6. Primary herpes simplex virus infection mimicking cervical cancer.

    PubMed

    Tomkins, Andrew; White, Catherine; Higgins, Stephen Peter

    2015-06-02

    We report the case of an 18-year-old woman presenting with ulceration of the cervix caused by primary type 2 herpes simplex infection in the absence of skin lesions. The differential diagnosis included cervical cancer and we referred the patient for urgent colposcopy. However, laboratory tests proved the viral aetiology of the cervical ulceration and the cervix had healed completely 3 weeks later. The case highlights the need to consider herpes simplex infection in the differential diagnosis of ulceration of the cervix even when there are no cutaneous signs of herpes.

  7. Replication-Competent Controlled Herpes Simplex Virus

    PubMed Central

    Bloom, David C.; Feller, Joyce; McAnany, Peterjon; Vilaboa, Nuria

    2015-01-01

    ABSTRACT We present the development and characterization of a replication-competent controlled herpes simplex virus 1 (HSV-1). Replication-essential ICP4 and ICP8 genes of HSV-1 wild-type strain 17syn+ were brought under the control of a dually responsive gene switch. The gene switch comprises (i) a transactivator that is activated by a narrow class of antiprogestins, including mifepristone and ulipristal, and whose expression is mediated by a promoter cassette that comprises an HSP70B promoter and a transactivator-responsive promoter and (ii) transactivator-responsive promoters that drive the ICP4 and ICP8 genes. Single-step growth experiments in different cell lines demonstrated that replication of the recombinant virus, HSV-GS3, is strictly dependent on an activating treatment consisting of administration of a supraphysiological heat dose in the presence of an antiprogestin. The replication-competent controlled virus replicates with an efficiency approaching that of the wild-type virus from which it was derived. Essentially no replication occurs in the absence of activating treatment or if HSV-GS3-infected cells are exposed only to heat or antiprogestin. These findings were corroborated by measurements of amounts of viral DNA and transcripts of the regulated ICP4 gene and the glycoprotein C (gC) late gene, which was not regulated. Similar findings were made in experiments with a mouse footpad infection model. IMPORTANCE The alphaherpesviruses have long been considered vectors for recombinant vaccines and oncolytic therapies. The traditional approach uses vector backbones containing attenuating mutations that restrict replication to ensure safety. The shortcoming of this approach is that the attenuating mutations tend to limit both the immune presentation and oncolytic properties of these vectors. HSV-GS3 represents a novel type of vector that, when activated, replicates with the efficiency of a nonattenuated virus and whose safety is derived from deliberate

  8. Structural basis for the antibody neutralization of Herpes simplex virus

    SciTech Connect

    Lee, Cheng-Chung; Lin, Li-Ling; Chan, Woan-Eng; Ko, Tzu-Ping; Lai, Jiann-Shiun; Wang, Andrew H.-J.

    2013-10-01

    The gD–E317-Fab complex crystal revealed the conformational epitope of human mAb E317 on HSV gD, providing a molecular basis for understanding the viral neutralization mechanism. Glycoprotein D (gD) of Herpes simplex virus (HSV) binds to a host cell surface receptor, which is required to trigger membrane fusion for virion entry into the host cell. gD has become a validated anti-HSV target for therapeutic antibody development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was previously raised against HSV gD for viral neutralization. To understand the structural basis of antibody neutralization, crystals of the gD ectodomain bound to the E317 Fab domain were obtained. The structure of the complex reveals that E317 interacts with gD mainly through the heavy chain, which covers a large area for epitope recognition on gD, with a flexible N-terminal and C-terminal conformation. The epitope core structure maps to the external surface of gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD–nectin-1 interface and occludes the HVEM contact site of gD to block its binding to either receptor. The binding of E317 to gD also prohibits the formation of the N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD overlaps with either the nectin-1-binding residues or the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD for E317 binding are highly conserved between two types of human herpesvirus (HSV-1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated with the receptor-binding regions. The results further strengthen the previously demonstrated therapeutic and diagnostic potential of the E317 antibody.

  9. Mollaret's meningitis and herpes simplex virus type 2 infections.

    PubMed

    Farazmand, P; Woolley, P D; Kinghorn, G R

    2011-06-01

    Benign recurrent aseptic meningitis is a rare disorder described by Mollaret in 1944. When initially described, this form of aseptic meningitis had no identifiable infecting agent. New sophisticated diagnostic tools have now identified herpes simplex type 2 virus as the most commonly isolated agent. Antiviral treatment has been used successfully for prophylaxis and treatment.

  10. The Law of Cosines for an "n"-Dimensional Simplex

    ERIC Educational Resources Information Center

    Ding, Yiren

    2008-01-01

    Using the divergence theorem technique of L. Eifler and N.H. Rhee, "The n-dimensional Pythagorean Theorem via the Divergence Theorem" (to appear: Amer. Math. Monthly), we extend the law of cosines for a triangle in a plane to an "n"-dimensional simplex in an "n"-dimensional space.

  11. Prevalence of herpes simplex virus disease in a professional population.

    PubMed

    Brooks, S L; Rowe, N H; Drach, J C; Shipman, C; Young, S K

    1981-01-01

    By virtue of occupation, dentists are frequently exposed to the herpes simplex virus. The risk of infection by the virus was evaluated by assessing disease experience as shown by history compared with the results of complement fixing or antibody titration tests, or both.

  12. Nonlinear and Quasi-Simplex Patterns in Latent Growth Models

    ERIC Educational Resources Information Center

    Bianconcini, Silvia

    2012-01-01

    In the SEM literature, simplex and latent growth models have always been considered competing approaches for the analysis of longitudinal data, even if they are strongly connected and both of specific importance. General dynamic models, which simultaneously estimate autoregressive structures and latent curves, have been recently proposed in the…

  13. Argument Structure of Tsou: Simplex and Complex Predicates

    ERIC Educational Resources Information Center

    Lin, Gujing

    2010-01-01

    This thesis investigates the argument structure of Tsou, a Formosan language within the Austronesian family. The investigation studies both simplex and complex predicates as well as describes the valency groupings and alignment patterns emerging from various clausal configurations. Assuming the stance that language description should respect…

  14. Predicting a Longitudinal Guttman Simplex of Adolescent Substance Use.

    ERIC Educational Resources Information Center

    McGuigan, Kimberly A.; And Others

    The longitudinal Guttman simplex (LGS), a method of modeling stage sequences or levels over time, allows for individual differences in sequence progression or development. The LGS is particularly appropriate in modeling tobacco, alcohol, and marijuana use stages with adolescent subjects where relationships among drugs and degree of involvement may…

  15. The N-Simplex and Its Generalizations towards Fractals

    ERIC Educational Resources Information Center

    Kosi-Ulbl, Irena; Pagon, Dusan

    2002-01-01

    Nature is full of different crystals and many of them have shapes of regular geometric objects. Those in which the fractal structure of a geometric object can be recognized are especially unusual. In this paper a generalization of one of these shapes is described: a formation, based on an n-dimensional simplex. The construction of an n-dimensional…

  16. [Herpes simplex virus hepatitis; rare in immunocompetent patients].

    PubMed

    Ozokcu, Leyla; de Bruijckere, Leo M; Jansen, Jan; van den Berge, Marcel

    2009-01-01

    A 42-year-old woman was referred with fever and abdominal pain with peritoneal irritation. A diagnostic laparoscopy showed hepatic lesions. Histopathological investigation of the liver biopsy showed hepatitis caused by herpes simplex virus (HSV). The patient was treated with acyclovir and recovered well. HSV is a rare cause of viral hepatitis and has a high mortality rate.

  17. Prevalence of Herpes Simplex Virus Antibodies in Dental Students.

    ERIC Educational Resources Information Center

    Rodu, Brad; And Others

    1992-01-01

    A study of 125 sophomore preclinical dental students found that these young professionals, because of having a low prevalence of herpes simplex virus (HSV) antibodies, are at risk for acquiring a primary HSV infection when treating HSV positive patients and should take precautions to avoid virus transmission. (MSE)

  18. The "Other" Venereal Diseases: Herpes Simplex, Trichomoniasis and Candidiasis.

    ERIC Educational Resources Information Center

    McNab, Warren L.

    1979-01-01

    Although the term venereal disease has been synonymous with gonorrhea and syphilis, the Center for Disease Control now states that the number of new cases of herpes simplex, trichomoniasis, and candidiasis is rapidly approaching the number of cases of syphilis and gonorrhea. (MM)

  19. Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management.

    PubMed

    Bradshaw, Michael J; Venkatesan, Arun

    2016-07-01

    Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be life-saving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae. PMID:27106239

  20. Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment.

    PubMed

    Nason, Martha C; Patel, Eshan U; Kirkpatrick, Allison R; Prodger, Jessica L; Shahabi, Kamnoosh; Tobian, Aaron A R; Gianella, Sara; Kalibbala, Sarah; Ssebbowa, Paschal; Kaul, Rupert; Gray, Ronald H; Quinn, Thomas C; Serwadda, David; Reynolds, Steven J; Redd, Andrew D

    2016-03-01

    Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation. PMID:27191006

  1. Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment.

    PubMed

    Nason, Martha C; Patel, Eshan U; Kirkpatrick, Allison R; Prodger, Jessica L; Shahabi, Kamnoosh; Tobian, Aaron A R; Gianella, Sara; Kalibbala, Sarah; Ssebbowa, Paschal; Kaul, Rupert; Gray, Ronald H; Quinn, Thomas C; Serwadda, David; Reynolds, Steven J; Redd, Andrew D

    2016-03-01

    Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation.

  2. Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment

    PubMed Central

    Nason, Martha C.; Patel, Eshan U.; Kirkpatrick, Allison R.; Prodger, Jessica L.; Shahabi, Kamnoosh; Tobian, Aaron A. R.; Gianella, Sara; Kalibbala, Sarah; Ssebbowa, Paschal; Kaul, Rupert; Gray, Ronald H.; Quinn, Thomas C.; Serwadda, David; Reynolds, Steven J.; Redd, Andrew D.

    2016-01-01

    Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation. PMID:27191006

  3. Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

    PubMed Central

    Vadlapudi, Aswani D.; Vadlapatla, Ramya K.; Mitra, Ashim K.

    2015-01-01

    Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections. PMID:23331181

  4. An extended study of seroprevalence of anti-Anisakis simplex IgE antibodies in Norwegian blood donors.

    PubMed

    Lin, A H; Nepstad, I; Florvaag, E; Egaas, E; Van Do, T

    2014-01-01

    During the last decade, cases of the fish parasite Anisakis simplex infection and allergy in human have increased in countries with high fish consumption. Our aim was to perform an extended seroprevalence study of anti-IgE antibodies against this parasite in Norway, one of the high fish-consuming countries. At the Department of Immunology and Transfusion Medicine and the Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway, two main groups of anonymized serum samples were collected; the first (n = 993) from recently recruited blood donors (designated 'BDO') and the second (n = 414) from patient with total IgE levels ≥1000 kU/l (designated 'IGE+'). The sera were analysed by the ImmunoCAP(®) method for total IgE and IgE antibodies against A. simplex, house dust mite (HDM), shrimp, cod, crab, brine shrimp and shrimp tropomyosin. The A. simplex positive sera were further tested by an enzyme-linked immunosorbent assay (ELISA) method, which uses 2 recombinant (r) major allergens, rAni s 1 and rAni s 7 as target antigens. SDS-PAGE and Western immunoblotting analyses were also performed. Whereas the prevalences by ImmunoCAP(®) were 0.4% and 16.2% in the BDO and IGE+ groups, respectively, analyses with recombinant allergens showed only 0.0% and 0.2%. Cross-reactivity and immunoblotting analyses suggested that most of the ImmunoCAP(®) positive sera were probably false-positive due to cross-sensitization to shrimp and HDM. However, positivity due to other A. simplex antigens should also be considered. Compared with other high fish-consuming countries, we observed a very low seroprevalence of anti-Anisakis IgE antibodies in a Norwegian population. PMID:24219706

  5. The function of herpes simplex virus genes: a primer for genetic engineering of novel vectors.

    PubMed Central

    Roizman, B

    1996-01-01

    Herpes simplex virus vectors are being developed for delivery and expression of human genes to the central nervous system, selective destruction of cancer cells, and as carriers for genes encoding antigens that induce protective immunity against infectious agents. Vectors constructed to meet these objectives must differ from wild-type virus with respect to host range, reactivation from latency, and expression of viral genes. The vectors currently being developed are (i) helper free amplicons, (ii) replication defective viruses, and (iii) genetically engineered replication competent viruses with restricted host range. Whereas the former two types of vectors require stable, continuous cell lines expressing viral genes for their replication, the replication competent viruses will replicate on approved primary human cell strains. PMID:8876131

  6. Tin Oxide Nanowires Suppress Herpes Simplex Virus-1 Entry and Cell-to-Cell Membrane Fusion

    PubMed Central

    Paulowicz, Ingo; Mishra, Yogendra K.; Adelung, Rainer; Shukla, Deepak

    2012-01-01

    The advent of nanotechnology has ushered in the use of modified nanoparticles as potential antiviral agents against diseases such as herpes simplex virus 1 and 2 (HSV-1) (HSV-2), human immunodeficiency virus (HIV), monkeypox virus, and hepatitis B virus. Here we describe the application of tin oxide (SnO2) nanowires as an effective treatment against HSV-1 infection. SnO2 nanowires work as a carrier of negatively charged structures that compete with HSV-1 attachment to cell bound heparan sulfate (HS), therefore inhibiting entry and subsequent cell-to-cell spread. This promising new approach can be developed into a novel form of broad-spectrum antiviral therapy especially since HS has been shown to serve as a cellular co-receptor for a number of other viruses as well, including the respiratory syncytial virus, adeno-associated virus type 2, and human papilloma virus. PMID:23110193

  7. The Function of Herpes Simplex Virus Genes: A Primer for Genetic Engineering of Novel Vectors

    NASA Astrophysics Data System (ADS)

    Roizman, Bernard

    1996-10-01

    Herpes simplex virus vectors are being developed for delivery and expression of human genes to the central nervous system, selective destruction of cancer cells, and as carriers for genes encoding antigens that induce protective immunity against infectious agents. Vectors constructed to meet these objectives must differ from wild-type virus with respect to host range, reactivation from latency, and expression of viral genes. The vectors currently being developed are (i) helper free amplicons, (ii) replication defective viruses, and (iii) genetically engineered replication competent viruses with restricted host range. Whereas the former two types of vectors require stable, continuous cell lines expressing viral genes for their replication, the replication competent viruses will replicate on approved primary human cell strains.

  8. Enhanced viral production and virus-mediated mortality of bacterioplankton in a natural iron-fertilized bloom event above the Kerguelen Plateau

    NASA Astrophysics Data System (ADS)

    Malits, A.; Christaki, U.; Obernosterer, I.; Weinbauer, M. G.

    2014-12-01

    Above the Kerguelen Plateau in the Southern Ocean natural iron fertilization sustains a large phytoplankton bloom over 3 months during austral summer. During the KEOPS1 project (KErguelen Ocean and Plateau compared Study1) we sampled this phytoplankton bloom during its declining phase along with the surrounding high-nutrient-low-chlorophyll (HNLC) waters to study the effect of natural iron fertilization on the role of viruses in the microbial food web. Bacterial and viral abundances were 1.7 and 2.1 times, respectively, higher within the bloom than in HNLC waters. Viral production and virus-mediated mortality of bacterioplankton were 4.1 and 4.9 times, respectively, higher in the bloom, while the fraction of infected cells (FIC) and the fraction of lysogenic cells (FLC) showed no significant differences between environments. The present study suggests viruses to be more important for bacterial mortality within the bloom and dominate over grazing of heterotrophic nanoflagellates (HNFs) during the late bloom phase. As a consequence, at least at a late bloom stage, viral lysis shunts part of the photosynthetically fixed carbon in iron-fertilized regions into the dissolved organic matter (DOM) pool with potentially less particulate organic carbon transferred to larger members of the food web or exported.

  9. Effect of recombinant adeno-associated virus mediated transforming growth factor-beta1 on corneal allograft survival after high-risk penetrating keratoplasty.

    PubMed

    Zhou, Lianhong; Zhu, Xiangxiang; Tan, Jinquan; Wang, Jiong; Xing, Yiqiao

    2013-06-01

    Corneal transplantation is one of the most common and successful transplant surgeries performed around the world. However, the high-risk corneal transplantation remains a high level of corneal graft failure. Gene transfer of immunomodulatory molecules is considered as one potential strategy in preventing allograft rejection. It is worthy evaluating the effects of the immunemodulating agent on corneal allograft rejection. The purpose of this paper is to investigate the effects and mechanisms of recombinant adeno-associated virus mediated transforming growth factor-beta1 (rAAV-TGF-beta1) on corneal allograft survival using a high-risk rat model after penetrating keratoplasty (PKP). The mean survival time (MST) of corneal grafts was observed and immuno-histochemical staining of TGF-beta1 and Ox-62 was performed in the study. The MST showed significant prolongation in the rAAV-TGF-beta1 group compared to the allograft group. The rejection index (RI) at day 10 revealed was significantly greater in the allograft group than that of the other two groups. Besides the increase of TGF-beta1, the expression of Ox-62 decreasing in rAAV-TGF-beta1 transplanted recipients was detected after transplantation. In short, treatment with rAAV-TGF-beta1 prolongs corneal allograft survival and inhibits the Ox-62 expression in grafts after high-risk PKP.

  10. Enhanced viral production and virus-mediated mortality of bacterioplankton in a natural iron-fertilized bloom event above the Kerguelen Plateau

    NASA Astrophysics Data System (ADS)

    Malits, A.; Christaki, U.; Obernosterer, I.; Weinbauer, M. G.

    2014-07-01

    Above the Kerguelen Plateau in the Southern Ocean natural iron fertilization sustains a large phytoplankton bloom over three months during austral summer. During the KEOPS1 project (KErguelen Ocean and Plateau compared Study1) we sampled this phytoplankton bloom during its declining phase along with the surrounding HNLC waters to study the effect of natural iron fertilization on the role of viruses in the microbial food web. Bacterial and viral abundances were 1.7 and 2.1 times, respectively, higher within the bloom than in HNLC waters. Viral production and virus-mediated mortality of bacterioplankton was 4.1 and 4.9 times, respectively, higher in the bloom, while the fraction of infected cells (FIC) and the fraction of lysogenic cells (FLC) showed no significant differences between environments. The present study suggests viruses to be more important for bacterial mortality within the bloom and dominate over protozoan grazing during the late bloom phase. As a consequence, at least at a late bloom stage, viral lysis shunts part of the photosynthetically fixed carbon in iron-fertilized regions into the dissolved organic matter (DOM) pool with potentially less particulate organic carbon transfered to larger members of the food web or exported.

  11. Herpes Simplex Encephalitis of the Parietal Lobe: A Rare Presentation

    PubMed Central

    Tkachenko, Lara; Moisi, Marc; Rostad, Steven; Umeh, Randle; Zwillman, Michael E; Tubbs, R. Shane; Page, Jeni; Newell, David W.; Delashaw, Johnny B

    2016-01-01

    A 69-year-old female with a history of breast cancer and hypertension presented with a rare case of herpes simplex encephalitis (HSE) isolated to her left parietal lobe. The patient’s first biopsy was negative for herpes simplex virus (HSV) I/II antigens, but less than two weeks later, the patient tested positive on repeat biopsy. This initial failure to detect the virus and the similarities between HSE and symptoms of intracranial hemorrhage (ICH) suggests repeat testing for HSV in the presence of ICH. Due to the frequency of patients with extra temporal HSE, a diagnosis of HSE should be more readily considered, particularly when a patient may not be improving and a concrete diagnosis has not been solidified. PMID:27774355

  12. Burning mouth syndrome due to herpes simplex virus type 1.

    PubMed

    Nagel, Maria A; Choe, Alexander; Traktinskiy, Igor; Gilden, Don

    2015-01-01

    Burning mouth syndrome is characterised by chronic orofacial burning pain. No dental or medical cause has been found. We present a case of burning mouth syndrome of 6 months duration in a healthy 65-year-old woman, which was associated with high copy numbers of herpes simplex virus type 1 (HSV-1) DNA in the saliva. Her pain resolved completely after antiviral treatment with a corresponding absence of salivary HSV-1 DNA 4 weeks and 6 months later. PMID:25833911

  13. Herpes simplex virus bronchiolitis in a cannabis user

    PubMed Central

    Libraty, Daniel H.; Bocelli, Lisa; Fraire, Armando

    2013-01-01

    Herpes simplex virus (HSV) lower respiratory tract infections in adults are uncommon. We present a case of HSV bronchiolitis and pneumonitis in an immunocompetent individual, likely linked to chronic habitual marijuana use and a herpetic orolabial ulcer. The case serves as a reminder to consider HSV as a potential unusual cause of lower respiratory tract infection/inflammation in individuals with chronic habitual marijuana use. PMID:26912481

  14. The Broader Autism Phenotype in Simplex and Multiplex Families

    ERIC Educational Resources Information Center

    Gerdts, Jennifer A.; Bernier, Raphael; Dawson, Geraldine; Estes, Annette

    2013-01-01

    Mothers, fathers, and siblings from 87 multiplex (M-mothers, M-fathers, and M-siblings) and 41 simplex (S-mothers, S-fathers, and S-siblings) Autism spectrum disorder families were assessed using the Broader Phenotype Autism Symptom Scale. S-mothers, S-fathers, and S-siblings showed more social interest and were more expressive in their use of…

  15. MOTIVATION INTERNALIZATION AND SIMPLEX STRUCTURE IN SELF-DETERMINATION THEORY.

    PubMed

    Ünlü, Ali; Dettweiler, Ulrich

    2015-12-01

    Self-determination theory, as proposed by Deci and Ryan, postulated different types of motivation regulation. As to the introjected and identified regulation of extrinsic motivation, their internalizations were described as "somewhat external" and "somewhat internal" and remained undetermined in the theory. This paper introduces a constrained regression analysis that allows these vaguely expressed motivations to be estimated in an "optimal" manner, in any given empirical context. The approach was even generalized and applied for simplex structure analysis in self-determination theory. The technique was exemplified with an empirical study comparing science teaching in a classical school class versus an expeditionary outdoor program. Based on a sample of 84 German pupils (43 girls, 41 boys, 10 to 12 years old), data were collected using the German version of the Academic Self-Regulation Questionnaire. The science-teaching format was seen to not influence the pupils' internalization of identified regulation. The internalization of introjected regulation differed and shifted more toward the external pole in the outdoor teaching format. The quantification approach supported the simplex structure of self-determination theory, whereas correlations may disconfirm the simplex structure. PMID:26595290

  16. Isolation of herpes simplex viruses by chick embryo culture.

    PubMed

    Akter, T; Tabassum, S; Jahan, M; Nessa, A; Islam, M N; Giasuddin, M

    2013-04-01

    The chick embryo is a versatile host system in diagnostic virology, especially for isolation of herpes simplex viruses. In this study, samples obtained from 57 clinically diagnosed patients with active herpetic lesions (35 genital & 22 non-genital) were cultured by chick embryo method for isolation of herpes simplex virus. After inoculation onto the chorioallantoic membrane (CAM) of 10-11 days old chick embryo, typical CAM reactions (pocks) appeared in 23(40.3%) samples after 3 days. CAM reactions were identified and typed by direct fluorescence antibody test and 22(95.6%) of 23 isolates gave positive results. Of this, 9(40.9%) were HSV-1 & 13(59.1%) were HSV-2. HSV-1 was isolated from 8(36.4%) of non-genital samples and from 1(7.1%) genital sample. HSV-2 was isolated from 13(92.8%) of genital samples, but none were isolated from non-genital samples. High isolation rate was obtained from vesicular stage of both non-genital (71.5%) and genital (57.1%) samples and from early lesions (sampled within 72 hours) of non-genital (50%) and genital (52.9%) specimen. The chorioallantoic membrane of chick embryo it is a simple, cheap and efficient method of cultivation of some viruses, including HSV. Thus, in settings where cell culture facilities are not available, it can be used for the isolation of herpes simplex viruses from clinical samples.

  17. Analysis of cortical shape in children with simplex autism.

    PubMed

    Dierker, Donna L; Feczko, Eric; Pruett, John R; Petersen, Steven E; Schlaggar, Bradley L; Constantino, John N; Harwell, John W; Coalson, Timothy S; Van Essen, David C

    2015-04-01

    We used surface-based morphometry to test for differences in cortical shape between children with simplex autism (n = 34, mean age 11.4 years) and typical children (n = 32, mean age 11.3 years). This entailed testing for group differences in sulcal depth and in 3D coordinates after registering cortical midthickness surfaces to an atlas target using 2 independent registration methods. We identified bilateral differences in sulcal depth in restricted portions of the anterior-insula and frontal-operculum (aI/fO) and in the temporoparietal junction (TPJ). The aI/fO depth differences are associated with and likely to be caused by a shape difference in the inferior frontal gyrus in children with simplex autism. Comparisons of average midthickness surfaces of children with simplex autism and those of typical children suggest that the significant sulcal depth differences represent local peaks in a larger pattern of regional differences that are below statistical significance when using coordinate-based analysis methods. Cortical regions that are statistically significant before correction for multiple measures are peaks of more extended, albeit subtle regional differences that may guide hypothesis generation for studies using other imaging modalities.

  18. MOTIVATION INTERNALIZATION AND SIMPLEX STRUCTURE IN SELF-DETERMINATION THEORY.

    PubMed

    Ünlü, Ali; Dettweiler, Ulrich

    2015-12-01

    Self-determination theory, as proposed by Deci and Ryan, postulated different types of motivation regulation. As to the introjected and identified regulation of extrinsic motivation, their internalizations were described as "somewhat external" and "somewhat internal" and remained undetermined in the theory. This paper introduces a constrained regression analysis that allows these vaguely expressed motivations to be estimated in an "optimal" manner, in any given empirical context. The approach was even generalized and applied for simplex structure analysis in self-determination theory. The technique was exemplified with an empirical study comparing science teaching in a classical school class versus an expeditionary outdoor program. Based on a sample of 84 German pupils (43 girls, 41 boys, 10 to 12 years old), data were collected using the German version of the Academic Self-Regulation Questionnaire. The science-teaching format was seen to not influence the pupils' internalization of identified regulation. The internalization of introjected regulation differed and shifted more toward the external pole in the outdoor teaching format. The quantification approach supported the simplex structure of self-determination theory, whereas correlations may disconfirm the simplex structure.

  19. Reactivation of herpes simplex virus-1 following epilepsy surgery☆

    PubMed Central

    de Almeida, Sérgio Monteiro; Crippa, Ana; Cruz, Cristina; de Paola, Luciano; de Souza, Luciana Paula; Noronha, Lucia; Torres, Luis Fernando Bleggi; Koneski, Julio A.S.; Pessa, Luis Felipe Cavalli; Nogueira, Meri Bordignon; Raboni, Sonia Mara; Silvado, Carlos Eduardo; Vidal, Luine Rosele

    2015-01-01

    Purpose The present study reports a case of encephalitis due to herpes simplex virus-1 (HSV-1), following surgical manipulation of the site of a primary infection. Methods Herpes simplex virus-1 infection was confirmed by CSF PCR and DNA sequencing. Results The patient was an 11-year-old girl who required temporal lobe surgery for epilepsy. She had meningoencephalitis due to HSV at the age of 20 months, and she was treated with acyclovir. Three years later, the patient developed uncontrolled seizures that became more frequent and changed in character at 11 years of age. On the 12th postoperative day, she developed fever and seizures, and she was diagnosed with HSV-1 by positive CSF PCR. She was treated with acyclovir (30 mg/kg/day for 21 days). In this report, we describe the patient and review the relevant literature. Conclusion The authors stress the potential risk of reactivation of HSV encephalitis after intracranial surgery. Herpes simplex virus encephalitis must be considered in neurosurgical patients who develop postoperative seizures and fever. PMID:26543809

  20. Herpes simplex virus: isolation, cytopathological characterization and antiviral sensitivity*

    PubMed Central

    Nozawa, Carlos; Hattori, Lilian Yumi; Galhardi, Ligia Carla Faccin; Lopes, Nayara; Bomfim, Wesley Andrade; de Cândido, Ligyana Korki; de Azevedo, Elbens Marcos Minoreli; Gon, Airton dos Santos; Linhares, Rosa Elisa Carvalho

    2014-01-01

    BACKGROUND Herpes simplex virus (HSV) infection is an endemic disease and it is estimated that 6095% of the adult population are infected with symptoms that are usually self-limiting, though they can be serious, extensive and prolonged in immunocompromised individuals, highlighted by the emergence of drug-resistant strains. The study of the wild-type HSV strains based on the cytopathogenic features and its antiviral sensitivity are important in the establishment of an antivirogram for controlling the infection. OBJECTIVE This study sought to isolate and examine the cytopathological characteristics of circulating strains of the Herpes simplex virus, from clinical specimens and their sensitivity to commercially available antiherpesvirus drugs, acyclovir, phosphonophormic acid and trifluridine. METHODS Herpes simplex virus isolation, cytopathological features and antiviral sensitivity assays were performed in cell culture by tissue culture infectious dose or plaque forming unit assay. RESULTS From twenty-two clinical specimens, we isolated and adapted nine strains. Overall, the cytopathic effect was detected 24 h post-infection (p.i.) and the presence of syncytia was remarkable 48 h p.i., observed after cell staining. Out of eight isolates, four developed plaques of varying sizes. All the isolates were sensitive to acyclovir, phosphonophormic and trifluridine, with the percentage of virus inhibition (%VI) ranging from 49.7-100%. CONCLUSIONS The methodology for HSV isolation and characterization is a straightforward approach, but the drug sensitivity test, regarded as being of great practical importance, needs to be better understood. PMID:24937819

  1. MONSS: A multi-objective nonlinear simplex search approach

    NASA Astrophysics Data System (ADS)

    Zapotecas-Martínez, Saúl; Coello Coello, Carlos A.

    2016-01-01

    This article presents a novel methodology for dealing with continuous box-constrained multi-objective optimization problems (MOPs). The proposed algorithm adopts a nonlinear simplex search scheme in order to obtain multiple elements of the Pareto optimal set. The search is directed by a well-distributed set of weight vectors, each of which defines a scalarization problem that is solved by deforming a simplex according to the movements described by Nelder and Mead's method. Considering an MOP with n decision variables, the simplex is constructed using n+1 solutions which minimize different scalarization problems defined by n+1 neighbor weight vectors. All solutions found in the search are used to update a set of solutions considered to be the minima for each separate problem. In this way, the proposed algorithm collectively obtains multiple trade-offs among the different conflicting objectives, while maintaining a proper representation of the Pareto optimal front. In this article, it is shown that a well-designed strategy using just mathematical programming techniques can be competitive with respect to the state-of-the-art multi-objective evolutionary algorithms against which it was compared.

  2. Rescue of skeletal muscles of gamma-sarcoglycan-deficient mice with adeno-associated virus-mediated gene transfer.

    PubMed

    Cordier, L; Hack, A A; Scott, M O; Barton-Davis, E R; Gao, G; Wilson, J M; McNally, E M; Sweeney, H L

    2000-02-01

    In humans, a subset of cases of Limb-girdle muscular dystrophy (LGMD) arise from mutations in the genes encoding one of the sarcoglycan (alpha, beta, gamma, or delta) subunits of the dystrophin-glycoprotein complex. While adeno-associated virus (AAV) is a potential gene therapy vector for these dystrophies, it is unclear if AAV can be used if a diseased muscle is undergoing rapid degeneration and necrosis. The skeletal muscles of mice lacking gamma-sarcoglycan (gsg-/- mice) differ from the animal models that have been evaluated to date in that the severity of the skeletal muscle pathology is much greater and more representative of that of humans with muscular dystrophy. Following direct muscle injection of a recombinant AAV [in which human gamma-sarcoglycan expression is driven by a truncated muscle creatine kinase (MCK) promoter/enhancer], we observed significant numbers of muscle fibers expressing gamma-sarcoglycan and an overall improvement of the histologic pattern of dystrophy. However, these results could be achieved only if injections into the muscle were prior to the development of significant fibrosis in the muscle. The results presented in this report show promise for AAV gene therapy for LGMD, but underscore the need for intervention early in the time course of the disease process.

  3. Herpes Simplex [corrected] Virus Type 2 Shedding From Male Circumcision Wounds in Rakai, Uganda.

    PubMed

    Grabowski, Mary K; Kigozi, Godfrey; Gray, Ronald H; Armour, Benjamin; Manucci, Jordyn; Serwadda, David; Redd, Andrew D; Nalugoda, Fred; Patel, Eshan U; Wawer, Maria J; Quinn, Thomas C; Tobian, Aaron A R

    2015-11-15

    A prospective observational study of 176 men coinfected with human immunodeficiency virus and herpes simplex virus type 2 (HSV-2) was conducted to assess whether their sexual partners may be at an increased risk of HSV-2 from male circumcision (MC) wounds. Preoperative and weekly penile lavage samples were tested for penile HSV-2 shedding. Prevalence risk ratios (PRRs) were estimated using Poisson regression. Detectable penile HSV-2 shedding was present in 9.7% of men (17 of 176) before MC, compared with 12.9% (22 of 170) at 1 week (PRR, 1.33; 95% confidence interval [CI], .74-2.38) and 14.8% (23 of 155) at 2 weeks (PRR, 1.50; 95% CI, .86-2.62) after MC. HSV-2 shedding was lower among men with healed MC wounds (adjusted PRR, 0.62; 95% CI, .35-1.08). Men undergoing MC should be counseled on sexual abstinence and condom use.

  4. Understanding natural herpes simplex virus immunity to inform next-generation vaccine design

    PubMed Central

    Sandgren, Kerrie J; Bertram, Kirstie; Cunningham, Anthony L

    2016-01-01

    Incremental advances in our knowledge of how natural immune control of herpes simplex virus (HSV) develops have yielded insight as to why previous vaccine attempts have only been partially successful, however, our understanding of these pathways, particularly in humans, is still incomplete. Further elucidation of the innate immune events that are responsible for stimulating these effector responses is required to accurately inform vaccine design. An enhanced understanding of the mechanism of action of novel adjuvants will also facilitate the rational choice of adjuvant to optimise such responses. Here we review the reasons for the hitherto partial HSV vaccine success and align these with our current knowledge of how natural HSV immunity develops. In particular, we focus on the innate immune response and the role of dendritic cells in inducing protective T-cell responses and how these pathways might be recapitulated in a vaccine setting. PMID:27525067

  5. Rapid diagnosis and quantification of herpes simplex virus with a green fluorescent protein reporter system.

    PubMed

    Kung, S H; Wang, Y C; Lin, C H; Kuo, R L; Liu, W T

    2000-11-01

    A genetically modified cell line (Vero-ICP10-EGFP) was constructed for detection of herpes simplex virus (HSV) by a simple, rapid and direct method. The cell line was developed by stable transfection of Vero cell with a plasmid encoding the green fluorescent protein (GFP) driven by the promoter of the HSV-2 ICP10 gene. As early as 6 h after infection with HSV, fluorescence-emitting cells can be observed under a fluorescence microscope. A single infected cell emitting fluorescence can be observed with soft agar overlay by inverted fluorescence microscopy. No induction of detectable fluorescence was seen following infections with human cytomegalovirus (HCMV), varicella zoster virus (VZV), coxsackievirus A16 and enterovirus 71. Analysis by flow cytometry also demonstrated that intensity of the triggered fluorescence is proportional to the titer of HSV inoculated. Taken together, this novel GFP reporter system could become a useful means for rapid detection and quantification of HSV in clinical specimens.

  6. Activity of tea tree (Melaleuca alternifolia) essential oil against L3 larvae of Anisakis simplex.

    PubMed

    Gómez-Rincón, Carlota; Langa, Elisa; Murillo, Paula; Valero, Marta Sofía; Berzosa, César; López, Víctor

    2014-01-01

    Nematicidal activity of Melaleuca alternifolia essential oil, commonly known as tea tree oil (TTO), was assayed in vitro against L3 larvae of Anisakis simplex. The results showed a mortality of 100% for concentrations between 7 and 10 μL/mL after 48 h of incubation, obtaining an LD50 value of 4.53 μL/mL after 24 hours and 4.27 μL/mL after 48 hours. Concentration-dependent inhibition of acetylcholinesterase was observed for tea tree essential oil showing inhibition values of 100% at 100 μL/mL. This fact suggests that TTO may act as an AChE inhibitor. Terpinen-4-ol was discarded as main larvicide compound as it did not show larvicidal or anticholinesterase activity. The data obtained suggest that the essential oil of Melaleuca alternifolia may have a great therapeutic potential for the treatment of human anisakiasis.

  7. The effect of cyclin-dependent kinases inhibitor treatment on experimental herpes simplex encephalitis mice.

    PubMed

    Zhou, Yu; Zeng, Yan-Ping; Zhou, Qin; Guan, Jing-Xia; Lu, Zu-Neng

    2016-08-01

    Herpes simplex encephalitis(HSE) is the most common and serious viral encephalitis in humans. There is a lack of effective medication to date for HSE. A better understanding of the mediators of tissue damage is essential for finding new targets for therapeutic intervention. In this project, we explored the effect of cyclin-dependent kinases inhibitor olomoucine treatment on experimental HSE mice. The following results were obtained: (1) olomoucine increased survival in HSE mice; (2) olomoucine inhibited microglial activation and reduced HSV-1-induced cytokines release; (3) olomoucine prevented neural cells apoptosis and attenuated brain tissue pathological changes following HSV-1 infection; (4) olomoucine reduced brain edema and improved neurological function in HSE. Overall, olomoucine can induce a blunted inflammatory response, maintain the blood vessel wall intact, improve neurological function and increase survival in HSE mice.

  8. Demonstration of Herpes Simplex Virus, Cytomegalovirus, and Epstein-Barr Virus in Colorectal Cancer

    PubMed Central

    Mehrabani-Khasraghi, Sahar; Ameli, Mitra; Khalily, Farzad

    2016-01-01

    Background: The present study sought to investigate molecular evidence for association between the presence of herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in CRC and colorectal polyp by using the PCR method in Iran. Methods: In this analytical case-control study, we selected 15 patients with CRC, 20 patients with colorectal polyp, and 35 patients without malignancy as controls. After DNA extraction, PCR was used to determine HSV, CMV, and EBV genome by specific primers. Statistical analysis was performed using χ2 tests. Results: Our findings demonstrated that there is no direct molecular evidence to support the association between HSV, CMV, and EBV and human colorectal malignancies. Conclusion: The results from this study do not exclude a possible oncogenic role of these viruses in neoplastic development of colon cells. PMID:26975327

  9. Latent acyclovir-resistant herpes simplex virus type 1 in trigeminal ganglia of immunocompetent individuals.

    PubMed

    van Velzen, Monique; van Loenen, Freek B; Meesters, Roland J W; de Graaf, Miranda; Remeijer, Lies; Luider, Theo M; Osterhaus, Albert D M E; Verjans, Georges M G M

    2012-05-15

    Specific mutations within the hypervariable herpes simplex virus (HSV) gene thymidine kinase (TK) gene lead to acyclovir (ACV) resistance. To uncover the existence of latent ACV-resistant (ACV(R)) HSV-1, we determined the genetic and functional variability of the HSV-1 TK gene pool in paired trigeminal ganglia (TG) of 5 immunocompetent individuals. The latent virus pool consisted of a donor-specific HSV-1 quasispecies, including one major ACV-sensitive (ACV(S)) and multiple phylogenetic-related minor ACV(S) and ACV(R) TK variants. Contrary to minor variants, major TK variants were shared between paired TG. The data demonstrate the coexistence of phylogenetic-related ACV(S) and ACV(R) latent HSV-1 in human TG.

  10. Activity of tea tree (Melaleuca alternifolia) essential oil against L3 larvae of Anisakis simplex.

    PubMed

    Gómez-Rincón, Carlota; Langa, Elisa; Murillo, Paula; Valero, Marta Sofía; Berzosa, César; López, Víctor

    2014-01-01

    Nematicidal activity of Melaleuca alternifolia essential oil, commonly known as tea tree oil (TTO), was assayed in vitro against L3 larvae of Anisakis simplex. The results showed a mortality of 100% for concentrations between 7 and 10 μL/mL after 48 h of incubation, obtaining an LD50 value of 4.53 μL/mL after 24 hours and 4.27 μL/mL after 48 hours. Concentration-dependent inhibition of acetylcholinesterase was observed for tea tree essential oil showing inhibition values of 100% at 100 μL/mL. This fact suggests that TTO may act as an AChE inhibitor. Terpinen-4-ol was discarded as main larvicide compound as it did not show larvicidal or anticholinesterase activity. The data obtained suggest that the essential oil of Melaleuca alternifolia may have a great therapeutic potential for the treatment of human anisakiasis. PMID:24967378

  11. Detection of antibodies to Anisakis simplex larvae by enzyme-linked immunosorbent assay and immunoelectrophoresis using crude or purified antigens.

    PubMed

    Gutierrez Ramos, R; Tsuji, M

    1994-12-01

    The enzyme-linked immunosorbent assay (ELISA) and immunoelectrophoresis (IEP) were used for the serodiagnosis of larval Anisakis simplex infections in man and immunized rabbits. Sephacryl S-300 gel filtration was used for separating crude antigen. Four fractions were obtained. Sera from patients with other helminth infections sometimes cross reacted with Anisakis larval antigens. With IEP, crude antigen is more sensitive than purified antigens. With ELISA, the third fraction is the most sensitive for detecting antibodies to Anisakis larvae in the sera of humans and immunized rabbits.

  12. Down-RANKing the Threat of HSV-1: RANKL Upregulates MHC-Class-I-Restricted Anti-Viral Immunity in Herpes Simplex Virus Infection.

    PubMed

    Finsterbusch, Katja; Piguet, Vincent

    2015-11-01

    Herpes simplex virus (HSV-1) is a major cause of viral skin infection in humans. Klenner and colleagues now show that the epidermal receptor activator of NFκB ligand (RANKL) is critical for the induction of anti-viral CD8(+) effector T cells (CTL) during cutaneous HSV-1 infection. Activation via RANKL prevents Langerhans cell apoptosis, thus leading to enhanced antigen transport to regional lymph nodes, increasing the CTL-priming capacity of lymph node dendritic cells.

  13. Down-RANKing the Threat of HSV-1: RANKL Upregulates MHC-Class-I-Restricted Anti-Viral Immunity in Herpes Simplex Virus Infection.

    PubMed

    Finsterbusch, Katja; Piguet, Vincent

    2015-11-01

    Herpes simplex virus (HSV-1) is a major cause of viral skin infection in humans. Klenner and colleagues now show that the epidermal receptor activator of NFκB ligand (RANKL) is critical for the induction of anti-viral CD8(+) effector T cells (CTL) during cutaneous HSV-1 infection. Activation via RANKL prevents Langerhans cell apoptosis, thus leading to enhanced antigen transport to regional lymph nodes, increasing the CTL-priming capacity of lymph node dendritic cells. PMID:26548487

  14. Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous: Diplotaxis simplex.

    PubMed

    Jdir, Hamida; Khemakham, Bassem; Najjaa, Hanen; Chakroun, Mouna; Jridi, Mourad; Ben Arfa, Abdelkarim; Ben Ali, Yassine; Zouari, Nacim

    2016-10-01

    Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae). Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers. Materials and methods The anti-proliferative activity of the extracts (10-70 μg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5-7.5 mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200 mg/kg) or indomethacin (50 mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods. Results Flower extracts contained a high level of polyphenolics (17.10-52.70 mg GAE/g) and flavonoids (74.20-100.60 mg QE/g), which correlate with its appreciable antioxidant potential in β-carotene peroxidation (IC50 value: 12.50-27.10 μg/mL), DPPH(•) radical-scavenging (IC50 value: 0.20-0.40 mg/mL), Fe(3+ )reducing (EC50 value: 0.10-0.14 mg/mL) and Fe(2+ )chelating (IC50 value: 0.20-0.60 mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC50 value: 62.0-63.25 μg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC50 value: 2.97 mg/mL) and reduced the paw oedema in mice (from 0.38 ± 0.01 to 0.24 ± 0.01 cm), 4 h post-carrageenan challenge. Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer. PMID:26916801

  15. Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk

    PubMed Central

    Wagner, Stefan; Thresher, Rosemary; Bland, Ross; Laible, Götz

    2015-01-01

    Biopharming for the production of recombinant pharmaceutical proteins in the mammary gland of transgenic animals is an attractive but laborious alternative compared to mammalian cell fermentation. The disadvantage of the lengthy process of genetically modifying an entire animal could be circumvented with somatic transduction of only the mammary epithelium with recombinant, replication-defective viruses. While other viral vectors offer very limited scope for this approach, vectors based on adeno-associated virus (AAV) appear to be ideal candidates because AAV is helper-dependent, does not induce a strong immune response and has no association with disease. Here, we sought to test the suitability of recombinant AAV (rAAV) for biopharming. Using reporter genes, we showed that injected rAAV efficiently transduced mouse mammary cells. When rAAV encoding human myelin basic protein (hMBP) was injected into the mammary glands of mice and rabbits, this resulted in the expression of readily detectable protein levels of up to 0.5 g/L in the milk. Furthermore we demonstrated that production of hMBP persisted over extended periods and that protein expression could be renewed in a subsequent lactation by re-injection of rAAV into a previously injected mouse gland. PMID:26463440

  16. Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk.

    PubMed

    Wagner, Stefan; Thresher, Rosemary; Bland, Ross; Laible, Götz

    2015-01-01

    Biopharming for the production of recombinant pharmaceutical proteins in the mammary gland of transgenic animals is an attractive but laborious alternative compared to mammalian cell fermentation. The disadvantage of the lengthy process of genetically modifying an entire animal could be circumvented with somatic transduction of only the mammary epithelium with recombinant, replication-defective viruses. While other viral vectors offer very limited scope for this approach, vectors based on adeno-associated virus (AAV) appear to be ideal candidates because AAV is helper-dependent, does not induce a strong immune response and has no association with disease. Here, we sought to test the suitability of recombinant AAV (rAAV) for biopharming. Using reporter genes, we showed that injected rAAV efficiently transduced mouse mammary cells. When rAAV encoding human myelin basic protein (hMBP) was injected into the mammary glands of mice and rabbits, this resulted in the expression of readily detectable protein levels of up to 0.5 g/L in the milk. Furthermore we demonstrated that production of hMBP persisted over extended periods and that protein expression could be renewed in a subsequent lactation by re-injection of rAAV into a previously injected mouse gland. PMID:26463440

  17. Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk.

    PubMed

    Wagner, Stefan; Thresher, Rosemary; Bland, Ross; Laible, Götz

    2015-10-14

    Biopharming for the production of recombinant pharmaceutical proteins in the mammary gland of transgenic animals is an attractive but laborious alternative compared to mammalian cell fermentation. The disadvantage of the lengthy process of genetically modifying an entire animal could be circumvented with somatic transduction of only the mammary epithelium with recombinant, replication-defective viruses. While other viral vectors offer very limited scope for this approach, vectors based on adeno-associated virus (AAV) appear to be ideal candidates because AAV is helper-dependent, does not induce a strong immune response and has no association with disease. Here, we sought to test the suitability of recombinant AAV (rAAV) for biopharming. Using reporter genes, we showed that injected rAAV efficiently transduced mouse mammary cells. When rAAV encoding human myelin basic protein (hMBP) was injected into the mammary glands of mice and rabbits, this resulted in the expression of readily detectable protein levels of up to 0.5 g/L in the milk. Furthermore we demonstrated that production of hMBP persisted over extended periods and that protein expression could be renewed in a subsequent lactation by re-injection of rAAV into a previously injected mouse gland.

  18. Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome.

    PubMed

    Daily, Jennifer L; Nash, Kevin; Jinwal, Umesh; Golde, Todd; Rogers, Justin; Peters, Melinda M; Burdine, Rebecca D; Dickey, Chad; Banko, Jessica L; Weeber, Edwin J

    2011-01-01

    Angelman syndrome (AS), a genetic disorder occurring in approximately one in every 15,000 births, is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. However, we have determined that abnormal calcium/calmodulin-dependent protein kinase II (CaMKII) regulation is seen in the maternal UBE3A deletion AS mouse model and is responsible for the major phenotypes. Specifically, there is an increased αCaMKII phosphorylation at the autophosphorylation sites Thr(286) and Thr(305/306), resulting in an overall decrease in CaMKII activity. CaMKII is not produced until after birth, indicating that the deficits associated with AS are not the result of developmental abnormalities. The present studies are focused on exploring the potential to rescue the learning and memory deficits in the adult AS mouse model through the use of an adeno-associated virus (AAV) vector to increase neuronal UBE3A expression. These studies show that increasing the levels of E6-AP in the brain using an exogenous vector can improve the cognitive deficits associated with AS. Specifically, the associative learning deficit was ameliorated in the treated AS mice compared to the control AS mice, indicating that therapeutic intervention may be possible in older AS patients.

  19. Adeno-associated virus-mediated expression of apolipoprotein (a) kringles suppresses hepatocellular carcinoma growth in mice.

    PubMed

    Lee, Kyuhyun; Yun, Sung-Tae; Kim, Young-Gun; Yoon, Yeup; Jo, Eui-Cheol

    2006-05-01

    Hepatocellular carcinoma (HCC) constitutes more than 90% of all primary liver cancers. HCC is a hypervascular tumor that develops from dedifferentiation of small avascular HCC and is therefore a good target for anti-angiogenic gene therapy. Recent studies have identified apolipoprotein(a) [apo(a)] kringles LK68 and LK8 (LKs) as having a potential antiangiogenic and anti-tumor activity, and the current study evaluates the therapeutic potential of gene therapy with recombinant adeno-associated virus carrying genes encoding LKs (rAAV-LK) in the treatment of hypervascular HCC. We generated rAAV-LK to obtain persistent transgene expression in vivo, which is essential for anti-angiogenic therapy. The rAAV-produced LKs substantially inhibited proliferation and migration of human umbilical vein endothelial cells (HUVECs) in vitro, validating their anti-angiogenic potential. Intramuscular administration of rAAV-LK gave 60% to 84% suppression (P < .05) of tumor growth in mice bearing subcutaneously transplanted HCC derived from Huh-7 and Hep3B cells, respectively. Histological and immunohistochemical analyses of HCC tumor sections showed that a single administration of rAAV-LK gave rise to persistent expression of LKs that inhibited tumor angiogenesis and triggered tumor apoptosis, and, thus, significantly suppressed tumor growth. The administration of rAAV-LK provided a significant survival benefit (P < .05), and 3 of 10 rAAV-LK-treated mice were still alive without visible tumors and without clinical symptoms 188 days after treatment. In conclusion, rAAV-LK is a potential candidate for anti-angiogenic gene therapy in the treatment of HCC.

  20. Adeno-Associated Virus-Mediated Correction of a Canine Model of Glycogen Storage Disease Type Ia

    PubMed Central

    Weinstein, David A.; Correia, Catherine E.; Conlon, Thomas; Specht, Andrew; Verstegen, John; Onclin-Verstegen, Karine; Campbell-Thompson, Martha; Dhaliwal, Gurmeet; Mirian, Layla; Cossette, Holly; Falk, Darin J.; Germain, Sean; Clement, Nathalie; Porvasnik, Stacy; Fiske, Laurie; Struck, Maggie; Ramirez, Harvey E.; Jordan, Juan; Andrutis, Karl; Chou, Janice Y.; Byrne, Barry J.

    2010-01-01

    Abstract Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-α. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver. PMID:20163245

  1. Epstein–Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation

    PubMed Central

    Hernando, Henar; Islam, Abul B. M. M. K.; Rodríguez-Ubreva, Javier; Forné, Ignasi; Ciudad, Laura; Imhof, Axel; Shannon-Lowe, Claire; Ballestar, Esteban

    2014-01-01

    Epstein–Barr virus (EBV) infects and transforms human primary B cells inducing indefinite proliferation. To investigate the potential participation of chromatin mechanisms during the EBV-mediated transformation of resting B cells we performed an analysis of global changes in histone modifications. We observed a remarkable decrease and redistribution of heterochromatin marks including H4K20me3, H3K27me3 and H3K9me3. Loss of H4K20me3 and H3K9me3 occurred at constitutive heterochromatin repeats. For H3K27me3 and H3K9me3, comparison of ChIP-seq data revealed a decrease in these marks in thousands of genes, including clusters of HOX and ZNF genes, respectively. Moreover, DNase-seq data comparison between resting and EBV-transformed B cells revealed increased endonuclease accessibility in thousands of genomic sites. We observed that both loss of H3K27me3 and increased accessibility are associated with transcriptional activation. These changes only occurred in B cells transformed with EBV and not in those stimulated to proliferate with CD40L/IL-4, despite their similarities in the cell pathways involved and proliferation rates. In fact, B cells infected with EBNA-2 deficient EBV, which have much lower proliferation rates, displayed similar decreases for heterochromatic histone marks. Our study describes a novel phenomenon related to transformation of B cells, and highlights its independence of the pure acquisition of proliferation. PMID:24097438

  2. JPLEX: Java Simplex Implementation with Branch-and-Bound Search for Automated Test Assembly

    ERIC Educational Resources Information Center

    Park, Ryoungsun; Kim, Jiseon; Dodd, Barbara G.; Chung, Hyewon

    2011-01-01

    JPLEX, short for Java simPLEX, is an automated test assembly (ATA) program. It is a mixed integer linear programming (MILP) solver written in Java. It reads in a configuration file, solves the minimization problem, and produces an output file for postprocessing. It implements the simplex algorithm to create a fully relaxed solution and…

  3. The Dynamics of HCF-1 Modulation of Herpes Simplex Virus Chromatin during Initiation of Infection

    PubMed Central

    Vogel, Jodi L.; Kristie, Thomas M.

    2013-01-01

    Successful infection of herpes simplex virus is dependent upon chromatin modulation by the cellular coactivator host cell factor-1 (HCF-1). This review focuses on the multiple chromatin modulation components associated with HCF-1 and the chromatin-related dynamics mediated by this coactivator that lead to the initiation of herpes simplex virus (HSV) immediate early gene expression. PMID:23698399

  4. High hydrostatic pressure treatment of finfish to inactivate Anisakis simplex.

    PubMed

    Dong, Faye M; Cook, Allison R; Herwig, Russell P

    2003-10-01

    High hydrostatic pressure has been demonstrated to be a useful technique for treating food to reduce the number of pathogenic organisms and to extend shelf life. Most research in this area has focused on bacteria. However, a concern in the sashimi (raw fish) industry is that nematode worms such as Anisakis simplex occur naturally in cold-water marine fish. The objectives of this research were to perform a pilot study to determine the effect of high hydrostatic pressure on the viability of Anisakis simplex larvae, commonly found in king salmon and arrowtooth flounder, and to evaluate the effects of high hydrostatic pressure on the color and texture of the fish fillets. Pieces of fish (ca. 100 g per bag) containing 13 to 118 larvae were exposed to pressures of up to 80,000 lb/in2 (552 MPa) for up to 180 s. The times and pressures required to kill 100% of the larvae were as follows: 30 to 60 s at 60,000 lb/in2 (414 MPa), 90 to 180 s at 40,000 lb/in2 (276 MPa), and 180 s at 30,000 lb/in2 (207 MPa). For all salmon treatments that killed 100% of the larvae, a significant increase in the whiteness of the flesh was observed. Although high hydrostatic pressure was effective in killing A. simplex larvae in raw fish fillets, its significant effect on the color and overall appearance of the fillet may limit its application to the processing of fish for raw-fish markets.

  5. Simplex GPS and InSAR Inversion Software

    NASA Technical Reports Server (NTRS)

    Donnellan, Andrea; Parker, Jay W.; Lyzenga, Gregory A.; Pierce, Marlon E.

    2012-01-01

    Changes in the shape of the Earth's surface can be routinely measured with precisions better than centimeters. Processes below the surface often drive these changes and as a result, investigators require models with inversion methods to characterize the sources. Simplex inverts any combination of GPS (global positioning system), UAVSAR (uninhabited aerial vehicle synthetic aperture radar), and InSAR (interferometric synthetic aperture radar) data simultaneously for elastic response from fault and fluid motions. It can be used to solve for multiple faults and parameters, all of which can be specified or allowed to vary. The software can be used to study long-term tectonic motions and the faults responsible for those motions, or can be used to invert for co-seismic slip from earthquakes. Solutions involving estimation of fault motion and changes in fluid reservoirs such as magma or water are possible. Any arbitrary number of faults or parameters can be considered. Simplex specifically solves for any of location, geometry, fault slip, and expansion/contraction of a single or multiple faults. It inverts GPS and InSAR data for elastic dislocations in a half-space. Slip parameters include strike slip, dip slip, and tensile dislocations. It includes a map interface for both setting up the models and viewing the results. Results, including faults, and observed, computed, and residual displacements, are output in text format, a map interface, and can be exported to KML. The software interfaces with the QuakeTables database allowing a user to select existing fault parameters or data. Simplex can be accessed through the QuakeSim portal graphical user interface or run from a UNIX command line.

  6. MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11

    PubMed Central

    Ashraf, Usama; Zhu, Bibo; Ye, Jing; Wan, Shengfeng; Nie, Yanru; Chen, Zheng; Cui, Min; Wang, Chong; Duan, Xiaodong; Zhang, Hao; Chen, Huanchun

    2016-01-01

    ABSTRACT Japanese encephalitis virus (JEV) can invade the central nervous system and consequently induce neuroinflammation, which is characterized by profound neuronal cell damage accompanied by astrogliosis and microgliosis. Albeit microRNAs (miRNAs) have emerged as major regulatory noncoding RNAs with profound effects on inflammatory response, it is unknown how astrocytic miRNAs regulate JEV-induced inflammation. Here, we found the involvement of miR-19b-3p in regulating the JEV-induced inflammatory response in vitro and in vivo. The data demonstrated that miR-19b-3p is upregulated in cultured cells and mouse brain tissues during JEV infection. Overexpression of miR-19b-3p led to increased production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and chemokine (C-C motif) ligand 5, after JEV infection, whereas knockdown of miR-19b-3p had completely opposite effects. Mechanistically, miR-19b-3p modulated the JEV-induced inflammatory response via targeting ring finger protein 11, a negative regulator of nuclear factor kappa B signaling. We also found that inhibition of ring finger protein 11 by miR-19b-3p resulted in accumulation of nuclear factor kappa B in the nucleus, which in turn led to higher production of inflammatory cytokines. In vivo silencing of miR-19b-3p by a specific antagomir reinvigorates the expression level of RNF11, which in turn reduces the production of inflammatory cytokines, abrogates gliosis and neuronal cell death, and eventually improves the survival rate in the mouse model. Collectively, our results demonstrate that miR-19b-3p positively regulates the JEV-induced inflammatory response. Thus, miR-19b-3p targeting may constitute a thought-provoking approach to rein in JEV-induced inflammation. IMPORTANCE Japanese encephalitis virus (JEV) is one of the major causes of acute encephalitis in humans worldwide. The pathological features of JEV-induced encephalitis are inflammatory reactions and

  7. Immunological study of the aqueous humor in ocular herpes simplex.

    PubMed

    Denis, J

    1976-01-01

    (1) Isolation of herpetic virus and immunological studies of the serum and aqueous humor are two complementary methods of investigation in the diagnosis of ocular herpes simplex infection, their relative value depending on the clinical situation. (2) Of the different immunological techniques that of antibody titration by the hemagglutination method is an easy, sensitive test, but only if the Goldmann-Witner ratio is calculated. By this technique, the diagnosis of herpetic infection can be made in unusual clinical presentations or old cases in which all specificity had disappeared.

  8. Manipulation of herpes simplex virus type 1 by dielectrophoresis.

    PubMed

    Hughes, M P; Morgan, H; Rixon, F J; Burt, J P; Pethig, R

    1998-09-16

    The frequency-dependent dielectrophoretic behaviour of an enveloped mammalian virus, herpes simplex virus type 1 is described. It is demonstrated that over the range 10 kHz-20 MHz, these viral particles, when suspended in an aqueous medium of conductivity 5 mS m(-1), can be manipulated by both positive and negative dielectrophoresis using microfabricated electrode arrays. The observed transition from positive to negative dielectrophoresis at frequencies around 4.5 MHz is in qualitative agreement with a simple model of the virus as a conducting particle surrounded by an insulating membrane.

  9. [Virus-induced anorectal diseases. Condylomata acuminata and herpes simplex].

    PubMed

    Wienert, V

    2004-03-01

    Genital warts (condylomata acuminata) are very common sexually transmitted infections which may be present in perianal, anal and rarely rectal sites. Their incidence in the population is about 0.1%. As a rule, the diagnosis is simple and can be made by inspection; some variants pose a diagnostic challenge. The therapy is not uniform; it must be adjusted to the clinical manifestations and can be conservative or operative. Herpes simplex infections are also common; they too may be transferred by sexual intercourse and then commonly appear in the perianal skin and the rectal mucosa. While the clinical diagnosis is often difficult, the treatment is simple and effective.

  10. Linearized dynamics from the 4-simplex Regge action

    SciTech Connect

    Dittrich, Bianca; Freidel, Laurent; Speziale, Simone

    2007-11-15

    We study the relation between the Hessian matrix of the Riemannian Regge action on a 4-simplex and linearized quantum gravity. We give an explicit formula for the Hessian as a function of the geometry, and show that it has a single zero mode. We then use a 3D lattice model to show that (i) the zero mode is a remnant of the continuum diffeomorphism invariance, and (ii) we recover the complete free graviton propagator in the continuum limit. The results help clarify the structure of the boundary state needed in the recent calculations of the graviton propagator in loop quantum gravity, and, in particular, its role in fixing the gauge.

  11. A Simplex-Like Algorithm for Fisher Markets

    NASA Astrophysics Data System (ADS)

    Adsul, Bharat; Babu, Ch. Sobhan; Garg, Jugal; Mehta, Ruta; Sohoni, Milind

    We propose a new convex optimization formulation for the Fisher market problem with linear utilities. Like the Eisenberg-Gale formulation, the set of feasible points is a polyhedral convex set while the cost function is non-linear; however, unlike that, the optimum is always attained at a vertex of this polytope. The convex cost function depends only on the initial endowments of the buyers. This formulation yields an easy simplex-like pivoting algorithm which is provably strongly polynomial for many special cases.

  12. Neonatal herpes simplex virus infection: epidemiology and treatment.

    PubMed

    James, Scott H; Kimberlin, David W

    2015-03-01

    Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are highly prevalent viruses capable of establishing lifelong infection. Genital herpes in women of childbearing age represents a major risk for mother-to-child transmission (MTCT) of HSV infection, with primary and first-episode genital HSV infections posing the highest risk. The advent of antiviral therapy with parenteral acyclovir has led to significant improvement in neonatal HSV disease mortality. Further studies are needed to improve the clinician's ability to identify infants at increased risk for HSV infection and prevent MTCT, and to develop novel antiviral agents with increased efficacy in infants with HSV infection.

  13. Unusual Initial Presentation of Herpes Simplex Virus as Inguinal Lymphadenopathy

    PubMed Central

    Fleming, Sarah A.; Strickler, John G.

    2015-01-01

    Genital herpes simplex virus (HSV) infections are a common cause of inguinal lymphadenopathy. However, surgical excision of enlarged inguinal nodes is almost never performed to initially diagnose genital herpes simplex virus, due to the distinct external presentation of genital herpetic vesicles that usually occur with the first symptoms of infection. Therefore, the histologic and immunophenotypic features of HSV-associated inguinal lymphadenopathy are unfamiliar to most pathologists. The current report describes the lymph node pathology of two immunocompetent patients, whose initial HSV diagnosis was established through surgical excision of enlarged inguinal lymph nodes. Histologic examination showed features consistent with viral lymphadenopathy, including florid follicular hyperplasia, monocytoid B-cell hyperplasia, and paracortical hyperplasia without extensive necrosis. Immunohistochemical stains for HSV antigens, using polyclonal anti-HSV I and II antibodies, demonstrate strong immunoreactivity for HSV in a small number of cells in the subcapsular sinuses, especially in areas with monocytoid B-cell hyperplasia. Rare scattered HSV-positive cells also are identified in paracortical areas and germinal centers. We conclude that an initial diagnosis of genital HSV infection may be established by inguinal lymph node biopsy. PMID:25815228

  14. Unusual initial presentation of herpes simplex virus as inguinal lymphadenopathy.

    PubMed

    Fleming, Sarah A; Strickler, John G

    2015-01-01

    Genital herpes simplex virus (HSV) infections are a common cause of inguinal lymphadenopathy. However, surgical excision of enlarged inguinal nodes is almost never performed to initially diagnose genital herpes simplex virus, due to the distinct external presentation of genital herpetic vesicles that usually occur with the first symptoms of infection. Therefore, the histologic and immunophenotypic features of HSV-associated inguinal lymphadenopathy are unfamiliar to most pathologists. The current report describes the lymph node pathology of two immunocompetent patients, whose initial HSV diagnosis was established through surgical excision of enlarged inguinal lymph nodes. Histologic examination showed features consistent with viral lymphadenopathy, including florid follicular hyperplasia, monocytoid B-cell hyperplasia, and paracortical hyperplasia without extensive necrosis. Immunohistochemical stains for HSV antigens, using polyclonal anti-HSV I and II antibodies, demonstrate strong immunoreactivity for HSV in a small number of cells in the subcapsular sinuses, especially in areas with monocytoid B-cell hyperplasia. Rare scattered HSV-positive cells also are identified in paracortical areas and germinal centers. We conclude that an initial diagnosis of genital HSV infection may be established by inguinal lymph node biopsy.

  15. Zebrafish as a new model for herpes simplex virus type 1 infection.

    PubMed

    Burgos, Javier S; Ripoll-Gomez, Jorge; Alfaro, Juan M; Sastre, Isabel; Valdivieso, Fernando

    2008-12-01

    The zebrafish (Danio rerio) is rapidly gaining ground as a disease model. However, until now, the use of this species with human pathogens has been restricted to just three bacteria; no studies involving viruses that infect humans are recorded. In this study, the zebrafish was used as a model of herpes simplex virus type 1 (HSV-1) infection of the nervous system. Fish infected using viral culture supernatants showed detectable HSV-1 DNA concentrations 1-4 days after inoculation, indicating that this virus can experimentally infect and persist in this host. The kinetics of infection was dose dependent, especially in the head. Histological immunodetection of HSV-1 glycoproteins confirmed the presence of HSV-1 in the organs studied; infection led to histopathological changes. Moreover, the suppression of the immune system by cyclophosphamide and the antiviral effect of acyclovir were demonstrated. The infection of the encephalon was studied in detail, and the time course of viral colonization recorded. Immunofluorescence studies provided immunoreactive evidence of viral antigens in the encephalon and spinal cord. Viruses cleared from infected brains showed the ability to infect human neuroblastoma cells. This study is the first to demonstrate HSV-1 infection in the zebrafish and manifests the potential use of this species in herpesvirus studies.

  16. Intracerebral propagation of Alzheimer's disease: strengthening evidence of a herpes simplex virus etiology

    PubMed Central

    Ball, Melvyn J.; Lukiw, Walter J.; Kammerman, Eli M.; Hill, James M.

    2012-01-01

    Background A faulty human protein, abnormally phosphorylated tau, was recently publicized to spread “like a virus” from neuron to neuron in Alzheimer patients' brains. For several decades, we have been amassing arguments showing that herpes simplex virus type 1 (HSV-1), not p-tau, propagates this inter-neuronal, trans-synaptic pathological cascade. Methods We reiterate convincing data from our own (and other) laboratories, reviewing the first anatomic foothold neurofibrillary tangles gain in brainstem and/or entorhinal cortex; the chronic immunosurveillance cellularity of the trigeminal ganglia wherein HSV-1 awakens from latency to reactivate; the inabilities of p-tau protein's physical properties to promote it to jump synapses; the amino-acid homology between human p-tau and VP22, a key target for phosphorylation by HSV serine/threonine-protein kinase UL13; and the exosomic secretion of HSV-1-infected cells' L-particles, attesting to the cell-to-cell passage of microRNAs of herpes viruses. Results The now-maturing construct that reactivated HSV-1 best accounts for the intracerebral propagation of AD changes in the human brain should at last seem highly attractive. This hypothesis might even explain statins' apparent mechanism in some studies for lowering AD incidence. Conclusion Provided that funding agencies will quickly ignite a new realm of investigation, the rejuvenated enthusiasm for testing this optimistic construct holds incalculable potential for rapid, efficacious clinical application, through already available and relatively safe anti-viral therapeutics. PMID:23159044

  17. Concomitant herpes simplex virus colitis and hepatitis in a man with ulcerative colitis

    PubMed Central

    Phadke, Varun K.; Friedman-Moraco, Rachel J.; Quigley, Brian C.; Farris, Alton B.; Norvell, J. P.

    2016-01-01

    Abstract Background: Herpesvirus infections often complicate the clinical course of patients with inflammatory bowel disease; however, invasive disease due to herpes simplex virus is distinctly uncommon. Methods: We present a case of herpes simplex virus colitis and hepatitis, review all the previously published cases of herpes simplex virus colitis, and discuss common clinical features and outcomes. We also discuss the epidemiology, clinical manifestations, diagnosis, and management of herpes simplex virus infections, focusing specifically on patients with inflammatory bowel disease. Results: A 43-year-old man with ulcerative colitis, previously controlled with an oral 5-aminosalicylic agent, developed symptoms of a colitis flare that did not respond to treatment with systemic corticosteroid therapy. One week later he developed orolabial ulcers and progressive hepatic dysfunction, with markedly elevated transaminases and coagulopathy. He underwent emergent total colectomy when imaging suggested bowel micro-perforation. Pathology from both the colon and liver was consistent with herpes simplex virus infection, and a viral culture of his orolabial lesions and a serum polymerase chain reaction assay also identified herpes simplex virus. He was treated with systemic antiviral therapy and made a complete recovery. Conclusions: Disseminated herpes simplex virus infection with concomitant involvement of the colon and liver has been reported only 3 times in the published literature, and to our knowledge this is the first such case in a patient with inflammatory bowel disease. The risk of invasive herpes simplex virus infections increases with some, but not all immunomodulatory therapies. Optimal management of herpes simplex virus in patients with inflammatory bowel disease includes targeted prophylactic therapy for patients with evidence of latent infection, and timely initiation of antiviral therapy for those patients suspected to have invasive disease. PMID:27759636

  18. Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infections

    SciTech Connect

    Straus, S.E. )

    1989-12-01

    The major features that distinguish recurrent herpes simplex virus infections from zoster are illustrated in this article by two case histories. The clinical and epidemiologic features that characterize recurrent herpes simplex virus and varicella-zoster virus infections are reviewed. It is noted that herpesvirus infections are more common and severe in patients with cellular immune deficiency. Each virus evokes both humoral and cellular immune response in the course of primary infection. DNA hybridization studies with RNA probes labelled with sulfur-35 indicate that herpes simplex viruses persist within neurons, and that varicella-zoster virus is found in the satellite cells that encircle the neurons.

  19. Limb hypoplasia resulting from intrauterine infection with herpes simplex virus: a case report.

    PubMed

    Carola, D; Skibo, M; Cannon, S; Cam, K M; Hyde, P; Aghai, Z H

    2014-11-01

    Intrauterine infection with herpes simplex virus, although very rare, has devastating effects on multiple organ systems in the fetus and can lead to in utero fetal demise. Neonates born following intrauterine herpes simplex virus infection commonly manifest with cutaneous lesions, ocular damage and/or brain abnormalities. We describe the case of a dichorionic, diamniotic twin gestation complicated by intrauterine herpes simplex virus infection. This infection led to the fetal demise of twin A and a very uncommon presentation of limb hypoplasia in twin B.

  20. Herpes simplex virus 2 meningitis: a retrospective cohort study.

    PubMed

    Miller, Stephanie; Mateen, Farrah J; Aksamit, Allen J

    2013-04-01

    Herpes simplex virus 2 is a leading cause of viral meningitis and the most commonly recognized infectious cause of benign, recurrent meningitis. We report a retrospective, observational cohort study of patients with herpes simplex virus type 2 (HSV-2) meningitis, confirmed by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). The terms "herpes simplex," "meningitis," or "encephalitis" were searched in the medical records system of the Mayo Clinic in Rochester, Minnesota (1995-2008). Patients were included if they had a clinical diagnosis of meningitis and HSV-2 detected by PCR in the CSF. There were 28 patients with 33 episodes identified (83 % female; mean age at presentation of meningitis 36 years, range 17-53; mean time to HSV2 detection from symptom onset 3 days, range 0-6; history of genital herpes 23 %). No patient took oral antiviral treatment at the time of presentation. Episodes were most likely to include headache (100 %), photophobia (47 %), self-reported fever (45 %), meningismus (44 %), and nausea and/or vomiting (29 %). CSF at the time of meningitis was notable for elevated protein (mean 156 g/dL, range 60-258) and white cell count (mean 504 cells/μL, range 86-1,860) with normal glucose (mean 54 mg/dL, range 32-80). Mollaret cells were never detected. Neuroimaging was most often normal (83 %) when performed, although some cases showed nonspecific (14 %) or meningeal changes (3 %). There was no consistent relationship to genital herpes. The duration of treatment with intravenous acyclovir ranged from 3 to 14 days for the first meningitic episode (daily dose range from 500 to 1,000 mg and total dose range from 500 mg q8h for 3 days to 800 mg q8h for 14 days). For subsequent episodes, the duration of treatment of intravenous acyclovir ranged from less than 1 to 14 days (total dose range from 1,390 mg for 1 day to 900 mg q8h for 10 days). The dose of valacyclovir ranged from 500 mg once daily to 500 mg four times daily. The median duration

  1. Haemoglobin, a new major allergen of Anisakis simplex.

    PubMed

    González-Fernández, Juan; Daschner, Alvaro; Nieuwenhuizen, Natalie E; Lopata, Andreas L; Frutos, Consolación De; Valls, Ana; Cuéllar, Carmen

    2015-05-01

    Gastro-allergic anisakiasis and Anisakis sensitisation associated chronic urticaria are diseases which differ in their IgE and IgG4 responses against both crude extract and specific allergens. Anisakis and Ascaris are closely related nematodes that usually cause problems with specificity in immunodiagnostics. In this study we measured IgE and IgG4 antibodies against Anisakis simplex sensu lato (s. l.) and Ascaris suum haemoglobins in sera of 21 gastro-allergic anisakiasis and 23 chronic urticaria patients. We used a capture ELISA with the anti-Anisakis haemoglobin monoclonal antibody 4E8g, which also recognises Ascaris haemoglobin. In addition, we determined specific IgE and IgG4 to both nematodes by indirect ELISA and immunoblotting. Anti-A. simplex s. l. haemoglobin IgE and IgG4 levels were higher in gastro-allergic anisakiasis than in chronic urticaria patients (P=0.002 and 0.026, respectively). Surprisingly, no patient had detectable IgE levels against A. suum haemoglobin. Finally, we carried out an in silico study of the B-cell epitopes of both haemoglobin molecules. Five epitopes were predicted in Anisakis pegreffii and four in A. suum haemoglobin. The epitope propensity values of Anisakis haemoglobin in the equivalent IgE binding region of the allergenic haemoglobin Chi t 1 from Chironomus thummi, were higher those of the Ascaris haemoglobin. In conclusion, we describe A. simplex haemoglobin as a new major allergen (Ani s 13), being recognised by a large number (64.3%) of sensitised patients and up to 80.9% in patients with gastro-allergic anisakiasis. The presence of a specific epitope and the different values of epitope propensity between Anisakis and Ascaris haemoglobin could explain the lack of cross-reactivity between the two molecules. The absence of IgE reactivity to Ascaris haemoglobin in Anisakis patients makes Anisakis haemoglobin (Ani s 13) a potential candidate for developing more specific diagnosis tools. PMID:25683373

  2. Comparison of the association with eczema herpeticum in the two predominant genotypes of herpes simplex virus type 1.

    PubMed

    Umene, K; Yoshida, M; Sakaoka, H

    1996-08-01

    Eczema herpeticum, sometimes called Kaposi's varicelliform eruption, is usually caused by a disseminated herpes simplex virus infection in a patient whose underlying skin disease in atopic dermatitis. Herpes simplex virus type 1 (HSV-1), a widespread infectious agent in human populations, is the etiologic agent of eczema herpeticum. Analyses of restriction fragment length polymorphism (RFLP) of HSV-1 strains isolated in Japan, using restriction endonucleases, revealed the presence of two predominant genotypes of F1 and F35. The number of HSV-1 strains of F1 genotype was over twice that of the F35 genotype, and the nucleotide change between F1 and F35 was estimated to be 1.5%. The question of whether the genomic difference between two predominant genotypes could influence clinical manifestations remained to be addressed. On the basis of RFLP, we determined genotypes of HSV-1 strains isolated from the patients in Japan, including those with eczema herpeticum. Two of four HSV-1 strains of F35 genotype were from patients with eczema herpeticum, whereas none of 12 HSV-1 strains of F1 genotype was from those with eczema herpeticum. Thus, the F35 genotype seemed to be associated more frequently with eczema herpeticum than the F1 genotype.

  3. The challenges and opportunities for the development of a T-cell epitope-based herpes simplex vaccine.

    PubMed

    Kuo, Tiffany; Wang, Christine; Badakhshan, Tina; Chilukuri, Sravya; BenMohamed, Lbachir

    2014-11-28

    Herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) infections have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a billion individuals worldwide. HSV-1 infections are predominant than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries, their development has been difficult. During the most recent National Institute of Health (NIH) workshop titled "Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities", basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One "common denominator" among previously failed clinical herpes vaccine trials is that they either used a whole virus or a whole viral protein, which contain both "pathogenic symptomatic" and "protective asymptomatic" antigens and epitopes. In this report, we continue to advocate developing "asymptomatic" epitope-based sub-unit vaccine strategies that selectively incorporate "protective asymptomatic" epitopes which: (i) are exclusively recognized by effector memory CD4(+) and CD8(+) T cells (TEM cells) from "naturally" protected seropositive asymptomatic individuals; and (ii) protect human leukocyte antigen (HLA) transgenic animal models of ocular and genital herpes. We review the role of animal models in herpes vaccine development and discuss their current status, challenges, and prospects.

  4. Comparative studies of types 1 and 2 herpes simplex virus infection of cultured normal keratinocytes.

    PubMed Central

    Su, S J; Wu, H H; Lin, Y H; Lin, H Y

    1995-01-01

    AIMS--To investigate the differences in biological properties, multiplication patterns, and cytopathic effects between type 1 and type 2 herpes simplex virus (HSV) through the replication of HSV in cultured normal human keratinocytes. METHODS--Keratinocytes were obtained from surgical specimens of normal gingiva, cervix, trunk skin, and newborn foreskin. They were cultured in serum free, chemically defined, culture medium and infected with a pool of HSV collected from clinical specimens. RESULTS--The reproductive patterns of HSV type 1 (HSV-1) and HSV type 2 (HSV-2) differed from each other regardless of the anatomical source of the cultured cells. This was made evident by the dissimilarity of their growth curves and cytopathic effects. The growth curve of HSV-2 showed a more or less continuously rising titre, whereas HSV-1 titres varied substantially at different time intervals. The cytopathic effects induced by HSV-1 infection took 24 more incubation hours than those induced by HSV-2 infection to manifest. During the early stages, the cytopathic changes of the two viruses looked different. However, all cultured cells, whether cultured with HSV-1 or HSV-2, eventually became small and globular in shape. The infective titres of both HSV-1 and HSV-2 were higher in infected cultured cervix than in infected cultured normal gingiva. CONCLUSIONS--These data suggest that each serotype of HSV has its own unique replication pattern in human keratinocytes regardless of the cell origin. Images PMID:7706526

  5. New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease.

    PubMed

    Kleymann, Gerald; Fischer, Rüdiger; Betz, Ulrich A K; Hendrix, Martin; Bender, Wolfgang; Schneider, Udo; Handke, Gabriele; Eckenberg, Peter; Hewlett, Guy; Pevzner, Veniamin; Baumeister, Judith; Weber, Olaf; Henninger, Kerstin; Keldenich, Jörg; Jensen, Axel; Kolb, Jörg; Bach, Ute; Popp, Andreas; Mäben, Jutta; Frappa, Isabelle; Haebich, Dieter; Lockhoff, Oswald; Rübsamen-Waigmann, Helga

    2002-04-01

    The vast majority of the world population is infected with at least one member of the human herpesvirus family. Herpes simplex virus (HSV) infections are the cause of cold sores and genital herpes as well as life-threatening or sight-impairing disease mainly in immunocompromized patients, pregnant women and newborns. Since the milestone development in the late 1970s of acyclovir (Zovirax), a nucleosidic inhibitor of the herpes DNA polymerase, no new non-nucleosidic anti-herpes drugs have been introduced. Here we report new inhibitors of the HSV helicase-primase with potent in vitro anti-herpes activity, a novel mechanism of action, a low resistance rate and superior efficacy against HSV in animal models. BAY 57-1293 (N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide), a well-tolerated member of this class of compounds, significantly reduces time to healing, prevents rebound of disease after cessation of treatment and, most importantly, reduces frequency and severity of recurrent disease. Thus, this class of drugs has significant potential for the treatment of HSV disease in humans, including those resistant to current medications. PMID:11927946

  6. The Telomerase Inhibitor MST-312 Interferes with Multiple Steps in the Herpes Simplex Virus Life Cycle

    PubMed Central

    Haberichter, Jarod; Roberts, Scott; Abbasi, Imran; Dedthanou, Phonphanh; Pradhan, Prajakta

    2015-01-01

    ABSTRACT The life cycle of herpes simplex virus (HSV) has the potential to be further manipulated to yield novel, more effective therapeutic treatments. Recent research has demonstrated that HSV-1 can increase telomerase activity and that expression of the catalytic component of telomerase, telomerase reverse transcriptase (TERT), alters sensitivity to HSV-dependent apoptosis. Telomerase is a cellular enzyme that synthesizes nucleotide repeats at the ends of chromosomes (telomeres), which prevents shortening of the 3′ ends of DNA with each cell division. Once telomeres reach a critical length, cells undergo senescence and apoptosis. Here, we used a cell-permeable, reversible inhibitor of the telomerase enzyme, MST-312, to investigate telomerase activity during HSV infection. Human mammary epithelial cells immortalized through TERT expression and human carcinoma HEp-2 cells were infected with the KOS1.1 strain of HSV-1 in the presence of MST-312. MST-312 treatment reduced the number of cells displaying a cytopathic effect and the accumulation of immediate early and late viral proteins. Moreover, the presence of 20 μM to 100 μM MST-312 during infection led to a 2.5- to 5.5-log10 decrease in viral titers. MST-312 also inhibited the replication of HSV-2 and a recent clinical isolate of HSV-1. Additionally, we determined that MST-312 has the largest impact on viral events that take place prior to 5 h postinfection (hpi). Furthermore, MST-312 treatment inhibited virus replication, as measured by adsorption assays and quantification of genome replication. Together, these findings demonstrate that MST-312 interferes with the HSV life cycle. Further investigation into the mechanism for MST-312 is warranted and may provide novel targets for HSV therapies. IMPORTANCE Herpes simplex virus (HSV) infections can lead to cold sores, blindness, and brain damage. Identification of host factors that are important for the virus life cycle may provide novel targets for HSV

  7. Basal Autophagy Is Required for Herpes simplex Virus-2 Infection

    PubMed Central

    Yakoub, Abraam M.; Shukla, Deepak

    2015-01-01

    Autophagy is a conserved catabolic process of the cell, which plays an important role in regulating plethora of infections. The role of autophagy in Herpes simplex virus-2 (HSV-2) infection is unknown. Here, we found that HSV-2 does not allow induction of an autophagic response to infection, but maintains basal autophagy levels mostly unchanged during productive infection. Thus, we investigated the importance of basal autophagy for HSV-2 infection, using pharmacological autophagy suppression or cells genetically deficient in an autophagy-essential gene (ATG5). Interference with basal autophagy flux in cells significantly reduced viral replication and diminished the infection. These results indicate that basal autophagy plays an indispensable role required for a productive infection. Importantly, this study draws a sharp distinction between induced and basal autophagy, where the former acts as a viral clearance mechanism abrogating infection, while the latter supports infection. PMID:26248741

  8. Anaerobic bacteria and herpes simplex virus in genital ulceration.

    PubMed Central

    Masfari, A N; Kinghorn, G R; Hafiz, S; Barton, I G; Duerden, B I

    1985-01-01

    Of 91 patients with genital ulceration, herpes simplex virus was isolated from 52 (57%) and Haemophilus ducreyi from 12 (13%); none had syphilis. The difference in incidence of other aerobes in patients and controls was not significant. Anaerobes, predominantly Bacteroides spp, were isolated from a large proportion (77%) of men and women patients with ulcers but from few control men. The most common anaerobic species were B asaccharolyticus and B ureolyticus, with fewer isolates of the melaninogenicus/oralis group. The bacterial flora of herpetic and non-herpetic ulcers were similar, but Candida albicans was isolated significantly more often from non-herpetic ulcers. Anaerobic bacteria may contribute to the pathogenesis of genital ulcers. PMID:2984108

  9. Analysis of test data on the simplex strapdown navigation system

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The results of a study of test data taken on the simplex strapdown navigation system were presented. That system consisted of the following components: strapdown platform, altimeter, digital computer, tape recorder, typewriter, and power source. The objective of these tests was to isolate error sources which may cause degradation of the system's accuracy and to recommend appropriate changes to the system test procedures or computer software. The following recommendations were made: (1) addition of a gyro compassing alignment program into the navigation program, (2) addition of line drivers at the signal processor end of the transmission line, (3) need for extensive laboratory testing to determine sensor misalignments, biases, and scale factors, (4) need to stabilize the power source to prevent transients during power transfer, (5) need to isolate and eliminate the source of the large noise inputs.

  10. Lytic Promoters Express Protein during Herpes Simplex Virus Latency

    PubMed Central

    Russell, Tiffany A.; Tscharke, David C.

    2016-01-01

    Herpes simplex virus (HSV) has provided the prototype for viral latency with previously well-defined acute or lytic and latent phases. More recently, the deep quiescence of HSV latency has been questioned with evidence that lytic genes can be transcribed in this state. However, to date the only evidence that these transcripts might be translated has come from immunological studies that show activated T cells persist in the nervous system during latency. Here we use a highly sensitive Cre-marking model to show that lytic and latent phases are less clearly defined in two significant ways. First, around half of the HSV spread leading to latently infected sites occurred beyond the initial acute infection and second, we show direct evidence that lytic promoters can drive protein expression during latency. PMID:27348812

  11. Herpes simplex virus 1 induces de novo phospholipid synthesis

    SciTech Connect

    Sutter, Esther; Oliveira, Anna Paula de; Tobler, Kurt; Schraner, Elisabeth M.; Sonda, Sabrina; Kaech, Andres; Lucas, Miriam S.; Ackermann, Mathias; Wild, Peter

    2012-08-01

    Herpes simplex virus type 1 capsids bud at nuclear membranes and Golgi membranes acquiring an envelope composed of phospholipids. Hence, we measured incorporation of phospholipid precursors into these membranes, and quantified changes in size of cellular compartments by morphometric analysis. Incorporation of [{sup 3}H]-choline into both nuclear and cytoplasmic membranes was significantly enhanced upon infection. [{sup 3}H]-choline was also part of isolated virions even grown in the presence of brefeldin A. Nuclei expanded early in infection. The Golgi complex and vacuoles increased substantially whereas the endoplasmic reticulum enlarged only temporarily. The data suggest that HSV-1 stimulates phospholipid synthesis, and that de novo synthesized phospholipids are inserted into nuclear and cytoplasmic membranes to i) maintain membrane integrity in the course of nuclear and cellular expansion, ii) to supply membrane constituents for envelopment of capsids by budding at nuclear membranes and Golgi membranes, and iii) to provide membranes for formation of transport vacuoles.

  12. Immunological Aspects of Acute and Recurrent Herpes Simplex Keratitis

    PubMed Central

    Hus, Iwona

    2014-01-01

    Herpes simplex keratitis (HSK) belongs to the major causes of visual morbidity worldwide and available methods of treatment remain unsatisfactory. Primary infection occurs usually early in life and is often asymptomatic. Chronic visual impairment and visual loss are caused by corneal scaring, thinning, and vascularization connected with recurrent HSV infections. The pathogenesis of herpetic keratitis is complex and is still not fully understood. According to the current knowledge, corneal scarring and vascularization are the result of chronic inflammatory reaction against HSV antigens. In this review we discuss the role of innate and adaptive immunities in acute and recurrent HSV ocular infection and present the potential future targets for novel therapeutical options based on immune interventions. PMID:25276842

  13. Transmission Disequilibrium of Small CNVs in Simplex Autism

    PubMed Central

    Krumm, Niklas; O’Roak, Brian J.; Karakoc, Emre; Mohajeri, Kiana; Nelson, Ben; Vives, Laura; Jacquemont, Sebastien; Munson, Jeff; Bernier, Raphe; Eichler, Evan E.

    2013-01-01

    We searched for disruptive, genic rare copy-number variants (CNVs) among 411 families affected by sporadic autism spectrum disorder (ASD) from the Simons Simplex Collection by using available exome sequence data and CoNIFER (Copy Number Inference from Exome Reads). Compared to high-density SNP microarrays, our approach yielded ∼2× more smaller genic rare CNVs. We found that affected probands inherited more CNVs than did their siblings (453 versus 394, p = 0.004; odds ratio [OR] = 1.19) and that the probands’ CNVs affected more genes (921 versus 726, p = 0.02; OR = 1.30). These smaller CNVs (median size 18 kb) were transmitted preferentially from the mother (136 maternal versus 100 paternal, p = 0.02), although this bias occurred irrespective of affected status. The excess burden of inherited CNVs among probands was driven primarily by sibling pairs with discordant social-behavior phenotypes (p < 0.0002, measured by Social Responsiveness Scale [SRS] score), which contrasts with families where the phenotypes were more closely matched or less extreme (p > 0.5). Finally, we found enrichment of brain-expressed genes unique to probands, especially in the SRS-discordant group (p = 0.0035). In a combined model, our inherited CNVs, de novo CNVs, and de novo single-nucleotide variants all independently contributed to the risk of autism (p < 0.05). Taken together, these results suggest that small transmitted rare CNVs play a role in the etiology of simplex autism. Importantly, the small size of these variants aids in the identification of specific genes as additional risk factors associated with ASD. PMID:24035194

  14. Gasification of Simplex briquets: briquet production. Vol. 1. Final report

    SciTech Connect

    Not Available

    1983-04-01

    A 7-ton/hr briquetting plant was installed at International Briquetting in Baltimore, Maryland, and used to produce 360 tons of Simplex briquets from Pittsburgh No. 8 seam, Champion No. 1 mine caking coal and shredded, air-classified Baltimore County refuse. The production of these briquets was funded by the Department of Energy, through the US Bureau of Mines, and a consortium comprised of the New York State Energy Research and Development Authority and the Empire State Electric Energy Research Company. This report describes the briquetting plant and discusses the problems that were encountered in producing the briquets. The following modifications are recommended for future Simplex briquetting plants: drying equipment should be installed on the RDF feed system to ensure that the RDF moisture is below 18%; the crushed coal must be dried to less than 4% moisture to ensure its free flow in the bins; magnets should be installed above the coal and RDF feed conveyors to remove any tramp metal; a 3/4-inch screen should be installed over the coal feed bin to remove any oversize rocks or lump coal; the RDF handling system and turbulizer discharge to the press should all be enclosed for dust control (the enclosures should be vented to a baghouse); only heavy duty apron conveyors should be used where belt conveyors are needed; briquetts should be cured if they are going to be stored in containers where they might sweat; and a screen with 1 1/4-inch openings should be used to remove the fines from 2 1/4-inch briquets (this screen should be sufficiently large to prevent briquets from crowding together on the screen).

  15. Bionomics of Orasema simplex (Hymenoptera: Eucharitidae) a parasitoid of Solenopsis fire ants (Hymenoptera: Formicidae) in Argentina

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biological characteristics of the parasitoid Orasema simplex Heraty (Hymenoptera: Eucharitidae), a potential candidate for the biological control of fire ants in the United States were investigated. Female survivorship, fertility and oviposition preferences were studied in the laboratory. Naturally ...

  16. Disseminated herpes simplex infection during pregnancy, rare but important to recognise.

    PubMed

    Hussain, Nawar Younis; Uriel, Alison; Mammen, Catherine; Bonington, Alec

    2014-01-01

    Disseminated herpes simplex virus (HSV) infection during pregnancy is a rare, but potentially fatal condition. We present a case where prompt treatment with intravenous acyclovir resulted in a successful outcome for both mother and baby.

  17. Inhibition of Ataxia Telangiectasia Mutated (ATM) Kinase Suppresses Herpes Simplex Virus Type 1 (HSV-1) Keratitis

    PubMed Central

    Alekseev, Oleg; Donovan, Kelly; Azizkhan-Clifford, Jane

    2014-01-01

    Purpose. Herpes keratitis (HK) remains the leading cause of cornea-derived blindness in the developed world, despite the availability of effective antiviral drugs. Treatment toxicity and the emergence of drug resistance highlight the need for additional therapeutic approaches. This study examined ataxia telangiectasia mutated (ATM), an apical kinase in the host DNA damage response, as a potential new target for the treatment of HK. Methods. Small molecule inhibitor of ATM (KU-55933) was used to treat herpes simplex virus type 1 (HSV-1) infection in three experimental models: (1) in vitro—cultured human corneal epithelial cells, hTCEpi, (2) ex vivo—organotypically explanted human and rabbit corneas, and (3) in vivo—corneal infection in young C57BL/6J mice. Infection productivity was assayed by plaque assay, real-time PCR, Western blot, and disease scoring. Results. Robust ATM activation was detected in HSV-1-infected human corneal epithelial cells. Inhibition of ATM greatly suppressed viral replication in cultured cells and in explanted human and rabbit corneas, and reduced the severity of stromal keratitis in mice. The antiviral effect of KU-55933 in combination with acyclovir was additive, and KU-55933 suppressed replication of a drug-resistant HSV-1 strain. KU-55933 caused minimal toxicity, as monitored by clonogenic survival assay and fluorescein staining. Conclusions. This study identifies ATM as a potential target for the treatment of HK. ATM inhibition by KU-55933 reduces epithelial infection and stromal disease severity without producing appreciable toxicity. These findings warrant further investigations into the DNA damage response as an area for therapeutic intervention in herpetic ocular diseases. PMID:24370835

  18. Anti-N-Methyl-D-Aspartate Receptor Antibody Mediated Neurologic Relapse Post Herpes Simplex Encephalitis: A Case Series.

    PubMed

    Geoghegan, Sarah; Walsh, Aoibhinn; King, Mary D; Lynch, Bryan; Webb, David; Twomey, Eilish; Ronan Leahy, T; Butler, Karina; Gavin, Patrick

    2016-08-01

    Despite the advent of antiviral therapy, herpes simplex encephalitis (HSE) remains a devastating condition with significant morbidity and mortality. Neurologic relapse after initial improvement is generally attributed to herpes simplex virus reactivation. In 2013, inflammation caused by anti-N-methyl-D-aspartate receptor antibodies was reported in association with cases of neurologic relapse after herpes simplex encephalitis. We present 3 such cases and discuss diagnostic and management dilemmas.

  19. Houttuynia cordata targets the beginning stage of herpes simplex virus infection.

    PubMed

    Hung, Pei-Yun; Ho, Bing-Ching; Lee, Szu-Yuan; Chang, Sui-Yuan; Kao, Chuan-Liang; Lee, Shoei-Sheng; Lee, Chun-Nan

    2015-01-01

    Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV.

  20. Oligonucleotides designed to inhibit TLR9 block Herpes simplex virus type 1 infection at multiple steps.

    PubMed

    Sauter, Monica M; Gauger, Joshua J L; Brandt, Curtis R

    2014-09-01

    Herpes simplex virus type 1 (HSV-1) is an important human pathogen which requires activation of nuclear factor-kappa B (NFκB) during its replication cycle. The persistent nature of HSV-1 infection, and the emergence of drug-resistant strains, highlights the importance of research to develop new antiviral agents. Toll-like receptors (TLRs) play a prominent role during the early antiviral response by recognizing viral nucleic acid and gene products, activating NFκB, and stimulating the production of inflammatory cytokines. We demonstrate a significant effect on HSV-1 replication in ARPE-19 and Vero cells when oligonucleotides designed to inhibit TLR9 are added 2h prior to infection. A greater than 90% reduction in the yield of infectious virus was achieved at oligonucleotide concentrations of 10-20 μM. TLR9 inhibitory oligonucleotides prevented expression of essential immediate early herpes gene products as determined by immunofluorescence microscopy and Western blotting. TLR9 oligonucleotides also interfered with viral attachment and entry. A TLR9 inhibitory oligonucleotide containing five adjacent guanosine residues (G-ODN) exhibited virucidal activity and inhibited HSV-1 replication when added post-infection. The antiviral effect of the TLR9 inhibitory oligonucleotides did not depend on the presence of TLR9 protein, suggesting a mechanism of inhibition that is not TLR9 specific. TLR9 inhibitory oligonucleotides also reduced NFκB activity in nuclear extracts. Studies using these TLR inhibitors in the context of viral infection should be interpreted with caution.

  1. Structural analysis of herpes simplex virus by optical super-resolution imaging.

    PubMed

    Laine, Romain F; Albecka, Anna; van de Linde, Sebastian; Rees, Eric J; Crump, Colin M; Kaminski, Clemens F

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.

  2. Functional IRF3 deficiency in a patient with herpes simplex encephalitis.

    PubMed

    Andersen, Line Lykke; Mørk, Nanna; Reinert, Line S; Kofod-Olsen, Emil; Narita, Ryo; Jørgensen, Sofie E; Skipper, Kristian A; Höning, Klara; Gad, Hans Henrik; Østergaard, Lars; Ørntoft, Torben F; Hornung, Veit; Paludan, Søren R; Mikkelsen, Jacob Giehm; Fujita, Takashi; Christiansen, Mette; Hartmann, Rune; Mogensen, Trine H

    2015-08-24

    Herpes simplex encephalitis (HSE) in children has previously been linked to defects in type I interferon (IFN) production downstream of Toll-like receptor 3. Here, we describe a novel genetic etiology of HSE by identifying a heterozygous loss-of-function mutation in the IFN regulatory factor 3 (IRF3) gene, leading to autosomal dominant (AD) IRF3 deficiency by haploinsufficiency, in an adolescent female patient with HSE. IRF3 is activated by most pattern recognition receptors recognizing viral infections and plays an essential role in induction of type I IFN. The identified IRF3 R285Q amino acid substitution results in impaired IFN responses to HSV-1 infection and particularly impairs signaling through the TLR3-TRIF pathway. In addition, the R285Q mutant of IRF3 fails to become phosphorylated at S386 and undergo dimerization, and thus has impaired ability to activate transcription. Finally, transduction with WT IRF3 rescues the ability of patient fibroblasts to express IFN in response to HSV-1 infection. The identification of IRF3 deficiency in HSE provides the first description of a defect in an IFN-regulating transcription factor conferring increased susceptibility to a viral infection in the CNS in humans.

  3. Herpes simplex virus type 1 infection in mice with severe combined immunodeficiency (SCID).

    PubMed

    Minagawa, H; Sakuma, S; Mohri, S; Mori, R; Watanabe, T

    1988-01-01

    Herpes simplex virus type 1 (HSV-1) infection in mutant mice with severe combined immunodeficiency (SCID mice), i.e., mice in which the differentiation of both T and B lymphocytes is severely impaired, was studied. All control (infected and not treated with antibodies or with immune spleen cells) SCID mice were dead by 17 days after intracutaneous injection in the right midflank with 1 x 10(5) PFU of a virulent HSV-1 strain, Hayashida. Immunization with an avirulent strain of HSV-1 (SKa) did not protect them from death or prolong the survival time. Tissue virus titration of infected mice killed at various times after inoculation detected infectious virus in various organs, dorsal root ganglia, spinal cord, brain, kidney and adrenal gland in addition to the inoculation site of the skin in SCID mice, whereas virus could be detected only in the inoculation site and the nervous tissues in euthymic BALB/c mice, and in the adrenal gland from only one out of 17 nude mice. Human gamma globulin containing neutralizing antibody against HSV-1 prolonged the survival time but did not protect SCID mice from death. Transfer of spleen cells from immunized BALB/c mice protected the infected SCID mice from death. Treatment of spleen cells with anti-Thy 1.2 monoclonal antibody and complement abolished the protection.

  4. Asymptomatic vaginal herpes simplex virus infections in mice: virology and pathohistology.

    PubMed

    Podlech, J; Hengerer, F; Fleck, M; Eray, K; D Falke

    1996-01-01

    One of the causes of genital tract infections in humans are herpes simplex virus types 1 and 2 (HSV-1, HSV-2). Although primary and recurrent infections can be clinically apparent and in part very serious, many infections are asymptomatic and result only in temporary genital shedding of virus (recurrences). During our investigations of vaginitis, strain IES of HSV-1 produced an asymptomatic infection. Replication in the murine vaginal (vag.) epithelium as well as antibody formation after vag. infection was comparable to those of survivors after infection with highly virulent strains. Titration of liver, spleen, ovaries, adrenal glands spinal cord, or brain after vag. IES infection revealed no virus, whereas after i.p. infection virus could be demonstrated in many organs examined. Histological examination with a DNA probe (in situ hybridisation), HSV antibodies (immunohistochemistry), and haematoxylin and eosin (HE) staining showed only small focal HSV lesions of the vaginal epithelium in early stages of the infection, never exceeding to the subepithelial tissue. Severe infiltrations and ulcerations after infection with highly virulent strains (17syn +, ER-) could never be demonstrated after IES vag. infection. Identical replication rates of both groups of HSV despite much greater areas of epithelial necrosis with the virulent strains may be explained by the large number of virus inactivating granulocytes induced by the virulent strains, thus inactivating the hypothetical higher virus load.

  5. VP22 herpes simplex virus protein can transduce proteins into stem cells.

    PubMed

    Gabanyi, I; Lojudice, F H; Kossugue, P M; Rebelato, E; Demasi, M A; Sogayar, M C

    2013-02-01

    The type I herpes simplex virus VP22 tegument protein is abundant and well known for its ability to translocate proteins from one cell to the other. In spite of some reports questioning its ability to translocate proteins by attributing the results observed to fixation artifacts or simple attachment to the cell membrane, VP22 has been used to deliver several proteins into different cell types, triggering the expected cell response. However, the question of the ability of VP22 to enter stem cells has not been addressed. We investigated whether VP22 could be used as a tool to be applied in stem cell research and differentiation due to its capacity to internalize other proteins without altering the cell genome. We generated a VP22.eGFP construct to evaluate whether VP22 could be internalized and carry another protein with it into two different types of stem cells, namely adult human dental pulp stem cells and mouse embryonic stem cells. We generated a VP22.eGFP fusion protein and demonstrated that, in fact, it enters stem cells. Therefore, this system may be used as a tool to deliver various proteins into stem cells, allowing stem cell research, differentiation and the generation of induced pluripotent stem cells in the absence of genome alterations.

  6. Functional IRF3 deficiency in a patient with herpes simplex encephalitis

    PubMed Central

    Andersen, Line Lykke; Mørk, Nanna; Reinert, Line S.; Kofod-Olsen, Emil; Narita, Ryo; Jørgensen, Sofie E.; Skipper, Kristian A.; Höning, Klara; Gad, Hans Henrik; Østergaard, Lars; Ørntoft, Torben F.; Hornung, Veit; Paludan, Søren R.; Mikkelsen, Jacob Giehm; Fujita, Takashi; Christiansen, Mette; Hartmann, Rune

    2015-01-01

    Herpes simplex encephalitis (HSE) in children has previously been linked to defects in type I interferon (IFN) production downstream of Toll-like receptor 3. Here, we describe a novel genetic etiology of HSE by identifying a heterozygous loss-of-function mutation in the IFN regulatory factor 3 (IRF3) gene, leading to autosomal dominant (AD) IRF3 deficiency by haploinsufficiency, in an adolescent female patient with HSE. IRF3 is activated by most pattern recognition receptors recognizing viral infections and plays an essential role in induction of type I IFN. The identified IRF3 R285Q amino acid substitution results in impaired IFN responses to HSV-1 infection and particularly impairs signaling through the TLR3–TRIF pathway. In addition, the R285Q mutant of IRF3 fails to become phosphorylated at S386 and undergo dimerization, and thus has impaired ability to activate transcription. Finally, transduction with WT IRF3 rescues the ability of patient fibroblasts to express IFN in response to HSV-1 infection. The identification of IRF3 deficiency in HSE provides the first description of a defect in an IFN-regulating transcription factor conferring increased susceptibility to a viral infection in the CNS in humans. PMID:26216125

  7. Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

    PubMed Central

    Schiffer, Joshua T; Corey, Lawrence

    2014-01-01

    Herpes Simplex Virus-2 (HSV-2) is episodically shed throughout the human genital tract. While high viral load correlates with development of genital ulcers, shedding also commonly occurs even when ulcers are not present, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs despite diverse and complementary host and viral mechanisms within ganglionic tissue that predispose towards latency, suggesting that viral replication may be constantly occurring in a small minority of neurons within the ganglia. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-specific T cells persist at prior sites of genital tract reactivation, and in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. Shedding episodes vary greatly in duration and severity within a single person over time: this heterogeneity appears best explained by variation in the densities of host immunity across the genital tract. The fact that immune responses usually control viral replication in genital skin prior to development of lesions provides optimism that enhancing such responses could lead to effective vaccines and immunotherapies. PMID:23467247

  8. Houttuynia cordata Targets the Beginning Stage of Herpes Simplex Virus Infection

    PubMed Central

    Hung, Pei-Yun; Ho, Bing-Ching; Lee, Szu-Yuan; Chang, Sui-Yuan; Kao, Chuan-Liang; Lee, Shoei-Sheng; Lee, Chun-Nan

    2015-01-01

    Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV. PMID:25643242

  9. Houttuynia cordata targets the beginning stage of herpes simplex virus infection.

    PubMed

    Hung, Pei-Yun; Ho, Bing-Ching; Lee, Szu-Yuan; Chang, Sui-Yuan; Kao, Chuan-Liang; Lee, Shoei-Sheng; Lee, Chun-Nan

    2015-01-01

    Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV. PMID:25643242

  10. Genetic Diversity within Alphaherpesviruses: Characterization of a Novel Variant of Herpes Simplex Virus 2

    PubMed Central

    Désiré, Nathalie; Marlet, Julien; Dacheux, Laurent; Seang, Sophie; Caumes, Eric; Bourhy, Hervé; Agut, Henri; Boutolleau, David

    2015-01-01

    ABSTRACT Very low levels of variability have been reported for the herpes simplex virus 2 (HSV-2) genome. We recently described a new genetic variant of HSV-2 (HSV-2v) characterized by a much higher degree of variability for the UL30 gene (DNA polymerase) than observed for the HG52 reference strain. Retrospective screening of 505 clinical isolates of HSV-2 by a specific real-time PCR assay targeting the UL30 gene led to the identification of 13 additional HSV-2v isolates, resulting in an overall prevalence of 2.8%. Phylogenetic analyses on the basis of microsatellite markers and gene sequences showed clear differences between HSV-2v and classical HSV-2. Thirteen of the 14 patients infected with HSV-2v originated from West or Central Africa, and 9 of these patients were coinfected with HIV. These results raise questions about the origin of this new virus. Preliminary results suggest that HSV-2v may have acquired genomic segments from chimpanzee alphaherpesvirus (ChHV) by recombination. IMPORTANCE This article deals with the highly topical question of the origin of this new HSV-2 variant identified in patients with HIV coinfection originating mostly from West or Central Africa. HSV-2v clearly differed from classical HSV-2 isolates in phylogenetic analyses and may be linked to simian ChHV. This new HSV-2 variant highlights the possible occurrence of recombination between human and simian herpesviruses under natural conditions, potentially presenting greater challenges for the future. PMID:26401046

  11. Biosafety of gene therapy vectors derived from herpes simplex virus type 1.

    PubMed

    Lim, Filip; Khalique, Hena; Ventosa, Maria; Baldo, Aline

    2013-12-01

    The majority of humans have been infected with Herpes Simplex Virus Type 1 (HSV-1) and harbor its viral DNA in the latent form within neurons for lifetime. This, combined with the absence of serious adverse effects due to HSV-1 derived vectors in clinical trials so far, highlight the potential to use this virus to develop neuronal gene transfer vectors which are transparent to the host, allowing the effects of the transgene to act without interference from the transfer system eg., for functional genomics in basic neuroscience or gene therapy of neurological disorders. On the other hand, other HSV-1 derived vectors which also have a promising perspective in the clinic, are designed to have enhanced cytotoxicity in certain cell types, as in the case of oncolytic vectors. Understanding virus-host interactions is fundamental not only to the success of these gene therapy vectors but also with respect to identifying and minimizing biohazards associated with their use. In this review we discuss characteristics of HSV-1 and gene therapy vectors derived from this virus which are useful to consider in the context of biosafety risk assessment and risk management.

  12. VP22 herpes simplex virus protein can transduce proteins into stem cells

    PubMed Central

    Gabanyi, I.; Lojudice, F.H.; Kossugue, P.M.; Rebelato, E.; Demasi, M.A.; Sogayar, M.C.

    2013-01-01

    The type I herpes simplex virus VP22 tegument protein is abundant and well known for its ability to translocate proteins from one cell to the other. In spite of some reports questioning its ability to translocate proteins by attributing the results observed to fixation artifacts or simple attachment to the cell membrane, VP22 has been used to deliver several proteins into different cell types, triggering the expected cell response. However, the question of the ability of VP22 to enter stem cells has not been addressed. We investigated whether VP22 could be used as a tool to be applied in stem cell research and differentiation due to its capacity to internalize other proteins without altering the cell genome. We generated a VP22.eGFP construct to evaluate whether VP22 could be internalized and carry another protein with it into two different types of stem cells, namely adult human dental pulp stem cells and mouse embryonic stem cells. We generated a VP22.eGFP fusion protein and demonstrated that, in fact, it enters stem cells. Therefore, this system may be used as a tool to deliver various proteins into stem cells, allowing stem cell research, differentiation and the generation of induced pluripotent stem cells in the absence of genome alterations. PMID:23369972

  13. Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity

    PubMed Central

    Miyagawa, Yoshitaka; Marino, Pietro; Verlengia, Gianluca; Uchida, Hiroaki; Goins, William F.; Yokota, Shinichiro; Geller, David A.; Yoshida, Osamu; Mester, Joseph; Cohen, Justus B.; Glorioso, Joseph C.

    2015-01-01

    The design of highly defective herpes simplex virus (HSV) vectors for transgene expression in nonneuronal cells in the absence of toxic viral-gene activity has been elusive. Here, we report that elements of the latency locus protect a nonviral promoter against silencing in primary human cells in the absence of any viral-gene expression. We identified a CTCF motif cluster 5′ to the latency promoter and a known long-term regulatory region as important elements for vigorous transgene expression from a vector that is functionally deleted for all five immediate-early genes and the 15-kb internal repeat region. We inserted a 16.5-kb expression cassette for full-length mouse dystrophin and report robust and durable expression in dystrophin-deficient muscle cells in vitro. Given the broad cell tropism of HSV, our design provides a nontoxic vector that can accommodate large transgene constructs for transduction of a wide variety of cells without vector integration, thereby filling an important void in the current arsenal of gene-therapy vectors. PMID:25775541

  14. Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication

    PubMed Central

    Gu, Haidong

    2016-01-01

    Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced “conquer and compromise” strategy to deal with the host anti-viral defenses. One of HSV-1 α (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host. PMID:26870669

  15. Activity of Tea Tree (Melaleuca alternifolia) Essential Oil against L3 Larvae of Anisakis simplex

    PubMed Central

    Langa, Elisa; Murillo, Paula

    2014-01-01

    Nematicidal activity of Melaleuca alternifolia essential oil, commonly known as tea tree oil (TTO), was assayed in vitro against L3 larvae of Anisakis simplex. The results showed a mortality of 100% for concentrations between 7 and 10 μL/mL after 48 h of incubation, obtaining an LD50 value of 4.53 μL/mL after 24 hours and 4.27 μL/mL after 48 hours. Concentration-dependent inhibition of acetylcholinesterase was observed for tea tree essential oil showing inhibition values of 100% at 100 μL/mL. This fact suggests that TTO may act as an AChE inhibitor. Terpinen-4-ol was discarded as main larvicide compound as it did not show larvicidal or anticholinesterase activity. The data obtained suggest that the essential oil of Melaleuca alternifolia may have a great therapeutic potential for the treatment of human anisakiasis. PMID:24967378

  16. Toxicity studies in thymidine kinase-deficient herpes simplex virus therapy for malignant astrocytoma.

    PubMed

    Jia, W W; Tan, J; Redekop, G J; Goldie, J H

    1996-10-01

    Previous studies have shown that genetically engineered thymidine kinase (tk)-defective herpes simplex virus type 1 (HSV-1) can effectively and selectively destroy gliomas in animal models. The consequences of viral infection and tumor regression must be characterized before this therapy can be applied in human trials. To study the potential for long-term toxicity, immunocompetent rats harboring 9L gliosarcomas were injected intratumorally with a tk-defective HSV-1, KOS-SB, at titers that previously have been demonstrated to cause tumor regression. In animals surviving 3 months or longer following viral treatment, there was no evidence of persistent infection or inflammation in peritumoral brain tissue or in remote systemic organs studied with routine histological and immunocytochemical analyses. Polymerase chain reaction using primers specific for HSV-1 detected HSV-1 DNA in peritumoral tissue only in animals sacrificed within 3 months of viral injection. There was no evidence of HSV-1 DNA in systemic tissues at any time after treatment. We conclude that stereotactic intratumoral injection of tk-deficient HSV can be attempted for the treatment of brain tumors without risk of systemic infection or significant toxicity to normal brain or remote proliferating tissues. PMID:8814171

  17. Low- and high-intensity lasers in the treatment of herpes simplex virus 1 infection.

    PubMed

    Bello-Silva, Marina Stella; de Freitas, Patricia Moreira; Aranha, Ana Cecília Corrêa; Lage-Marques, José Luiz; Simões, Alyne; de Paula Eduardo, Carlos

    2010-02-01

    Herpes simplex virus (HSV) is one of the most common viral infections of the human being. Although most of the seropositive persons do not manifest symptoms, infected individuals may present recurrent infections, characterized by cold sores. HSV-1 infection can result in potentially harmful complications in some patients, especially in those with compromised immunity. We report a clinical case of a patient with severe oral HSV-1 infection in the lower lip. The treatment of the lesions with the association of high-intensity (erbium-doped yttrium aluminum garnet, 2.94 mum, 80 mJ/pulse, 2-4 Hz) and low-intensity (indium gallium aluminum phosphide, 660 nm, 3.8 J/cm(2), 10 mW) lasers has not been reported in the literature. During treatment, no systemic or topical medication was used. Pain sensitivity was completely gone after the first irradiation with the low-intensity laser. During the healing process, lesions were traumatized twice, on the days 4 and 7. Even though the lesions were completely healed within 10 days. PMID:19712025

  18. Structural analysis of herpes simplex virus by optical super-resolution imaging

    NASA Astrophysics Data System (ADS)

    Laine, Romain F.; Albecka, Anna; van de Linde, Sebastian; Rees, Eric J.; Crump, Colin M.; Kaminski, Clemens F.

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.

  19. Woodylides A-C, new cytotoxic linear polyketides from the South China Sea sponge Plakortis simplex.

    PubMed

    Yu, Hao-Bing; Liu, Xiang-Fang; Xu, Ying; Gan, Jian-Hong; Jiao, Wei-Hua; Shen, Yang; Lin, Hou-Wen

    2012-05-01

    Three new polyketides, woodylides A-C (1-3), were isolated from the ethanol extract of the South China Sea sponge Plakortis simplex. The structures were elucidated by spectroscopic data (IR, 1D and 2D NMR, and HRESIMS). The absolute configurations at C-3 of 1 and 3 were determined by the modified Mosher's method. Antifungal, cytotoxic, and PTP1B inhibitory activities of these polyketides were evaluated. Compounds 1 and 3 showed antifungal activity against fungi Cryptococcus neoformans with IC₅₀ values of 3.67 and 10.85 µg/mL, respectively. In the cytotoxicity test, compound 1 exhibited a moderate effect against the HeLa cell line with an IC₅₀ value of 11.2 µg/mL, and compound 3 showed cytotoxic activity against the HCT-116 human colon tumor cell line and PTP1B inhibitory activity with IC₅₀ values of 9.4 and 4.7 µg/mL, respectively.

  20. Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector.

    PubMed

    Taylor, Travis J; Diaz, Fernando; Colgrove, Robert C; Bernard, Kristen A; DeLuca, Neal A; Whelan, Sean P J; Knipe, David M

    2016-09-01

    West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8(+) T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus.

  1. Reversible nerve damage and corneal pathology in murine herpes simplex stromal keratitis.

    PubMed

    Yun, Hongmin; Rowe, Alexander M; Lathrop, Kira L; Harvey, Stephen A K; Hendricks, Robert L

    2014-07-01

    Herpes simplex virus type 1 (HSV-1) shedding from sensory neurons can trigger recurrent bouts of herpes stromal keratitis (HSK), an inflammatory response that leads to progressive corneal scarring and blindness. A mouse model of HSK is often used to delineate immunopathogenic mechanisms and bears many of the characteristics of human disease, but it tends to be more chronic and severe than human HSK. Loss of blink reflex (BR) in human HSK is common and due to a dramatic retraction of corneal sensory nerve termini in the epithelium and the nerve plexus at the epithelial/stromal interface. However, the relationship between loss of BR due to nerve damage and corneal pathology associated with HSK remains largely unexplored. Here, we show a similar retraction of corneal nerves in mice with HSK. Indeed, we show that much of the HSK-associated corneal inflammation in mice is actually attributable to damage to the corneal nerves and accompanying loss of BR and can be prevented or ameliorated by tarsorrhaphy (suturing eyelids closed), a clinical procedure commonly used to prevent corneal exposure and desiccation. In addition, we show that HSK-associated nerve retraction, loss of BR, and severe pathology all are reversible and regulated by CD4(+) T cells. Thus, defining immunopathogenic mechanisms of HSK in the mouse model will necessitate distinguishing mechanisms associated with the immunopathologic response to the virus from those associated with loss of corneal sensation. Based on our findings, investigation of a possible contribution of nerve damage and BR loss to human HSK also appears warranted. Importance: HSK in humans is a potentially blinding disease characterized by recurrent inflammation and progressive scarring triggered by viral release from corneal nerves. Corneal nerve damage is a known component of HSK, but the causes and consequences of HSK-associated nerve damage remain obscure. We show that desiccation of the corneal surface due to nerve damage and

  2. Quantification of Anisakis simplex allergens in fresh, long-term frozen, and cooked fish muscle.

    PubMed

    Rodríguez-Mahillo, Ana Isabel; González-Muñoz, Miguel; de las Heras, Cristina; Tejada, Margarita; Moneo, Ignacio

    2010-08-01

    Fish-borne parasitic zoonoses such as Anisakiasis were once limited to people living in countries where raw or undercooked fish is traditionally consumed. Nowadays, several factors, such as the growing international markets, the improved transportation systems, the population movements, and the expansion of ethnic ways of cooking in developed countries, have increased the population exposed to these parasites. Improved diagnosis technology and a better knowledge of the symptoms by clinicians have increased the Anisakiasis cases worldwide. Dietary recommendations to Anisakis-sensitized patients include the consumption of frozen or well-cooked fish, but these probably do not defend sensitized patients from allergen exposure. The aim of our work was to develop a sensitive and specific method to detect and quantify Anisakis simplex allergens in fish muscle and its derivatives. Protein extraction was made in saline buffer followed by preparation under acid conditions. A. simplex antigens were detected by IgG immunoblot and quantified by dot blot. The allergenic properties of the extracts were assessed by IgE immunoblotting and basophil activation test. We were able to detect less than 1 ppm of A. simplex antigens, among them the allergen Ani s 4, in fish muscle with no cross-reactions and with a recovery rate of 82.5%. A. simplex antigens were detected in hakes and anchovies but not in sardines, red mullets, or shellfish. We detected A. simplex allergens in cooked hakes and also in hake stock. We proved that A. simplex allergens are preserved in long-term frozen storage (-20 degrees C +/- 2 degrees C for 11 months) of parasitized hakes. Basophil activation tests have proven the capability of the A. simplex-positive fish extracts to induce allergic symptoms.

  3. Evaluation of PD 404,182 as an Anti-HIV and Anti-Herpes Simplex Virus Microbicide

    PubMed Central

    Chamoun-Emanuelli, Ana M.; Bobardt, Michael; Moncla, Bernard; Mankowski, Marie K.; Ptak, Roger G.

    2014-01-01

    PD 404,182 (PD) is a synthetic compound that was found to compromise HIV integrity via interaction with a nonenvelope protein viral structural component (A. M. Chamoun et al., Antimicrob. Agents Chemother. 56:672–681, 2012). The present study evaluates the potential of PD as an anti-HIV microbicide and establishes PD's virucidal activity toward another pathogen, herpes simplex virus (HSV). We show that the anti-HIV-1 50% inhibitory concentration (IC50) of PD, when diluted in seminal plasma, is ∼1 μM, similar to the IC50 determined in cell culture growth medium, and that PD retains full anti-HIV-1 activity after incubation in cervical fluid at 37°C for at least 24 h. In addition, PD is nontoxic toward vaginal commensal Lactobacillus species (50% cytotoxic concentration [CC50], >300 μM), freshly activated human peripheral blood mononuclear cells (CC50, ∼200 μM), and primary CD4+ T cells, macrophages, and dendritic cells (CC50, >300 μM). PD also exhibited high stability in pH-adjusted Dulbecco's phosphate-buffered saline with little to no activity loss after 8 weeks at pH 4 and 42°C, indicating suitability for formulation for transportation and storage in developing countries. Finally, for the first time, we show that PD inactivates herpes simplex virus 1 (HSV-1) and HSV-2 at submicromolar concentrations. Due to the prevalence of HSV infection, the ability of PD to inactivate HSV may provide an additional incentive for use as a microbicide. The ability of PD to inactivate both HIV-1 and HSV, combined with its low toxicity and high stability, warrants additional studies for the evaluation of PD's microbicidal candidacy in animals and humans. PMID:24217696

  4. Simplex Factor Models for Multivariate Unordered Categorical Data

    PubMed Central

    Bhattacharya, Anirban; Dunson, David B.

    2013-01-01

    Gaussian latent factor models are routinely used for modeling of dependence in continuous, binary, and ordered categorical data. For unordered categorical variables, Gaussian latent factor models lead to challenging computation and complex modeling structures. As an alternative, we propose a novel class of simplex factor models. In the single-factor case, the model treats the different categorical outcomes as independent with unknown marginals. The model can characterize flexible dependence structures parsimoniously with few factors, and as factors are added, any multivariate categorical data distribution can be accurately approximated. Using a Bayesian approach for computation and inferences, a Markov chain Monte Carlo (MCMC) algorithm is proposed that scales well with increasing dimension, with the number of factors treated as unknown. We develop an efficient proposal for updating the base probability vector in hierarchical Dirichlet models. Theoretical properties are described, and we evaluate the approach through simulation examples. Applications are described for modeling dependence in nucleotide sequences and prediction from high-dimensional categorical features. PMID:23908561

  5. The herpes simplex virus virion host shutoff function.

    PubMed

    Kwong, A D; Frenkel, N

    1989-11-01

    The virion host shutoff (vhs) function of herpes simplex virus (HSV) limits the expression of genes in the infected cells by destabilizing both host and viral mRNAs. vhs function mutants have been isolated which are defective in their ability to degrade host mRNA. Furthermore, the half-life of viral mRNAs is significantly longer in cells infected with the vhs-1 mutant virus than in cells infected with the wild-type (wt) virus. Recent data have shown that the vhs-1 mutation resides within the open reading frame UL41. We have analyzed the shutoff of host protein synthesis in cells infected with a mixture of the wt HSV-1 (KOS) and the vhs-1 mutant virus. The results of these experiments revealed that (i) the wt virus shutoff activity requires a threshold level of input virions per cell and (ii) the mutant vhs-1 virus protein can irreversibly block the wt virus shutoff activity. These results are consistent with a stoichiometric model in which the wt vhs protein interacts with a cellular factor which controls the half-life of cell mRNA. This wt virus interaction results in the destabilization of both host and viral mRNAs. In contrast, the mutant vhs function interacts with the cellular factor irreversibly, resulting in the increased half-life of both host and viral mRNAs.

  6. Herpes simplex virus infections in neonates and early childhood.

    PubMed

    Kimberlin, David W

    2005-10-01

    Of the commonly considered congenital infections, those caused by cytomegalovirus (CMV), syphilis, and herpes simplex virus (HSV) are frequently (CMV, HSV) or exclusively (syphilis) acquired sexually by the mother, with subsequent transmission to the developing fetus. Of the other commonly considered congenital infections, including rubella and toxoplasma infections, the mother is exposed to the infectious agent via interpersonal or environmental contacts. Unlike each of these other pathogens, which are transmitted transplacentally to the developing fetus following maternal infection though, HSV usually is transmitted perinatally as the neonate is exposed to the virus during passage through an infected birth canal. This difference in timing of acquisition of infection has had important consequence in the therapeutic advances achieved during the last 30 years in the management of neonatal HSV infections. Because the time period between the acquisition of infection and initiation of effective antiviral therapy is shorter in neonatal herpes than in congenital toxoplasmosis or CMV infections, the outcomes of therapy have the potential to be markedly different. This article will summarize the current state of neonatal HSV disease presentation, diagnosis, and management. PMID:16210107

  7. Herpes Simplex Virus and Varicella-Zoster Virus.

    PubMed

    Levin, Myron J; Weinberg, Adriana; Schmid, D Scott

    2016-06-01

    The most common specimens from immunocompromised patients that are analyzed for detection of herpes simplex virus (HSV) or varicella-zoster virus (VZV) are from skin lesions. Many types of assays are applicable to these samples, but some, such as virus isolation and direct fluorescent antibody testing, are useful only in the early phases of the lesions. In contrast, nucleic acid (NA) detection methods, which generally have superior sensitivity and specificity, can be applied to skin lesions at any stage of progression. NA methods are also the best choice, and sometimes the only choice, for detecting HSV or VZV in blood, cerebrospinal fluid, aqueous or vitreous humor, and from mucosal surfaces. NA methods provide the best performance when reliability and speed (within 24 hours) are considered together. They readily distinguish the type of HSV detected or the source of VZV detected (wild type or vaccine strain). Nucleic acid detection methods are constantly being improved with respect to speed and ease of performance. Broader applications are under study, such as the use of quantitative results of viral load for prognosis and to assess the efficacy of antiviral therapy. PMID:27337486

  8. Bioactive lignan derivatives from the stems of Firmiana simplex.

    PubMed

    Woo, Kyeong Wan; Suh, Won Se; Subedi, Lalita; Kim, Sun Yeou; Kim, Aejung; Lee, Kang Ro

    2016-02-01

    The CHCl3 soluble fraction of the 80% MeOH extract of the stems of Firmiana simplex strongly inhibited nitric oxide production in lipopolysaccharide-activated BV-2 cells. A bioactivity-guided column chromatographic separation yielded two new lignans, firmianols A and B (1-2) together with seventeen known lignans (3-19). The structural elucidation of the new compounds was determined by spectroscopic methods, including 1D, 2D NMR and HR-FAB-MS. All isolated lignans were evaluated for their antineuroinflammatory effects on nitric oxide (NO) production in lipopolysaccharides (LPS)-activated murine microglia BV2 cells. Among the isolated, compounds 14 and 15 showed potent inhibitory activity against NO production (IC50 1.05 and 0.929 μM, respectively) without cell toxicity in murine microglia BV-2 cells. Compounds 11-13 and 17 also exhibited strong inhibitory effects on NO production, with IC50 values ranging from 7.07 to 15.28 μM.

  9. Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid

    PubMed Central

    Aksyuk, Anastasia A.; Newcomb, William W.; Cheng, Naiqian; Winkler, Dennis C.; Fontana, Juan; Heymann, J. Bernard

    2015-01-01

    ABSTRACT The herpes simplex virus 1 (HSV-1) capsid is a massive particle (~200 MDa; 1,250-Å diameter) with T=16 icosahedral symmetry. It initially assembles as a procapsid with ~4,000 protein subunits of 11 different kinds. The procapsid undergoes major changes in structure and composition as it matures, a process driven by proteolysis and expulsion of the internal scaffolding protein. Assembly also relies on an external scaffolding protein, the triplex, an α2β heterotrimer that coordinates neighboring capsomers in the procapsid and becomes a stabilizing clamp in the mature capsid. To investigate the mechanisms that regulate its assembly, we developed a novel isolation procedure for the metastable procapsid and collected a large set of cryo-electron microscopy data. In addition to procapsids, these preparations contain maturation intermediates, which were distinguished by classifying the images and calculating a three-dimensional reconstruction for each class. Appraisal of the procapsid structure led to a new model for assembly; in it, the protomer (assembly unit) consists of one triplex, surrounded by three major capsid protein (MCP) subunits. The model exploits the triplexes’ departure from 3-fold symmetry to explain the highly skewed MCP hexamers, the triplex orientations at each 3-fold site, and the T=16 architecture. These observations also yielded new insights into maturation. PMID:26443463

  10. A Mucosal Vaccination Approach for Herpes Simplex Virus Type-2

    PubMed Central

    Tirabassi, Rebecca S.; Ace, Christopher I.; Levchenko, Tatyana; Torchilin, Vladimir P.; Selin, Liisa K.; Nie, Siwei; Guberski, Dennis L.; Yang, Kejian

    2010-01-01

    An estimated 1 out of every 5 Americans is infected with herpes simplex virus type 2 (HSV-2). Efforts in developing a potent vaccine for HSV-2 have shown limited success. Here we describe a heterologous vaccination strategy for HSV-2 based on an intramuscular DNA prime followed by a liposome-encapsulated antigen boost delivered intranasally. Both portions of the vaccine express the immunogenic HSV-2 glycoprotein D. In female Balb/c mice, this heterologous immunisation regimen stimulated high titers of serum neutralising antibodies, a DNA priming dose dependent T helper type response, enhanced mucosal immune responses and potent protective immunity at the portal of entry for the virus: the vaginal cavity. A clear synergistic effect on immune responses and protection from infection was seen using this heterologous immunisation approach. Suboptimal DNA prime (0.5 μg) followed by the liposome boost resulted in an 80% survival rate when mice were infected 2 weeks after immunisation. A higher dose of DNA priming (5 μg) followed by the liposome boost resulted in sterilising immunity in 80% of mice. The vaccine induced durable protection in mice, demonstrated by a 60% survival rate when lethal infections were performed 20 weeks after the immunization primed with 0.5μg of DNA vaccine. PMID:21134447

  11. Position error propagation in the simplex strapdown navigation system

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The results of an analysis of the effects of deterministic error sources on position error in the simplex strapdown navigation system were documented. Improving the long term accuracy of the system was addressed in two phases: understanding and controlling the error within the system, and defining methods of damping the net system error through the use of an external reference velocity or position. Review of the flight and ground data revealed error containing the Schuler frequency as well as non-repeatable trends. The only unbounded terms are those involving gyro bias and azimuth error coupled with velocity. All forms of Schuler-periodic position error were found to be sufficiently large to require update or damping capability unless the source coefficients can be limited to values less than those used in this analysis for misalignment and gyro and accelerometer bias. The first-order effects of the deterministic error sources were determined with a simple error propagator which provided plots of error time functions in response to various source error values.

  12. Herpes simplex virus type 2 in Brazil: seroepidemiologic survey.

    PubMed

    Da Rosa-Santos, O L; Gonçalves Da Silva, A; Pereira, A C

    1996-11-01

    The incidence of genital herpes is increasing worldwide and herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcerations among sexually transmitted diseases (STDs). Findings are reported from an assessment of the prevalence of antibodies to HSV-2 in low- and high-risk populations in Brazil. 155 voluntary blood donors and 85 HIV-seropositive homosexual and promiscuous heterosexual men were screened with ELISA for infection with HSV-2 during February-August 1994. 20 highly active prostitutes were also studied during May-July 1994. The subjects were of mean age 30 years, 70% were sexually active at the time of the study, and 6.55% used condoms. Antibodies to HSV-2 were detected in 29.1% of the blood donors, 73% of the HIV-seropositive men, and 72% of the overall high-risk group. Only 10%, however, admitted to ever having episodes of genital herpes. HSV-2 infection was significantly and independently associated with years of sexual activity, history of previous STDs, number of sex partners in the previous month, number of pregnancies, number of induced abortions, and the percentage of sex acts involving receptive anal intercourse. Routine screening for HSV-2 infection should be considered in populations at high risk for STDs.

  13. GPU implementation of the simplex identification via split augmented Lagrangian

    NASA Astrophysics Data System (ADS)

    Sevilla, Jorge; Nascimento, José M. P.

    2015-10-01

    Hyperspectral imaging can be used for object detection and for discriminating between different objects based on their spectral characteristics. One of the main problems of hyperspectral data analysis is the presence of mixed pixels, due to the low spatial resolution of such images. This means that several spectrally pure signatures (endmembers) are combined into the same mixed pixel. Linear spectral unmixing follows an unsupervised approach which aims at inferring pure spectral signatures and their material fractions at each pixel of the scene. The huge data volumes acquired by such sensors put stringent requirements on processing and unmixing methods. This paper proposes an efficient implementation of a unsupervised linear unmixing method on GPUs using CUDA. The method finds the smallest simplex by solving a sequence of nonsmooth convex subproblems using variable splitting to obtain a constraint formulation, and then applying an augmented Lagrangian technique. The parallel implementation of SISAL presented in this work exploits the GPU architecture at low level, using shared memory and coalesced accesses to memory. The results herein presented indicate that the GPU implementation can significantly accelerate the method's execution over big datasets while maintaining the methods accuracy.

  14. Subcell resolution in simplex stochastic collocation for spatial discontinuities

    SciTech Connect

    Witteveen, Jeroen A.S.; Iaccarino, Gianluca

    2013-10-15

    Subcell resolution has been used in the Finite Volume Method (FVM) to obtain accurate approximations of discontinuities in the physical space. Stochastic methods are usually based on local adaptivity for resolving discontinuities in the stochastic dimensions. However, the adaptive refinement in the probability space is ineffective in the non-intrusive uncertainty quantification framework, if the stochastic discontinuity is caused by a discontinuity in the physical space with a random location. The dependence of the discontinuity location in the probability space on the spatial coordinates then results in a staircase approximation of the statistics, which leads to first-order error convergence and an underprediction of the maximum standard deviation. To avoid these problems, we introduce subcell resolution into the Simplex Stochastic Collocation (SSC) method for obtaining a truly discontinuous representation of random spatial discontinuities in the interior of the cells discretizing the probability space. The presented SSC–SR method is based on resolving the discontinuity location in the probability space explicitly as function of the spatial coordinates and extending the stochastic response surface approximations up to the predicted discontinuity location. The applications to a linear advection problem, the inviscid Burgers’ equation, a shock tube problem, and the transonic flow over the RAE 2822 airfoil show that SSC–SR resolves random spatial discontinuities with multiple stochastic and spatial dimensions accurately using a minimal number of samples.

  15. Simplex-in-cell technique for collisionless plasma simulations

    NASA Astrophysics Data System (ADS)

    Kates-Harbeck, Julian; Totorica, Samuel; Zrake, Jonathan; Abel, Tom

    2016-01-01

    We extend the simplex-in-cell (SIC) technique recently introduced in the context of collisionless dark matter fluids [1,2] to the case of collisionless plasmas. The six-dimensional phase space distribution function f (x , v) is represented by an ensemble of three-dimensional manifolds, which we refer to as sheets. The electric potential field is obtained by solving the Poisson equation on a uniform mesh, where the charge density is evaluated by a spatial projection of the phase space sheets. The SIC representation of phase space density facilitates robust, high accuracy numerical evolution of the Vlasov-Poisson system using significantly fewer tracer particles than comparable particle-in-cell (PIC) approaches by reducing the numerical shot-noise associated with the latter. We introduce the SIC formulation and describe its implementation in a new code, which we validate using standard test problems including plasma oscillations, Landau damping, and two stream instabilities in one dimension. Merits of the new scheme are shown to include higher accuracy and faster convergence rates in the number of particles. We finally motivate and outline the efficient application of SIC to higher dimensional problems.

  16. An unusual presentation of herpes simplex encephalitis with negative PCR.

    PubMed

    Buerger, Kelly J; Zerr, Kayleigh; Salazar, Richard

    2015-01-01

    A 74-year-old man presented with acute right-sided hemiparesis and epilepsia partialis continua in association with fever and confusion. Initial workup revealed possible cerebritis in the left medial frontal lobe without involvement of the temporal lobes. Cerebrospinal fluid (CSF) analysis revealed minimal lymphocytic pleocytosis but negative real-time herpes simplex virus (HSV) PCR. Acyclovir was discontinued on day 5 due to a negative infectious workup and clinical improvement. On day 9 his condition deteriorated and he was transferred to a higher level of acuity for advanced supportive care. Worsening encephalopathy and refractory status epilepticus ensued despite medical care. Repeat CSF analysis showed mild lymphocytic pleocytosis with negative real-time HSV PCR. Brain MRI revealed progression of cortical enhancement. Immunosuppressive therapy and plasma exchange were attempted without clinical response. On day 24, another lumbar puncture showed only mild lymphocytic pleocytosis. Brain MRI showed involvement of the right medial temporal lobe. Subsequently, acyclovir was resumed. The HSV-1 PCR result was positive on day 30. Unfortunately, the patient expired.

  17. Stabilising the Herpes Simplex Virus capsid by DNA packaging

    NASA Astrophysics Data System (ADS)

    Wuite, Gijs; Radtke, Kerstin; Sodeik, Beate; Roos, Wouter

    2009-03-01

    Three different types of Herpes Simplex Virus type 1 (HSV-1) nuclear capsids can be distinguished, A, B and C capsids. These capsids types are, respectively, empty, contain scaffold proteins, or hold DNA. We investigate the physical properties of these three capsids by combining biochemical and nanoindentation techniques. Atomic Force Microscopy (AFM) experiments show that A and C capsids are mechanically indistinguishable whereas B capsids already break at much lower forces. By extracting the pentamers with 2.0 M GuHCl or 6.0 M Urea we demonstrate an increased flexibility of all three capsid types. Remarkably, the breaking force of the B capsids without pentamers does not change, while the modified A and C capsids show a large drop in their breaking force to approximately the value of the B capsids. This result indicates that upon DNA packaging a structural change at or near the pentamers occurs which mechanically reinforces the capsids structure. The reported binding of proteins UL17/UL25 to the pentamers of the A and C capsids seems the most likely candidate for such capsids strengthening. Finally, the data supports the view that initiation of DNA packaging triggers the maturation of HSV-1 capsids.

  18. Anti-heparan Sulfate Peptides That Block Herpes Simplex Virus Infection in Vivo*

    PubMed Central

    Tiwari, Vaibhav; Liu, Jian; Valyi-Nagy, Tibor; Shukla, Deepak

    2011-01-01

    Heparan sulfate (HS) and its highly modified form, 3-O-sulfated heparan sulfate (3-OS HS), contribute strongly to herpes simplex virus type-1 (HSV-1) infection in vitro. Here we report results from a random M13-phage display library screening to isolate 12-mer peptides that bind specifically to HS, 3-OS HS, and block HSV-1 entry. The screening identified representative candidates from two-different groups of anti-HS peptides with high positive charge densities. Group 1, represented by G1 peptide (LRSRTKIIRIRH), belongs to a class with alternating charges (XRXRXKXXRXRX), and group 2, represented by G2 peptide (MPRRRRIRRRQK), shows repetitive charges (XXRRRRXRRRXK). Viral entry and glycoprotein D binding assays together with fluorescent microscopy data indicated that both G1 and G2 were potent in blocking HSV-1 entry into primary cultures of human corneal fibroblasts and CHO-K1 cells transiently expressing different glycoprotein D receptors. Interestingly, G2 peptide isolated against 3-OS HS displayed wider ability to inhibit entry of clinically relevant strains of HSV-1 and some divergent members of herpesvirus family including cytomegalovirus and human herpesvirus-8. To identify functional residues within G1 and G2, we performed point mutations and alanine-scanning mutagenesis. Several arginine and a lysine residues were needed for anti-HSV-1 activity, suggesting the importance of the positively charged residues in virus-cell binding and virus-induced membrane fusion. In vivo administration of G1 or G2 peptide as a prophylactic eye drop completely blocked HSV-1 spread in the mouse cornea as evident by immunohistochemistry. This result also highlights an in vivo significance of HS and 3-OS HS during ocular herpes infection. PMID:21596749

  19. Valacyclovir for the prevention of recurrent herpes simplex virus eye disease after excimer laser photokeratectomy.

    PubMed Central

    Asbell, P A

    2000-01-01

    PURPOSE: A variety of factors have been reported as inducing the reactivation of latent herpes simplex virus (HSV), among them stress, trauma, and UV radiation. Excimer laser photorefractive keratectomy (PRK) is a surgical procedure utilizing a 193 nm ultraviolet light to alter the curvature of the cornea and hence correct vision. Reactivation of ocular herpes simplex keratitis following such excimer laser PRK has been reported. All published cases of HSV reactivation following excimer laser treatment in humans are reviewed. The present study evaluates whether stress, trauma of the corneal de-epithelialization prior to the laser, or the excimer laser treatment itself to the stromal bed induces this ocular reactivation of the latent HSV, and whether a systemic antiviral agent, valacyclovir, would prevent such laser PRK-induced reactivation of the HSV. METHODS: Forty-three normal 1.5- to 2.5-kg New Zealand white rabbits were infected on the surface of the cornea with HSV-1, strain RE. The animals were monitored until resolution, and then all animals were divided into 5 treatment groups: (1) de-epithelialization only, intraperitoneal (i.p.) saline for 14 days; (2) de-epithelialization plus laser, i.p. saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day i.p. for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day i.p. for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day i.p. for 14 days. Animals were evaluated in a masked fashion by clinical examination biweekly and viral cultures biweekly through day 28. RESULTS: The reactivation rates were as follows: group 1, 0%; group 2, 67%; group 3, 50%; group 4, 17%; and group 5, 0%. Viral titers were negative in animals that had no reactivation but persistently positive in those that had reactivation (day 6 through day 28). CONCLUSIONS: Excimer laser (193 nm) treatment can trigger reactivation of ocular herpes disease (67%) and viral

  20. The Challenges and Opportunities for Development of a T-Cell Epitope-Based Herpes Simplex Vaccine

    PubMed Central

    Kuo, Tiffany; Wang, Christine; Badakhshan, Tina; Chilukuri, Sravya; BenMohamed, Lbachir

    2014-01-01

    The infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a half billion individuals worldwide. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. HSV-1 infections are more prevalent than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. While genital herpes in mainly caused by HSV-2 infections, in recent years, there is an increase in the proportion of genital herpes caused by HSV-1 infections in young adults, which reach 50% in some western societies. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries their development has been notoriously difficult. During the most recent National Institute of Health (NIH) workshop titled "Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities", basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One “common denominator” among previously failed clinical herpes vaccine trials is that they either used a whole virus or whole viral proteins, which contain both pathogenic “symptomatic” and protective “asymptomatic” antigens/epitopes. In this report, we continue to advocate that using an “asymptomatic” epitope-based vaccine strategy that selectively incorporates protective epitopes which: (i) are exclusively recognized, in vitro, by effector memory CD4+ and CD8+ TEM cells from “naturally” protected seropositive asymptomatic individuals; and (ii) protect, in vivo, human leukocyte antigen (HLA) transgenic animal models from ocular and genital herpes infections and diseases, could be the answer to many of the scientific challenges facing HSV vaccine

  1. Action of different monoterpenic compounds against Anisakis simplex s.l. L3 larvae.

    PubMed

    Hierro, I; Valero, A; Pérez, P; González, P; Cabo, M M; Montilla, M P; Navarro, M C

    2004-01-01

    Different natural monoterpenes (geraniol, citronellol, citral, carvacrol, cuminaldehyde and eugenol) are studied in vitro against Anisakis simplex s.l. L3 larvae, employing perillaldehyde as a reference substance. Final concentrations used were: 12.50, 6.25 and 3.12 microg/ml for each of the tested products. The parameters average survival, survival 50 and maximum survival were determined at 4, 8, 24 and 48 hours after the start of the experiment. All tested products, except eugenol, were active at the highest concentration (12.50 microg/ml). The damage caused to A. simplex s.l. L3 was by examining histological sections. The antioxidant activity of the tested products by DPPH free radical scavenging does not appear to be associated with their larvicide activity against A. simplex s.l. L3.

  2. Chronic active destructive herpes simplex encephalitis with recovery of viral DNA 12 years after disease onset.

    PubMed

    Asenbauer, B; McEntagart, M; King, M D; Gallagher, P; Burke, M; Farrell, M A

    1998-06-01

    Acute herpes simplex encephalitis (HSE) carries significant morbidity and mortality even after early treatment with antiviral agents (7). As well as causing acute neurological disease, Herpes viruses are associated with relapsing--remitting (Varicella--Zoster, Epstein-Barr) and chronic (Rasmussen encephalitis) disease processes (1). A two-year-old girl developed acute HSE which was followed by a 10-year neurologic illness characterised by asymmetric spastic tetraparesis, pseudobulbar palsy, the opercular syndrome of Foix-Chavany-Marie (4) and seizures. The neurological signs remained static until the child died suddenly 12 years after disease onset. Neuropathologic examination demonstrated active chronic encephalitis. Herpes simplex virus (HSV) DNA was recovered from formalin-fixed paraffin-embedded brain tissue. This case provides additional evidence for the development of chronic neurological disease attributable to persistence of herpes simplex virus type 1. PMID:9706620

  3. Herpes simplex encephalitis in Iceland 1987-2011.

    PubMed

    Dagsdóttir, Heiður Mist; Sigurðardóttir, Bryndís; Gottfreðsson, Magnús; Kristjánsson, Már; Löve, Arthur; Baldvinsdóttir, Guðrún Erna; Guðmundsson, Sigurður

    2014-01-01

    Herpes simplex encephalitis (HSE) is a serious disease with 10-20% mortality and high rate of neuropsychiatric sequelae. This study is a long-term, nationwide study in a single country, Iceland. Clinical data were obtained from patient records and from DNA PCR and antibody assays of CSF. Diagnosis of HSE was classified as definite, possible or rejected based on symptoms, as well as virological, laboratory and brain imaging criteria. A total of 30 definite cases of HSE were identified during the 25 year period 1987-2011 corresponding to incidence of 4.3 cases/106 inhabitants/year. Males were 57% of all patients, median age 50 years (range, 0-85). Fever (97%), cognitive deficits (79%), impaired consciousness (79% with GCS < 13), headache (55%) and seizures (55%) were the most common symptoms. Brain lesions were found in 24 patients (80%) by MRI or CT. All patients received intravenous acyclovir for a mean duration of 20 days. Three patients (10%) died within one year and 21/28 pts (75%) had a Karnofsky performance score of <70% with memory loss (59%), dysphasia (44%), frontal symptoms (44%) and seizures (30%) as the most frequent sequelae. Mean delay from onset of symptoms to treatment was 6 days; this was associated with adverse outcome. In conclusion, the incidence of `HSE is higher than recently reported in a national registry study from Sweden. Despite advances in rapid diagnosis and availability of treatment of HSE, approximately three of every four patients die or are left with serious neurological impairment. PMID:25279315

  4. Herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome.

    PubMed

    Chrétien, F; Bélec, L; Hilton, D A; Flament-Saillour, M; Guillon, F; Wingertsmann, L; Baudrimont, M; de Truchis, P; Keohane, C; Vital, C; Love, S; Gray, F

    1996-10-01

    Herpes simplex (HSV) infection of the central nervous system is uncommon in AIDS and usually has an atypical topography. This review is centred around the case of a 49-year-old homosexual patient with AIDS who died from diffuse encephalopathy. Neuropathological examination revealed necrotic and haemorrhagic changes involving both temporal lobes, insulae and cingulate gyri. Cowdry type A intranuclear inclusion bodies were abundant but inflammation was minimal. Electron microscopy confirmed characteristic herpes virus particles. Immunocyto-chemistry was positive for HSV type 1 and 2. In situ hybridization and PCR, however, were positive for HSV type 1 but excluded HSV type 2. There was associated cytomegalovirus ventriculitis but clearly separated from HSV encephalitis. There were no histological features of HIV encephalitis and HIV could not be demonstrated by immunocytochemistry or by PCR to demonstrate proviral DNA. Apoptotic neurons were numerous in areas with a severe macrophage reaction. Only two pathological cases with characteristic limbic distribution and necrotic haemorrhagic histologic have been reported previously. The rarity of these reports suggests that in advanced AIDS, the immune reaction causing a typical necrotizing encephalitis cannot be mounted. Distinction between HSV type 1 and 2 infection may be difficult by immunocytochemistry and usually requires in situ hybridization, tissue culture or PCR. In AIDS patients, HSV-1 has been identified as responsible for encephalitis whereas HSV-2 has been more responsible for myelitis. Associated productive HIV infection of the CNS was found in none of the cases. In contrast, cytomegalovirus encephalitis was found in nine of 11 cases of AIDS-associated HSV encephalitis. PMID:8930949

  5. Purification and structural characterization of herpes simplex virus glycoprotein C

    SciTech Connect

    Kikuchi, G.E.; Baker, S.A.; Merajver, S.D.; Coligan, J.E.; Levine, M.; Glorioso, J.C.; Nairn, R.

    1987-01-27

    Purification of herpes simplex virus glycoprotein C (gC) in microgram amounts yielded sufficient material for an analysis of its secondary structure. Purification was facilitated by using the mutant virus gC-3, which bears a point mutation that interrupts the putative hydrophobic membrane anchor sequence, causing the secretion of gC-3 protein into the cell culture medium. gC-3 protein was purified by size fractionation of concentrated culture medium from infected cells on a gel filtration column of Sephacryl S-200, followed by immunoaffinity chromatography on a column constructed of gC-specific monoclonal antibodies cross-linked to a protein A-Sepharose CL-4B matrix. Purified gC-3 had a molecular weight of 130,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the size expected for gC, was reactive with gC-specific monoclonal antibodies in protein immunoblots, and contained amino acid sequences characteristic of gC as determined by radiochemical amino acid microsequence analyses. Polyclonal antisera obtained from a rabbit immunized with gC-3 reacted with wild-type gC in immunoprecipitation, enzyme immunoassay, and immunoelectroblot (western blot) assays. Deglycosylation by treatment with trifluoromethanesulfonic acid reduced the molecular weight of gC-3 by approximately 35%. Analyses of both native and deglycosylated gC-3 by Raman spectroscopy showed that the native molecule consists of about 17%..cap alpha..-helix, 24% ..beta..-sheet, and 60% disordered secondary structures, whereas deglycosylated gC-3 consists of about 8% ..cap alpha..-helix, 10% ..beta..-sheet, 81% disordered structures. These data were in good agreement with the 11% ..cap alpha..-helix, 18% ..beta..-sheet, 61% ..beta..-turn, and 9% disordered structures calculated from Chou-Fasman analysis of the primary sequence of gC-3.

  6. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

    PubMed Central

    Kennedy, Peter G. E.; Rovnak, Joel; Badani, Hussain

    2015-01-01

    Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, a third of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection. Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unravelled. In both cases latent viral DNA exists in an ‘end-less’ state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary latency associated transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection as early-stage virus reactivation may have transpired in the post-mortem time period in the ganglia. Nonetheless, low-level transcription of VZV ORF63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is

  7. Optimization and comparison of three vacuum mixing systems for porosity reduction of Simplex P cement.

    PubMed

    Davies, J P; Harris, W H

    1990-05-01

    Simplex P bone cement was prepared in three commercially available vacuum mixing systems, the Enhancement Mixer, the Mixevac II High Vacuum System, and the Mitab Vacuum System, to determine the improvement in fatigue strength associated with porosity reduction of the cement in all three systems. The results of the fatigue tests of vacuum-mixed Simplex P were also compared to the fatigue strength of Simplex P prepared by centrifugation of the cement immediately after mixing. Vacuum mixing one pack of Simplex P per syringe in all three systems was not effective in complete removal of all the large voids from the cement. Fatigue failure occurred very early in those specimens containing the large voids. There was no significant difference in fatigue life between one pack of cement per syringe mixed under vacuum in the three systems and the control cement (no vacuum, uncentrifuged). Vacuum mixing two packs of cement per syringe was more effective than one pack per syringe, and all three systems significantly increased the cycles to failure of Simplex P over the control cement. However, the Enhancement and Mitab vacuum mixing systems still produced some very weak specimens in fatigue. Two packs of cement per syringe prepared in the Mixevac II vacuum mixing system were significantly stronger in fatigue than two packs mixed in either the Enhancement or Mitab vacuum system. The Mixevac II vacuum mixing system was the most effective technique of the three vacuum mixing systems tested. Centrifugation of one or two packs of Simplex P per syringe produced a more uniform cement that was free of large voids and thus eliminated the very weak specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2323141

  8. Recurrent meningitis attributable to herpes simplex virus-2 in a child.

    PubMed

    Moustaki, Maria; Sharifi, Fariba; Stasinopoulou, Anastasia; Fretzayas, Andrew; Karpathios, Themistocles

    2010-05-01

    A boy manifested episodes of recurrent meningitis that were attributed to herpes simplex virus-2 infection. He presented no concurrent or previous history of involvement of the genitourinary system. He exhibited headaches, dizziness, photophobia, loss of balance, and vomiting. He underwent three episodes of aseptic meningitis. The herpes simplex virus-2 etiology was confirmed by polymerase chain reaction of the cerebrospinal fluid in the last two episodes. After the third occurrence, he was treated with acyclovir. Five years have elapsed since then, without the recurrence of aseptic meningitis.

  9. Simplex didactics: A non-linear trajectory for research in education.

    PubMed

    Sibilio, Maurizio

    2015-12-01

    The concept of simplexity, as proposed by Alain Berthoz, is based on the assumption that solutions elaborated by living organisms to decipher and face complexity could be applicable to all complex adaptive systems. Within the pedagogical and didactic context the proposal of the French physiologist could provide a scientific research trajectory aiming at solving the tension between theory, praxis, descriptive approaches and practical needs. Thus, simplexity seems to be an operational strategy based on the identification of the principles that rule and guide the didactic action through patterns of adaptation, which allow to decipher complexity in terms of data elaboration and decision making among different opportunities.

  10. Simplex didactics: A non-linear trajectory for research in education.

    PubMed

    Sibilio, Maurizio

    2015-12-01

    The concept of simplexity, as proposed by Alain Berthoz, is based on the assumption that solutions elaborated by living organisms to decipher and face complexity could be applicable to all complex adaptive systems. Within the pedagogical and didactic context the proposal of the French physiologist could provide a scientific research trajectory aiming at solving the tension between theory, praxis, descriptive approaches and practical needs. Thus, simplexity seems to be an operational strategy based on the identification of the principles that rule and guide the didactic action through patterns of adaptation, which allow to decipher complexity in terms of data elaboration and decision making among different opportunities. PMID:26746648

  11. Complete Cytolysis and Neonatal Lethality in Keratin 5 Knockout Mice Reveal Its Fundamental Role in Skin Integrity and in Epidermolysis Bullosa Simplex

    PubMed Central

    Peters, Bettina; Kirfel, Jutta; Büssow, Heinrich; Vidal, Miguel; Magin, Thomas M.

    2001-01-01

    In human patients, a wide range of mutations in keratin (K) 5 or K14 lead to the blistering skin disorder epidermolysis bullosa simplex. Given that K14 deficiency does not lead to the ablation of a basal cell cytoskeleton because of a compensatory role of K15, we have investigated the requirement for the keratin cytoskeleton in basal cells by inactivating the K5 gene in mice. We report that the K5−/− mice die shortly after birth, lack keratin filaments in the basal epidermis, and are more severely affected than K14−/− mice. In contrast to the K14−/− mice, we detected a strong induction of the wound-healing keratin K6 in the suprabasal epidermis of cytolyzed areas of postnatal K5−/− mice. In addition, K5 and K14 mice differed with respect to tongue lesions. Moreover, we show that in the absence of K5 and other type II keratins, residual K14 and K15 aggregated along hemidesmosomes, demonstrating that individual keratins without a partner are stable in vivo. Our data indicate that K5 may be the natural partner of K15 and K17. We suggest that K5 null mutations may be lethal in human epidermolysis bullosa simplex patients. PMID:11408584

  12. Presence of Anisakis simplex (Rudolphi, 1809 det. Krabbe, 1878) and Hysterothylacium aduncum (Rudolphi, 1802) (Nematoda; Anisakidae) in runts of farmed Atlantic salmon, Salmo salar L.

    PubMed

    Mo, T A; Gahr, A; Hansen, H; Hoel, E; Oaland, Ø; Poppe, T T

    2014-02-01

    One hundred farmed Atlantic salmon, Salmo salar L., were examined for the presence of nematodes by digestion of tissue in HCl-pepsin solution. All fish were sampled from one cage in a fish farm on the Norwegian south-west coast. Fifty harvest quality salmon, that is, salmon for human consumption (mean 5.4 kg, variation 3.0-7.6 kg), were sampled at the processing line while 50 salmon runts (mean 1.1 kg, variation 0.4-1.8 kg), discarded due to poor performance, were sampled from the discard bin after the grading station. Runts are individual fish with clear signs of poor performance over time and abnormal appearance and are thus not processed for human consumption. No nematodes were found in the musculature or viscera of the 50 harvest quality salmon. In total, 75 nematodes were found in 10 (20%) of the runts; 53 nematodes in the viscera and 22 in the musculature. Nematodes in the musculature were identified as Anisakis simplex (Rudolphi, 1809 det. Krabbe, 1878), while nematodes in the viscera were identified as A. simplex and Hysterothylacium aduncum (Rudolphi, 1802). PMID:23488892

  13. Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy

    PubMed Central

    Ning, Jianfang; Wakimoto, Hiroaki

    2014-01-01

    Oncolytic viruses (OV) are a class of antitumor agents that selectively kill tumor cells while sparing normal cells. Oncolytic herpes simplex virus (oHSV) has been investigated in clinical trials for patients with the malignant brain tumor glioblastoma for more than a decade. These clinical studies have shown the safety of oHSV administration to the human brain, however, therapeutic efficacy of oHSV as a single treatment remains unsatisfactory. Factors that could hamper the anti-glioblastoma efficacy of oHSV include: attenuated potency of oHSV due to deletion or mutation of viral genes involved in virulence, restricting viral replication and spread within the tumor; suboptimal oHSV delivery associated with intratumoral injection; virus infection-induced inflammatory and cellular immune responses which could inhibit oHSV replication and promote its clearance; lack of effective incorporation of oHSV into standard-of-care, and poor knowledge about the ability of oHSV to target glioblastoma stem cells (GSCs). In an attempt to address these issues, recent research efforts have been directed at: (1) design of new engineered viruses to enhance potency, (2) better understanding of the role of the cellular immunity elicited by oHSV infection of tumors, (3) combinatorial strategies with different antitumor agents with a mechanistic rationale, (4) “armed” viruses expressing therapeutic transgenes, (5) use of GSC-derived models in oHSV evaluation, and (6) combinations of these. In this review, we will describe the current status of oHSV clinical trials for glioblastoma, and discuss recent research advances and future directions toward successful oHSV-based therapy of glioblastoma. PMID:24999342

  14. Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors

    PubMed Central

    Parker, Jacqueline N.; Gillespie, G. Yancey; Love, Cammy E.; Randall, Suzanne; Whitley, Richard J.; Markert, James M.

    2000-01-01

    Genetically engineered, neuroattenuated herpes simplex viruses (HSVs) expressing various cytokines can improve survival when used in the treatment of experimental brain tumors. These attenuated viruses have both copies of γ134.5 deleted. Recently, we demonstrated increased survival of C57BL/6 mice bearing syngeneic GL-261 gliomas when treated with an engineered HSV expressing IL-4, as compared with treatment with the parent construct (γ134.5−) alone or with a virus expressing IL-10. Herein, we report construction of a conditionally replication-competent mutant expressing both subunits of mIL-12 (M002) and its evaluation in a syngeneic neuroblastoma murine model. IL-12 induces a helper T cell subset type 1 response, which may induce more durable antitumor effects. In vitro studies showed that, when infected with M002, both Vero cells and murine Neuro-2a neuroblastoma cells produced physiologically relevant levels of IL-12 heterodimers, as determined by ELISA. M002 was cytotoxic for Neuro-2a cells and human glioma cell lines U251MG and D54MG. Neurotoxicity studies, as defined by plaque-forming units/LD50, performed in HSV-1-sensitive A/J strain mice found that M002 was not toxic even at high doses. When evaluated in an intracranial syngeneic neuroblastoma murine model, median survival of M002-treated animals was significantly longer than the median survival of animals treated with R3659, the parent γ134.5− mutant lacking any cytokine gene insert. Immunohistochemical analysis of M002-treated tumors identified a pronounced influx of CD4+ T cells and macrophages as well as CD8+ cells when compared with an analysis of R3659-treated tumors. We conclude that M002 produced a survival benefit via oncolytic effects combined with immunologic effects meditated by helper T cells of subset type 1. PMID:10681459

  15. Effect of black tea extract on herpes simplex virus-1 infection of cultured cells

    PubMed Central

    2013-01-01

    Background The purpose of this investigation was to determine if black tea extract (BTE), consisting primarily of flavanol compounds called theaflavins, could inhibit herpes simplex virus type-1 (HSV-1) infection in cultured A549 (human epithelial) and Vero cells. Methods The effect of BTE both on A549 and Vero cultured cells and on HSV-1 was assessed by using phase contrast and fluorescent microscopy, and cell viability and proliferation assays. After establishing the maximum non-cytotoxic concentration of BTE, A549 and Vero cells and HSV-1 virions were treated with varying concentrations of BTE, respectively. A549 and Vero cells were infected with HSV-1 with green fluorescent protein (GFP) insert at the UL46 gene. The effect of infectivity was determined by viral DNA extraction followed by PCR, plaque assays, adsorption assays, and electrophoresis of PCR products. Results BTE was not cytotoxic to A549 and Vero cells, as confirmed by cell viability and proliferation assays, in which BTE treated groups paralleled the positive control group. For both cell lines, plaque assays and fluorescent microscopy indicated an inverse relationship between BTE concentration (from 0.14 μM – 1.4 mM) and HSV-1 infectivity. Specifically, PCR and electrophoresis showed a reduction in the viral genome following treatment with BTE. In addition, there was a noticeable decrease in the amount of viral plaques for BTE treated samples in the adsorption assays. Conclusions BTE consisting primarily of theaflavins is not cytotoxic and can reduce or block the production of infectious HSV-1 virions in cultured A549 and Vero cells, thus inhibiting the infectivity of the virus by interfering in the attachment, penetration and viral DNA replication of HSV-1 particles. These findings indicate that BTE enriched with theaflavins has the potential to be developed as a safe, therapeutic antiviral agent to prevent the spread of HSV-1. PMID:23777309

  16. Herpes simplex virus type 1 and Bell's palsy-a current assessment of the controversy.

    PubMed

    Kennedy, Peter Ge

    2010-02-01

    Bell's palsy causes about two thirds of cases of acute peripheral facial weakness. Although the majority of cases completely recover spontaneously, about 30% of cases do not and are at risk from persisting severe facial paralysis and pain. It has been suggested that herpes simplex virus type 1 (HSV-1) may be the etiological agent that causes Bell's palsy. Although corticosteroid therapy is now universally recognized as improving the outcome of Bell's palsy, the question as to whether or not a combination of antiviral agents and corticosteroids result in a better rate of complete facial recovery compared with corticosteroids alone is now a highly contentious issue. The evidence obtained from laboratory studies of animals and humans that HSV-1 may be linked to facial nerve paralysis is first outlined. The discussion then focuses on the results of different clinical trials of the efficacy of antiviral agents combined with corticosteroids in increasing the rate of complete recovery in Bell's palsy. These have often given different results leading to opposite conclusions as to the efficacy of antivirals. Of three recent meta-analyses of previous trials, two concluded that antivirals produce no added benefit to corticosteroids alone in producing complete facial recovery, and one concluded that such combined therapy may be associated with additional benefit. Although it is probably not justified at the present time to treat patients with Bell's palsy with antiviral agents in addition to corticosteroids, it remains to be shown whether antivirals may be beneficial in treating patients who present with severe or complete facial paralysis.

  17. Critical role of microRNA-155 in herpes simplex encephalitis.

    PubMed

    Bhela, Siddheshvar; Mulik, Sachin; Reddy, Pradeep B J; Richardson, Raphael L; Gimenez, Fernanda; Rajasagi, Naveen K; Veiga-Parga, Tamara; Osmand, Alexander P; Rouse, Barry T

    2014-03-15

    HSV infection of adult humans occasionally results in life-threatening herpes simplex encephalitis (HSE) for reasons that remain to be defined. An animal system that could prove useful to model HSE could be microRNA-155 knockout (miR-155KO) mice. Thus, we observe that mice with a deficiency of miR-155 are highly susceptible to HSE with a majority of animals (75-80%) experiencing development of HSE after ocular infection with HSV-1. The lesions appeared to primarily represent the destructive consequences of viral replication, and animals could be protected from HSE by acyclovir treatment provided 4 d after ocular infection. The miR-155KO animals were also more susceptible to development of zosteriform lesions, a reflection of viral replication and dissemination within the nervous system. One explanation for the heightened susceptibility to HSE and zosteriform lesions could be because miR-155KO animals develop diminished CD8 T cell responses when the numbers, functionality, and homing capacity of effector CD8 T cell responses were compared. Indeed, adoptive transfer of HSV-immune CD8 T cells to infected miR-155KO mice at 24 h postinfection provided protection from HSE. Deficiencies in CD8 T cell numbers and function also explained the observation that miR-155KO animals were less able than control animals to maintain HSV latency. To our knowledge, our observations may be the first to link miR-155 expression with increased susceptibility of the nervous system to virus infection.

  18. Downstream effects of plectin mutations in epidermolysis bullosa simplex with muscular dystrophy.

    PubMed

    Winter, Lilli; Türk, Matthias; Harter, Patrick N; Mittelbronn, Michel; Kornblum, Cornelia; Norwood, Fiona; Jungbluth, Heinz; Thiel, Christian T; Schlötzer-Schrehardt, Ursula; Schröder, Rolf

    2016-01-01

    Mutations of the human plectin gene (PLEC) on chromosome 8q24 cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). In the present study we analyzed the downstream effects of PLEC mutations on plectin protein expression and localization, the structure of the extrasarcomeric desmin cytoskeleton, protein aggregate formation and mitochondrial distribution in skeletal muscle tissue from three EBS-MD patients. PLEC gene analysis in a not previously reported 35-year-old EBS-MD patient with additional disease features of cardiomyopathy and malignant arrhythmias revealed novel compound heterozygous (p.(Phe755del) and p.(Lys1040Argfs*139)) mutations resulting in complete abolition of plectin protein expression. In contrast, the other two patients with different homozygous PLEC mutations showed preserved plectin protein expression with one only expressing rodless plectin variants, and the other markedly reduced protein levels. Analysis of skeletal muscle tissue from all three patients revealed severe disruption of the extrasarcomeric intermediate filament cytoskeleton, protein aggregates positive for desmin, syncoilin, and synemin, degenerative myofibrillar changes, and mitochondrial abnormalities comprising respiratory chain dysfunction and an altered organelle distribution and amount.Our study demonstrates that EBS-MD causing PLEC mutations universally result in a desmin protein aggregate myopathy phenotype despite marked differences in individual plectin protein expression patterns. Since plectin is the key cytolinker protein that regulates the structural and functional organization of desmin filaments, the defective anchorage and spacing of assembled desmin filaments is the key pathogenetic event that triggers the formation of desmin protein aggregates as well as secondary mitochondrial pathology. PMID:27121971

  19. A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome

    SciTech Connect

    Heilbronn, R.; zur Hausen, H. )

    1989-09-01

    Herpes simplex virus (HSV) induces DNA amplification of target genes within the host cell chromosome. To characterize the HSV genes that mediate the amplification effect, combinations of cloned DNA fragments covering the entire HSV genome were transiently transfected into simian virus 40 (SV40)-transformed hamster cells. This led to amplification of the integrated SV40 DNA sequences to a degree comparable to that observed after transfection of intact virion DNA. Transfection of combinations of subclones and of human cytomegalovirus immediate-early promoter-driven expression constructs for individual open reading frames led to the identification of sic HSV genes which together were necessary and sufficient for the induction of DNA amplification: UL30 (DNA polymerase), UL29 (major DNA-binding protein), UL5, UL8, UL42, and UL52. All of these genes encode proteins necessary for HSV DNA replication. However, an additional gene coding for an HSV origin-binding protein (UL9) was required for origin-dependent HSV DNA replication but was dispensable for SV40 DNA amplification. The results show that a subset of HSV replication genes is sufficient for the induction of DNA amplification. This opens the possibility that HSV expresses functions sufficient for DNA amplification but separate from those responsible for lytic viral growth. HSV infection may thereby induce DNA amplification within the host cell genome without killing the host by lytic viral growth. This may lead to persistence of a cell with a new genetic phenotype, which would have implications for the pathogenicity of the virus in vivo.

  20. Prophylactic and Therapeutic Modulation of Innate and Adaptive Immunity Against Mucosal Infection of Herpes Simplex Virus

    PubMed Central

    Uyangaa, Erdenebileg; Patil, Ajit Mahadev

    2014-01-01

    Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are the most common cause of genital ulceration in humans worldwide. Typically, HSV-1 and 2 infections via mucosal route result in a lifelong latent infection after peripheral replication in mucosal tissues, thereby providing potential transmission to neighbor hosts in response to reactivation. To break the transmission cycle, immunoprophylactics and therapeutic strategies must be focused on prevention of infection or reduction of infectivity at mucosal sites. Currently, our understanding of the immune responses against mucosal infection of HSV remains intricate and involves a balance between innate signaling pathways and the adaptive immune responses. Numerous studies have demonstrated that HSV mucosal infection induces type I interferons (IFN) via recognition of Toll-like receptors (TLRs) and activates multiple immune cell populations, including NK cells, conventional dendritic cells (DCs), and plasmacytoid DCs. This innate immune response is required not only for the early control of viral replication at mucosal sites, but also for establishing adaptive immune responses against HSV antigens. Although the contribution of humoral immune response is controversial, CD4+ Th1 T cells producing IFN-γ are believed to play an important role in eradicating virus from the hosts. In addition, the recent experimental successes of immunoprophylactic and therapeutic compounds that enhance resistance and/or reduce viral burden at mucosal sites have accumulated. This review focuses on attempts to modulate innate and adaptive immunity against HSV mucosal infection for the development of prophylactic and therapeutic strategies. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses. Thus, we summarized the current evidence of various immune mediators in response to mucosal HSV infection, focusing on the importance of innate immune responses. PMID:25177251

  1. Efficacy Results of a Trial of a Herpes Simplex Vaccine

    PubMed Central

    Belshe, Robert B.; Leone, Peter A.; Bernstein, David I.; Wald, Anna; Levin, Myron J.; Stapleton, Jack T.; Gorfinkel, Iris; Morrow, Rhoda L. Ashley; Ewell, Marian G.; Stokes-Riner, Abbie; Dubin, Gary; Heineman, Thomas C.; Schulte, Joann M.; Deal, Carolyn D.

    2012-01-01

    Background Two previous studies of a herpes simplex virus type 2 (HSV-2) subunit vaccine containing glycoprotein D in HSV-discordant couples revealed 73% and 74% efficacy against genital disease in women who were negative for both HSV type 1 (HSV-1) and HSV-2 antibodies. Efficacy was not observed in men or HSV-1 seropositive women. Methods We conducted a randomized, double-blind efficacy field trial involving 8323 women 18 to 30 years of age who were negative for antibodies to HSV-1 and HSV-2. At months 0, 1, and 6, some subjects received the investigational vaccine, consisting of 20 μg of glycoprotein D from HSV-2 with alum and 3-O-deacylated monophosphoryl lipid A as an adjuvant; control subjects received the hepatitis A vaccine, at a dose of 720 enzyme-linked immunosorbent assay (ELISA) units. The primary end point was occurrence of genital herpes disease due to either HSV-1 or HSV-2 from month 2 (1 month after dose 2) through month 20. Results The HSV vaccine was associated with an increased risk of local reactions as compared with the control vaccine, and it elicited ELISA and neutralizing antibodies to HSV-2. Overall, the vaccine was not efficacious; vaccine efficacy was 20% (95% confidence interval [CI], −29 to 50) against genital herpes disease. However, efficacy against HSV-1 genital disease was 58% (95% CI, 12 to 80). Vaccine efficacy against HSV-1 infection (with or without disease) was 35% (95% CI, 13 to 52), but efficacy against HSV-2 infection was not observed (−8%; 95% CI, −59 to 26). Conclusions In a study population that was representative of the general population of HSV-1– and HSV-2–seronegative women, the investigational vaccine was effective in preventing HSV-1 genital disease and infection but not in preventing HSV-2 disease or infection. (Funded by the National Institute of Allergy and Infectious Diseases and GlaxoSmithKline; ClinicalTrials.gov number, NCT00057330.) PMID:22216840

  2. Candidate topical microbicides bind herpes simplex virus glycoprotein B and prevent viral entry and cell-to-cell spread.

    PubMed

    Cheshenko, Natalia; Keller, Marla J; MasCasullo, Veronica; Jarvis, Gary A; Cheng, Hui; John, Minnie; Li, Jin-Hua; Hogarty, Kathleen; Anderson, Robert A; Waller, Donald P; Zaneveld, Lourens J D; Profy, Albert T; Klotman, Mary E; Herold, Betsy C

    2004-06-01

    Topical microbicides designed to prevent acquisition of sexually transmitted infections are urgently needed. Nonoxynol-9, the only commercially available spermicide, damages epithelium and may enhance human immunodeficiency virus transmission. The observation that herpes simplex virus (HSV) and human immunodeficiency virus bind heparan sulfate provided the rationale for the development of sulfated or sulfonated polymers as topical agents. Although several of the polymers have advanced to clinical trials, the spectrum and mechanism of anti-HSV activity and the effects on soluble mediators of inflammation have not been evaluated. The present studies address these gaps. The results indicate that PRO 2000, polystyrene sulfonate, cellulose sulfate, and polymethylenehydroquinone sulfonate inhibit HSV infection 10,000-fold and are active against clinical isolates, including an acyclovir-resistant variant. The compounds formed stable complexes with glycoprotein B and inhibit viral binding, entry, and cell-to-cell spread. The effects may be long lasting due to the high affinity and stability of the sulfated compound-virus complex, as evidenced by surface plasmon resonance studies. The candidate microbicides retained their antiviral activities in the presence of cervical secretions and over a broad pH range. There was little reduction in cell viability following repeated exposure of human endocervical cells to these compounds, although a reduction in secretory leukocyte protease inhibitor levels was observed. These studies support further development and rigorous evaluation of these candidate microbicides. PMID:15155195

  3. Inhibition of nucleoside transport and synergistic potentiation of methotrexate cytotoxicity by cimicifugoside, a triterpenoid from Cimicifuga simplex.

    PubMed

    Yawata, Ayako; Matsuhashi, Yuko; Kato, Hanako; Uemura, Keiko; Kusano, Genjiro; Ito, Junko; Chikuma, Toshiyuki; Hojo, Hiroshi

    2009-11-01

    Cimicifugoside, a triterpenoid isolated from Cimicifuga simplex, which has been used as a traditional Chinese medicine due to its anti-inflammatory, analgesic or anti-pyretic action, was examined for inhibition of nucleoside transport and synergistic potentiation of methotrexate cytotoxicity. Cimicifugoside inhibited uptake of uridine, thymidine and adenosine in human leukemia U937 cells with the low nanomolar IC(50) values, but did not affect that of uracil, leucine or 2-deoxyglucose at cimicifugenin (aglycon of cimicifugoside)>bugbanoside B>cimicifugenin A, O-methyl cimicifugenin and bugbanoside A. Cimicifugoside had less affinity for the binding site of nitrobenzylthioinosine (typical high-affinity inhibitor of equilibrative nucleoside transporter-1) in U937 cells, K562 cells and human erythrocyte membranes compared with the prototype nucleoside transport inhibitor dipyridamole. Cimicifugoside markedly potentiated methotrexate cytotoxicity in a culture of U937 cells and human carcinoma KB cells. Potentiation of methotrexate cytotoxicity by cimicifugoside analogs in U937 cells was in proportion to their inhibitory activity against uridine uptake. The present study demonstrates that cimicifugoside is a novel specific nucleoside transport inhibitor that displays synergistic potentiation of methotrexate cytotoxicity. PMID:19748575

  4. Non-nucleosidic inhibition of Herpes simplex virus DNA polymerase: mechanistic insights into the anti-herpetic mode of action of herbal drug withaferin A

    PubMed Central

    2011-01-01

    Background Herpes Simplex Virus 1 and 2 causes several infections in humans including cold sores and encephalitis. Previous antiviral studies on herpes viruses have focussed on developing nucleoside analogues that can inhibit viral polymerase and terminate the replicating viral DNA. However, these drugs bear an intrinsic non-specificity as they can also inhibit cellular polymerase apart from the viral one. The present study is an attempt to elucidate the action mechanism of naturally occurring withaferin A in inhibiting viral DNA polymerase, thus providing an evidence for its development as a novel anti-herpetic drug. Results Withaferin A was found to bind very similarly to that of the previously reported 4-oxo-DHQ inhibitor. Withaferin A was observed binding to the residues Gln 617, Gln 618, Asn 815 and Tyr 818, all of which are crucial to the proper functioning of the polymerase. A comparison of the conformation obtained from docking and the molecular dynamics simulations shows that substantial changes in the binding conformations have occurred. These results indicate that the initial receptor-ligand interaction observed after docking can be limited due to the receptor rigid docking algorithm and that the conformations and interactions observed after simulation runs are more energetically favoured. Conclusions We have performed docking and molecular dynamics simulation studies to elucidate the binding mechanism of prospective herbal drug withaferin A onto the structure of DNA polymerase of Herpes simplex virus. Our docking simulations results give high binding affinity of the ligand to the receptor. Long de novo MD simulations for 10 ns performed allowed us to evaluate the dynamic behaviour of the system studied and corroborate the docking results, as well as identify key residues in the enzyme-inhibitor interactions. The present MD simulations support the hypothesis that withaferin A is a potential ligand to target/inhibit DNA polymerase of the Herpes simplex

  5. The effect of adding tobramycin to Simplex P cement on femoral stem micromotion as measured by radiostereometric analysis

    PubMed Central

    2012-01-01

    Background Previous in vitro research on addition of antibiotics to bone cement has found no statistically significant deterioration in mechanical properties. However, no clinical studies have compared the performance of tobramycin-laden bone cement with that of standard bone cement (Simplex P). Patients and Methods 23 patients (25 hips) were randomized to receive an Exeter (Stryker Orthopaedics) femoral stem cemented with either Simplex P (standard) or Simplex T (tobramycin-laden) cement. There were 2 years of follow-up, with scheduled radiostereometric (RSA) examinations. Results All stems migrated distally and showed some degree of retroversion. No clinically significant differences in stem subsidence or retroversion were found between the Simplex T and Simplex P cement groups after 2 years. Overall subsidence was less than in previous studies, probably due to a postponed initial post-surgical examination. Rates of subsidence in both cement groups were consistent with those from previous studies of Exeter stems. Interpretation Subsidence of the femoral stem after 2 years was similar in the Simplex T (tobramycin-laden) and Simplex P (standard) groups. PMID:22248163

  6. Condoms do not cover everything: an unusual presentation of herpes simplex virus-2 infection.

    PubMed

    van den Bos, R R; van der Meijden, W I

    2007-04-01

    We report on a patient who presented with an unusual manifestation of primary herpes simplex virus (HSV) infection. Furthermore, this case again shows that even the correct use of a condom has limited protecting value. We emphasize the usefulness of informing patients carefully about transmission risks of HSV. PMID:17509182

  7. [Fatal fulminating hepatitis due to Herpes simplex virus type 2 in a young immunocompetent female].

    PubMed

    Chauveau, E; Martin, J; Saliba, F; Nicolas, X; Richecoeur, M; Klotz, F

    1999-01-01

    Fulminant herpes simplex viral hepatitis is uncommon in immunocompetent subjects. A 24-year-old woman presenting hepatomegaly with fever was hospitalized after returning from a trip to southern Africa. The patient was neither pregnant nor immunocompromised. Because of recent tropical travel, differential diagnosis included alphabetic hepatotropic virus infection, yellow fever, African hemorrhagic fever, and arbovirus infection. After ruling out other common viral etiologies, a definitive diagnosis of herpes simplex viral infection was made on the basis of clinical and laboratory findings showing high fever, leukopenia, and thrombopenia; of histological examination of the native liver after transplantation showing non-inflammatory confluent focal hemorrhagic necrosis; and on serologic tests demonstrating seroconversion for herpes simplex virus type 2. Outcome after transplantation was rapidly fatal but the death was not directly related to infection. The most likely etiology of fulminant hepatitis in a young woman returning from travel in a tropical area is hepatitis virus B or hepatitis virus E in cases involving pregnancy. However herpes simplex virus should be included in differential diagnosis even in immunocompetent subjects.

  8. Ficus whitefly, Singhiella simplex, and its predation by a coccinellid beetle, Delphastus catalinae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ficus whitefly, Singhiella simplex, is a pest of ficus plant such as Ficus benjamina, F. altissima, F. bengalensis and others. This invasive pest causes plants to exhibit leaf yellowing, wilting, and eventually, leaf drop. There is little information on the effectiveness of insect predators to contr...

  9. Molecular requirement for sterols in herpes simplex virus entry and infectivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Herpes simplex virus 1 (HSV-1) required cholesterol for virion-induced membrane fusion. HSV successfully entered DHCR24-/-cells, which lack a desmosterol-to-cholesterol conversion enzyme, indicating entry can occur independently of cholesterol. Depletion of desmosterol from these cells resulted in d...

  10. Serologic Screening for Herpes Simplex Virus among University Students: A Pilot Study

    ERIC Educational Resources Information Center

    Mark, Hayley; Nanda, Joy P.; Joffe, Alain; Roberts, Jessica; Rompalo, Anne; Melendez, Johan; Zenilman, Jonathan

    2008-01-01

    Objective: The authors examined the feasibility of conducting serologic testing for the herpes simplex virus 2 (HSV-2) among university students and assessed the psychosocial impact of an HSV-2 diagnosis. Methods: The authors recruited a convenience sample of 100 students (aged 18-39 years) without a history of genital herpes from 1 university…

  11. Does the Cognitive Architecture of Simplex and Multiplex ASD Families Differ?

    ERIC Educational Resources Information Center

    Oerlemans, Anoek M.; Hartman, Catharina A.; Franke, Barbara; Buitelaar, Jan K.; Rommelse, Nanda N. J.

    2016-01-01

    Children with an autism spectrum disorder (ASD) and their unaffected siblings from 54 simplex (SPX, one individual in the family affected) and 59 multiplex (MPX, two or more individuals affected) families, and 124 controls were assessed on intelligence, social cognition and executive functions. SPX and MPX ASD probands displayed similar cognitive…

  12. Population- and Family-Based Studies Associate the "MTHFR" Gene with Idiopathic Autism in Simplex Families

    ERIC Educational Resources Information Center

    Liu, Xudong; Solehdin, Fatima; Cohen, Ira L.; Gonzalez, Maripaz G.; Jenkins, Edmund C.; Lewis, M. E. Suzanne; Holden, Jeanette J. A.

    2011-01-01

    Two methylenetetrahydrofolate reductase gene ("MTHFR") functional polymorphisms were studied in 205 North American simplex (SPX) and 307 multiplex (MPX) families having one or more children with an autism spectrum disorder. Case-control comparisons revealed a significantly higher frequency of the low-activity 677T allele, higher prevalence of the…

  13. Hepatoprotective constituents of Firmiana simplex stem bark against ethanol insult to primary rat hepatocytes

    PubMed Central

    Kim, Jung Wha; Yang, Heejung; Cho, Namki; Kim, Bitnarae; Kim, Young Choong; Sung, Sang Hyun

    2015-01-01

    Background: Ethanol causes hepatic cellular damage by alterations in biological functions. This study evaluated the hepatoprotective potential of the methanolic extract originating from Firmiana simplex (Sterculiaceae) stem bark against the ethanol-induced hepatotoxicity in rat primary hepatocytes. Materials and Methods: The extract of F. simplex stem bark was successively fractionated into n-hexane, chloroform, ethyl acetate (EtOAc), and n-butanol. Column chromatography with silica gel and sephadex LH-20 was used to isolate the EtOAc fraction. Rat primary hepatocytes were cultured to study the hepatoprotective activity of isolated substances against ethanol-induced toxicity. Intracellular reactive oxygen species (ROS) levels, the antioxidant activities of glutathione reductase (GR) and glutathione peroxidase (GSH-PX) enzymes, and the GSH content were measured to examine the antioxidative property of the isolated compounds. Results: Two flavonoid glycosides, quercitrin (1) and tamarixetin 3-O-rhamnopyranoside (2), were isolated from the active EtOAc fraction. Compound 1 significantly protected rat primary hepatocytes against ethanol-induced oxidative stress by reducing the intracellular ROS level and preserving antioxidative defense systems such as GR, GSH-PX, and total GSH. Conclusion: This is the first report on the hepatoprotective activities of the extract of F. simplex. The EtOAc fraction of F. simplex stem bark and its major constituent quercitrin (1) could function as hepatoprotective agents to attenuate the development of alcoholic liver disease. PMID:25709211

  14. Physically Based Modeling and Simulation with Dynamic Spherical Volumetric Simplex Splines

    PubMed Central

    Tan, Yunhao; Hua, Jing; Qin, Hong

    2009-01-01

    In this paper, we present a novel computational modeling and simulation framework based on dynamic spherical volumetric simplex splines. The framework can handle the modeling and simulation of genus-zero objects with real physical properties. In this framework, we first develop an accurate and efficient algorithm to reconstruct the high-fidelity digital model of a real-world object with spherical volumetric simplex splines which can represent with accuracy geometric, material, and other properties of the object simultaneously. With the tight coupling of Lagrangian mechanics, the dynamic volumetric simplex splines representing the object can accurately simulate its physical behavior because it can unify the geometric and material properties in the simulation. The visualization can be directly computed from the object’s geometric or physical representation based on the dynamic spherical volumetric simplex splines during simulation without interpolation or resampling. We have applied the framework for biomechanic simulation of brain deformations, such as brain shifting during the surgery and brain injury under blunt impact. We have compared our simulation results with the ground truth obtained through intra-operative magnetic resonance imaging and the real biomechanic experiments. The evaluations demonstrate the excellent performance of our new technique. PMID:20161636

  15. Herpes Simplex Virus Infection in a University Health Population: Clinical Manifestations, Epidemiology, and Implications

    ERIC Educational Resources Information Center

    Horowitz, Robert; Aierstuck, Sara; Williams, Elizabeth A.; Melby, Bernette

    2010-01-01

    Objective: The authors described clinical presentations of oral and genital herpes simplex virus (HSV) infections in a university health population and implications of these findings. Participants and Methods: Using a standardized data collection tool, 215 records of patients with symptomatic culture-positive HSV infections were reviewed. Results:…

  16. [Postoperative therapy after penetrating keratoplasty in herpes simplex keratitis].

    PubMed

    Süveges, Ildikó; Füst, Ágnes; Imre, László

    2013-12-29

    Bevezetés: A herpes simplex vírus által okozott szaruhártya-gyulladás a leggyakoribb oka a cornea centrumában kialakuló hegnek, amely látásvesztést okozhat. Célkitűzés: A szerzők célul tűzték ki a perforáló keratoplasztika eredményességének felmérését a szisztémás antiherpeses és immunszuppresszív terápia alkalmazásának tükrében. Módszer: Perforáló keratoplasztikán átesett 12 betegen végezték a retrospektív randomizált vizsgálatot. A műtéti beavatkozásig eltelt idő az első keratitis megjelenésétől számítva átlag 18 év volt (5–40 év). A műtéti indikáció 9 esetben a látás javítása, 3 esetben a cornea perforációjának megelőzése volt. Szisztémás kezelésként 9 beteg herpeszvírus elleni (acyclovir) és immunszuppresszív (mycophenolat mofetil), 2 beteg csak herpeszvírus elleni kezelést kapott, egy betegnél nem alkalmaztak szisztémás terápiát. Az átlagos követési idő 53,1 hónap volt (16–84 hó). Eredmények: A látásjavító célú 9 műtét közül 8 esetben a transzplantátum átlátszóan, ereződés nélkül gyógyult. Mind a 8 beteg acyclovir és mycophenolat mofetil kezelésben részesült. Egy esetben – amikor a beteg szisztémás kezelést nem kapott – recidíva és rejectio is fellépett. Az akut gyulladásos tünetekben végzett műtétek közül egyben gyógyult a transzplantátum átlátszóan, recidíva- és rejectiomentesen; a beteg acyclovir és mycophenolat mofetil terápiában részesült. Két esetben recidíva és rejectio is fellépett. Ezek közül egyben a beteg acyclovir és mycophenolat mofetil, egyben csak acyclovirkezelést kapott. A látóélesség minden esetben javult, 3 esetben a látást egyéb tényezők befolyásolták. Következtetések: A szisztémás acyclovir és mycophenolat mofetil terápia sikerrel alkalmazható herpes simplex keratitisben végzett perforáló keratoplasztikák után. Az acyclovir csökkenti a recidívák számát, a

  17. Structure of the C-Terminal Domain of the Multifunctional ICP27 Protein from Herpes Simplex Virus 1

    PubMed Central

    Dahlroth, Sue-Li; Rajakannan, Venkatachalam; Ho, Hai Ting; Cornvik, Tobias

    2015-01-01

    ABSTRACT Herpesviruses are nuclear-replicating viruses that have successfully evolved to evade the immune system of humans, establishing lifelong infections. ICP27 from herpes simplex virus is a multifunctional regulatory protein that is functionally conserved in all known human herpesviruses. It has the potential to interact with an array of cellular proteins, as well as intronless viral RNAs. ICP27 plays an essential role in viral transcription, nuclear export of intronless RNAs, translation of viral transcripts, and virion host shutoff function. It has also been implicated in several signaling pathways and the prevention of apoptosis. Although much is known about its central role in viral replication and infection, very little is known about the structure and mechanistic properties of ICP27 and its homologs. We present the first crystal structure of ICP27 C-terminal domain at a resolution of 2.0 Å. The structure reveals the C-terminal half of ICP27 to have a novel fold consisting of α-helices and long loops, along with a unique CHCC-type of zinc-binding motif. The two termini of this domain extend from the central core and hint to possibilities of making interactions. ICP27 essential domain is capable of forming self-dimers as seen in the structure, which is confirmed by analytical ultracentrifugation study. Preliminary in vitro phosphorylation assays reveal that this domain may be regulated by cellular kinases. IMPORTANCE ICP27 is a key regulatory protein of the herpes simplex virus and has functional homologs in all known human herpesviruses. Understanding the structure of this protein is a step ahead in deciphering the mechanism by which the virus thrives. In this study, we present the first structure of the C-terminal domain of ICP27 and describe its novel features. We critically analyze the structure and compare our results to the information available form earlier studies. This structure can act as a guide in future experimental designs and can add to a

  18. Inhibition of host protein synthesis and degradation of cellular mRNAs during infection by influenza and herpes simplex virus

    SciTech Connect

    Inglis, S.C.

    1982-12-01

    Cloned DNA copies of two cellular genes were used to monitor, by blot hybridization, the stability of particular cell mRNAs after infection by influenza virus and herpes virus. The results indicated that the inhibition of host cell protein synthesis that accompanied infection by each virus could be explained by a reduction in the amounts of cellular mRN As in the cytoplasm, and they suggested that this decrease was due to virus-mediated mRNA degradation.

  19. Double encephalitis with herpes simplex virus type II and cytomegalovirus in an elder Chinese: a case report

    PubMed Central

    Xue, Chaobiao; Chen, Shaoxian; Lin, Qi; Zhou, Houshi; Huang, Chuming; Lin, Jiyuan; Xie, Weihang; Chen, Kai; Zhou, Dongming; Ma, Wan; Ma, Feiyu; Xu, Haiyun

    2015-01-01

    Herpes simplex encephalitis is a rare disease. In adults, most of the reported cytomegalovirus (CMV) infections are seen in immunocompromised patients. We present a case of 67-year-old Chinese male with the coinfection of CMV and herpes simplex virus type II (HSV-II). He had no history of being treated with immunosuppressants, showed symptoms of psychosis and was scored 109 on the Positive and Negative Syndrome Scale. This patient presented with a rare case of coinfection of CMV and herpes simplex virus type II with psychotic symptoms. PMID:26586947

  20. Parasite diversity of Nyctiphanes simplex and Nematoscelis difficilis (Crustacea: Euphausiacea) along the northwestern coast of Mexico.

    PubMed

    Gómez-Gutiérrez, Jaime; Robinson, Carlos J; Kawaguchi, So; Nicol, Stephen

    2010-02-17

    The diversity of parasites found on Nyctiphanes simplex and Nematoscelis difficilis (Order Euphausiacea) was compared during 10 oceanographic cruises made off both coasts of the Baja California peninsula, Mexico. We tested the hypothesis that N. simplex has a more diverse parasitic assemblage than N. difficilis because it is a neritic species, has larger population abundance, and tends to form denser and more compact swarms than N. difficilis. These biological and behavioral features may enhance parasite transmission within swarms. We detected 6 types of ectoparasites: (1) epibiotic diatoms Licmophora sp.; (2) Ephelotidae suctorian ciliates; (3) Foettingeriidae exuviotrophic apostome ciliates; (4) an unidentified epicaridean cryptoniscus larvae (isopoda); and 2 castrators: (5) the ectoparasitic Dajidae isopod Notophryxus lateralis and (6) the ellobiopsid mesoparasite Thalassomyces fagei. We also detected 7 types of endoparasites: (1) an undescribed Collinia ciliate (Apostomatida); 3 types of Cestoda: (2) a Tetrarhynchobothruium sp. (Trypanorhyncha), (3) Echinobothrium sp. (Diphyllidea: Echinobothyriidae), and (4) unidentified metacestode; (5) a Trematoda Paronatrema-like metacercaria (Syncoeliidae); (6) the nematode Anisakis simplex (L3); and (7) Polymorphidae acantocephalan larvae (acanthor, acanthella, and cystacanth larval stages). N. simplex is affected by all types of parasites, except the isopod N. lateralis, having a considerably larger parasitic diversity and prevalence rates than N. difficilis, which is only infested with 3 types of ectoparasites and T. fagei. Euphausiid swarming is an adaptive behavior for reproduction, protection against predators, and increased efficiency in food searching, but has a negative effect due to parasitism. Although the advantages of aggregation must overcome the reduction of population and individual fitness induced by parasites, we demonstrated that all types of parasites can affect approximately 14% of N. simplex

  1. Mycosis Inhibits Cannibalism by Melanoplus sanguinipes, M. differentialis, Schistocerca americana, and Anabrus simplex

    PubMed Central

    Jaronski, Stefan T.

    2013-01-01

    Cannibalism is common among the Acrididae and the Mormon cricket, Anabrus simplex Haldeman (Orthoptera: Tettigoniidae). This behavior has been proposed as a mechanism for the horizontal transmission of Microsporida and entomopathogenic fungi. Aanecdotal observations suggested that the migratory grasshopper, Melanoplus sanguinipes Fabricius (Acrididae), and A. simplex did not eat cadavers that had been killed by insect pathogenic fungi. The hypothesis tested was that A. simplex or M. sanguinipes would not cannibalize individuals freshly killed by the entomopathogenic fungi, Beauveria bassiana Bals.-Criv. (Vuill.) (Hypocreales: Clavicipitaceae), or Metarhizium acridum (Driver and Milner) Bischoff, Rehner, and Humber. Cannibalism was examined in a series of no-choice tests with individual insects. Test insects included healthy adults of M. sanguinipes; the differential grasshopper, M. differentialis (Thomas); the American grasshopper, Schistocerca americana (Drury) (Acrididae); and A. simplex. Individual, starved Acrididae or A. simplex were confined in small cages with either a fungus-killed (but unsporulated) or uninfected cadaver. The insects were then observed periodically for the first 4 hr. After 24 hr, the cadavers were scored for the degree to which they had been consumed. Very few mycotic cadavers were fed upon by the healthy insects, and, at most only the tarsi were eaten. All four species generally refused to eat fungus-infected cadavers. In contrast, freeze-killed cadavers were partly or entirely consumed by most of the test insects, often within a few hours. Transmission of infection through contact in these tests was between 0–18.9%, depending upon the fungus and insect species, and was lower than the prevalence of cannibalism in all cases. PMID:24786183

  2. Virus-mediated chemical changes in rice plants impact the relationship between non-vector planthopper Nilaparvata lugens Stål and its egg parasitoid Anagrus nilaparvatae Pang et Wang.

    PubMed

    He, Xiaochan; Xu, Hongxing; Gao, Guanchun; Zhou, Xiaojun; Zheng, Xusong; Sun, Yujian; Yang, Yajun; Tian, Junce; Lu, Zhongxian

    2014-01-01

    In order to clarify the impacts of southern rice black-streaked dwarf virus (SRBSDV) infection on rice plants, rice planthoppers and natural enemies, differences in nutrients and volatile secondary metabolites between infected and healthy rice plants were examined. Furthermore, the impacts of virus-mediated changes in plants on the population growth of non-vector brown planthopper (BPH), Nilaparvata lugens, and the selectivity and parasitic capability of planthopper egg parasitoid Anagrus nilaparvatae were studied. The results showed that rice plants had no significant changes in amino acid and soluble sugar contents after SRBSDV infection, and SRBSDV-infected plants had no significant effect on population growth of non-vector BPH. A. nilaparvatae preferred BPH eggs both in infected and healthy rice plants, and tended to parasitize eggs on infected plants, but it had no significant preference for infected plants or healthy plants. GC-MS analysis showed that tridecylic aldehyde occurred only in rice plants infected with SRBSDV, whereas octanal, undecane, methyl salicylate and hexadecane occurred only in healthy rice plants. However, in tests of behavioral responses to these five volatile substances using a Y-tube olfactometer, A. nilaparvatae did not show obvious selectivity between single volatile substances at different concentrations and liquid paraffin in the control group. The parasitic capability of A. nilaparvatae did not differ between SRBSDV-infected plants and healthy plant seedlings. The results suggested that SRBSDV-infected plants have no significant impacts on the non-vector planthopper and its egg parasitoid, A. nilaparvatae. PMID:25141278

  3. Virus-Mediated Chemical Changes in Rice Plants Impact the Relationship between Non-Vector Planthopper Nilaparvata lugens Stål and Its Egg Parasitoid Anagrus nilaparvatae Pang et Wang

    PubMed Central

    Gao, Guanchun; Zhou, Xiaojun; Zheng, Xusong; Sun, Yujian; Yang, Yajun; Tian, Junce; Lu, Zhongxian

    2014-01-01

    In order to clarify the impacts of southern rice black-streaked dwarf virus (SRBSDV) infection on rice plants, rice planthoppers and natural enemies, differences in nutrients and volatile secondary metabolites between infected and healthy rice plants were examined. Furthermore, the impacts of virus-mediated changes in plants on the population growth of non-vector brown planthopper (BPH), Nilaparvata lugens, and the selectivity and parasitic capability of planthopper egg parasitoid Anagrus nilaparvatae were studied. The results showed that rice plants had no significant changes in amino acid and soluble sugar contents after SRBSDV infection, and SRBSDV-infected plants had no significant effect on population growth of non-vector BPH. A. nilaparvatae preferred BPH eggs both in infected and healthy rice plants, and tended to parasitize eggs on infected plants, but it had no significant preference for infected plants or healthy plants. GC-MS analysis showed that tridecylic aldehyde occurred only in rice plants infected with SRBSDV, whereas octanal, undecane, methyl salicylate and hexadecane occurred only in healthy rice plants. However, in tests of behavioral responses to these five volatile substances using a Y-tube olfactometer, A. nilaparvatae did not show obvious selectivity between single volatile substances at different concentrations and liquid paraffin in the control group. The parasitic capability of A. nilaparvatae did not differ between SRBSDV-infected plants and healthy plant seedlings. The results suggested that SRBSDV-infected plants have no significant impacts on the non-vector planthopper and its egg parasitoid, A. nilaparvatae. PMID:25141278

  4. Brazilein from Caesalpinia sappan L. Antioxidant Inhibits Adipocyte Differentiation and Induces Apoptosis through Caspase-3 Activity and Anthelmintic Activities against Hymenolepis nana and Anisakis simplex

    PubMed Central

    Liang, Chia-Hua; Chan, Leong-Perng; Chou, Tzung-Han; Chiang, Feng-Yu; Yen, Chuan-Min; Chen, Pin-Ju; Ding, Hsiou-Yu

    2013-01-01

    Brazilein, a natural, biologically active compound from Caesalpinia sappan L., has been shown to exhibit anti-inflammatory and antioxidant properties and to inhibit the growth of several cancer cells. This study verifies the antioxidant and antitumor characteristics of brazilein in skin cancer cells and is the first time to elucidate the inhibition mechanism of adipocyte differentiation, cestocidal activities against Hymenolepis nana, and reduction of spontaneous movement in Anisakis simplex. Brazilein exhibits an antioxidant capacity as well as the ability to scavenge DPPH• and ABTS•+ free radicals and to inhibit lipid peroxidation. Brazilein inhibited intracellular lipid accumulation during adipocyte differentiation in 3T3-L1 cells and suppressed the induction of peroxisome proliferator-activated receptor γ (PPARγ), the master regulator of adipogenesis, suggesting that brazilein presents the antiobesity effects. The toxic effects of brazilein were evaluated in terms of cell viability, induction of apoptosis, and the activity of caspase-3 in BCC cells. The inhibition of the growth of skin cancer cells (A431, BCC, and SCC25) by brazilein is greater than that of human skin malignant melanoma (A375) cells, mouse leukemic monocyte macrophage (RAW 264.7 cells), and noncancerous cells (HaCaT and BNLCL2 cells). The anthelmintic activities of brazilein against Hymenolepis nana are better than those of Anisakis simplex. PMID:23554834

  5. Adeno-Associated Virus Mediated Delivery of An Engineered Protein that Combines the Complement Inhibitory Properties of CD46, CD55 and CD59

    PubMed Central

    Leaderer, Derek; Cashman, Siobhan M.; Kumar-Singh, Rajendra

    2015-01-01

    Background A variety of disorders are associated with the activation of complement. CD46, CD55 and CD59 are the major membrane associated regulators of complement on human cells. Previously, we have found that independent expression of CD55, CD46 or CD59 through gene transfer protects murine tissues against human complement mediated attack. Herein we investigated the potential of combining the complement regulatory properties of CD46, CD55 and CD59 into single gene products expressed from an adeno-associated virus (AAV) vector in a soluble non-membrane anchored form. Methods Minigenes encoding the complement regulatory domains from CD46, CD55 and CD59 (SACT) or CD55 and CD59 (DTAC) were cloned into an AAV vector. The specific regulatory activity of each component of SACT and DTAC was measured in vitro. The recombinant AAV vectors were injected into the peritoneum of mice and the efficacy of the transgene products for being able to protect murine liver vasculature against human complement, specifically the membrane attack complex (MAC) was measured. Results SACT and DTAC exhibited properties similar to CD46, CD55 and CD59 or CD55 and CD59 respectively in vitro. AAV mediated delivery of SACT or DTAC protected murine liver vasculature from human MAC deposition by 63.2% and 56.7% respectively. Conclusions When delivered to mice in vivo via an AAV vector, SACT and DTAC are capable of limiting human complement mediated damage. SACT and DTAC merit further study as potential therapies for complement mediated disorders when delivered via a gene therapy approach. PMID:25917932

  6. PREVALENCE OF HERPES SIMPLEX VIRUS TYPE 2 AND RISK FACTORS ASSOCIATED WITH THIS INFECTION IN WOMEN IN SOUTHERN BRAZIL

    PubMed Central

    Caldeira, Thaís Duquia Moraes; Gonçalves, Carla Vitola; de Oliveira, Gisele Rodrigues; da Fonseca, Tânia Vieira; Gonçalves, Regina; do Amaral, Clair Teixeira; da Hora, Vanusa Pousada; de Martinez, Ana Maria Barral

    2013-01-01

    SUMMARY The herpes simplex virus type 2 (HVS-2) is the most prevalent infection worldwide. It is a cofactor in the acquisition of human immunodeficiency virus (HIV) and the persistence of human papillomavirus (HPV). This study evaluated the prevalence of HSV-2, using the polymerase chain reaction (PCR), and associated factors in patients treated at the Federal University of Rio Grande (FURG) and Basic Health Units (BHU) in Rio Grande, Brazil. The observed prevalence of HSV-2 was 15.6%. Among the 302 women studied, 158 had received assistance in BHU and 144 were treated at FURG. The prevalence of HSV-2 in these groups was 10.8% and 20.8%, respectively, RR 1.9 and p = 0.012. Knowledge about the Pap smear, and the presence of lesions showed no association with HSV-2 infection. Multivariate analysis showed that the variable that most influenced the risk of HSV-2 infection was the presence of HIV infection, with a relative risk of 1.9 and p = 0.04. Discussion: Genital ulcers are an important entry point for HIV, and condom use is an important strategy to reduce transmission of HIV and HSV-2. PMID:24037285

  7. Inhibition of herpes simplex virus 1 gene expression and replication by RNase P-associated external guide sequences

    PubMed Central

    Liu, Jin; Shao, Luyao; Trang, Phong; Yang, Zhu; Reeves, Michael; Sun, Xu; Vu, Gia-Phong; Wang, Yu; Li, Hongjian; Zheng, Congyi; Lu, Sangwei; Liu, Fenyong

    2016-01-01

    An external guide sequence (EGS) is a RNA sequence which can interact with a target mRNA to form a tertiary structure like a pre-tRNA and recruit intracellular ribonuclease P (RNase P), a tRNA processing enzyme, to degrade target mRNA. Previously, an in vitro selection procedure has been used by us to engineer new EGSs that are more robust in inducing human RNase P to cleave their targeted mRNAs. In this study, we constructed EGSs from a variant to target the mRNA encoding herpes simplex virus 1 (HSV-1) major transcription regulator ICP4, which is essential for the expression of viral early and late genes and viral growth. The EGS variant induced human RNase P cleavage of ICP4 mRNA sequence 60 times better than the EGS generated from a natural pre-tRNA. A decrease of about 97% and 75% in the level of ICP4 gene expression and an inhibition of about 7,000- and 500-fold in viral growth were observed in HSV infected cells expressing the variant and the pre-tRNA-derived EGS, respectively. This study shows that engineered EGSs can inhibit HSV-1 gene expression and viral growth. Furthermore, these results demonstrate the potential for engineered EGS RNAs to be developed and used as anti-HSV therapeutics. PMID:27279482

  8. Safety, formulation, and in vitro antiviral activity of the antimicrobial peptide subtilosin against herpes simplex virus type 1

    PubMed Central

    Torres, Nicolás I.; Noll, Katia Sutyak; Xu, Shiqi; Li, Ji; Huang, Qingrong; Sinko, Patrick J.; Wachsman, Mónica B.; Chikindas, Michael L.

    2013-01-01

    In the present study the antiviral properties of the bacteriocin subtilosin against Herpes simplex virus type 1 (HSV-1) and the safety and efficacy of a subtilosin-based nanofiber formulation were determined. High concentrations of subtilosin, the cyclical antimicrobial peptide produced by Bacillus amyloliquefaciens, were virucidal against HSV-1. Interestingly, at non-virucidal concentrations, subtilosin inhibited wild type HSV-1 and aciclovir-resistant mutants in a dose-dependent manner. Although the exact antiviral mechanism is not fully understood, time of addition experiments and western blot analysis suggest that subtilosin does not affect viral multiplication steps prior to protein synthesis. Poly(vinyl alcohol) (PVOH)-based subtilosin nanofibers with a width of 278 nm were produced by the electrospinning process. The retained antimicrobial activity of the subtilosin-based fibers was determined via an agar well diffusion assay. The loading capacity of the fibers was 2.4 mg subtilosin/g fiber, and loading efficiency was 31.6%. Furthermore, the nanofibers with and without incorporated subtilosin were shown to be nontoxic to human epidermal tissues using an in vitro human tissue model. Taking together these results subtilosin-based nanofibers should be further studied as a novel alternative method for treatment and/or control of HSV-1 infection. PMID:23637711

  9. Extended Release of an Anti–Heparan Sulfate Peptide From a Contact Lens Suppresses Corneal Herpes Simplex Virus-1 Infection

    PubMed Central

    Jaishankar, Dinesh; Buhrman, Jason S.; Valyi-Nagy, Tibor; Gemeinhart, Richard A.; Shukla, Deepak

    2016-01-01

    Purpose To prolong the release of a heparan sulfate binding peptide, G2-C, using a commercially available contact lens as a delivery vehicle and to demonstrate the ability of the released peptide to block herpes simplex virus-1 (HSV-1) infection using in vitro, ex vivo, and in vivo models of corneal HSV-1 infection. Methods Commercially available contact lenses were immersed in peptide solution for 5 days prior to determining the release of the peptide at various time points. Cytotoxicity of the released samples was determined by MTT and cell cycle analysis, and the functional activity of the released samples were assessed by viral entry, and viral spread assay using human corneal epithelial cells (HCE). The ability to suppress infection in human and pig cornea ex vivo and mouse in vivo models were also assessed. Results Peptide G2-C was released through the contact lens. Following release for 3 days, the peptide showed significant activity by inhibiting HSV-1 viral entry and spread in HCE cells. Significant suppression of infection was also observed in the ex vivo and in vivo experiments involving corneas. Conclusions Extended release of an anti–HS peptide through a commercially available contact lens can generate significant anti–HSV-1 activity and provides a new and effective way to control corneal herpes. PMID:26780322

  10. Atypical presentations of genital herpes simplex virus in HIV-1 and HIV-2 effectively treated by imiquimod.

    PubMed

    McKendry, Anna; Narayana, Srinivasulu; Browne, Rita

    2015-05-01

    Atypical presentations of genital herpes simplex virus have been described in HIV. We report two cases with hypertrophic presentations which were effectively treated with imiquimod, one of which is the first reported case occurring in a patient with HIV-2.

  11. Molecular epidemiology and risk factors for Anisakis simplex s.l. infection in blue whiting (Micromesistius poutassou) in a confluence zone of the Atlantic and Mediterranean: Differences between A. simplex s.s. and A. pegreffii.

    PubMed

    Gómez-Mateos, Magdalena; Valero, Adela; Morales-Yuste, Manuel; Martín-Sánchez, Joaquina

    2016-09-01

    Our study determined parameters of parasitization of Anisakis simplex s.l. in Micromesistius poutassou in a confluence zone of the Atlantic and Mediterranean, with a total prevalence of 82%. Also, in the three seasons analyzed, high prevalence's values were found, reaching 100% in spring; however mean intensity and abundance values were higher in winter. The use of molecular techniques to differentiate between Anisakis genotypes of the larvae characterized allowed obtaining values of 99.7% Anisakis simplex s.l. (50.1% A. simplex s.s., 42.9% A. pegreffii, 7.0% A. simplex s.s. - A. pegreffii hybrids) and 0.3% A. typica. The infections found in the fish were of both single and mixed species, in all the different possible combinations. The presence of A. simplex s.l. in the viscera varied according to genotype and season. Likewise, factors associated with the presence of the parasite in the ventral or dorsal musculature were different, where A. simplex s.s. proportion was double than that of A. pegreffii. The ecology of the two sibling species with regard to their location in fish and the influence of the season were different.

  12. Expression of Herpes Simplex Virus 1 Glycoprotein B by a Recombinant Vaccinia Virus and Protection of Mice against Lethal Herpes Simplex Virus 1 Infection

    NASA Astrophysics Data System (ADS)

    Cantin, Edouard M.; Eberle, Richard; Baldick, Joseph L.; Moss, Bernard; Willey, Dru E.; Notkins, Abner L.; Openshaw, Harry

    1987-08-01

    The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modified at the 5' end by in vitro oligonucleotide-directed mutagenesis. The modified gB gene was inserted into the vaccinia virus genome and expressed under the control of a vaccinia virus promoter. The mature gB glycoprotein produced by the vaccinia virus recombinant was glycosylated, was expressed at the cell surface, and was indistinguishable from authentic HSV-1 gB in terms of electrophoretic mobility. Mice immunized intradermally with the recombinant vaccinia virus produced gB-specific neutralizing antibodies and were resistant to a lethal HSV-1 challenge.

  13. Host Anti-antibody Responses Following Adeno-associated Virus-mediated Delivery of Antibodies Against HIV and SIV in Rhesus Monkeys.

    PubMed

    Martinez-Navio, José M; Fuchs, Sebastian P; Pedreño-López, Sònia; Rakasz, Eva G; Gao, Guangping; Desrosiers, Ronald C

    2016-02-01

    Long-term delivery of antibodies against the human immunodeficiency virus (HIV) using adeno-associated virus (AAV) vectors is a promising approach for the prevention or treatment of HIV infection. However, host antibody responses to the delivered antibody are a serious concern that could significantly limit the applicability of this approach. Here, we describe the dynamics and characteristics of the anti-antibody responses in monkeys that received either rhesus anti-simian immunodeficiency virus (SIV) antibodies (4L6 or 5L7) in prevention trials or a combination of rhesusized human anti-HIV antibodies (1NC9/8ANC195/3BNC117 or 10-1074/10E8/3BNC117) in therapy trials, all employing AAV1 delivery of IgG1. Eight out of eight monkeys that received the anti-HIV antibodies made persisting antibody responses to all three antibodies in the mix. Six out of six uninfected monkeys that received the anti-SIV antibody 4L6 and three out of six of those receiving anti-SIV antibody 5L7 also generated anti-antibodies. Both heavy and light chains were targeted, predominantly or exclusively to variable regions, and reactivity to complementarity-determining region (CDR)-H3 peptide could be demonstrated. There was a highly significant correlation of the magnitude of anti-antibody responses with the degree of sequence divergence of the delivered antibody from germline. Our results suggest the need for effective strategies to counteract the problem of antibody responses to AAV-delivered antibodies.

  14. The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses

    PubMed Central

    2014-01-01

    Background There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD. Methods In a unique public-private partnership, 13 sites with extensive experience in both the assessment and diagnosis of ASD embarked on an ambitious, 2-year program to collect samples for genetic and phenotypic research and begin analyses on these samples. The program was called The Autism Simplex Collection (TASC). TASC sample collection began in 2008 and was completed in 2010, and included nine sites from North America and four sites from Western Europe, as well as a centralized Data Coordinating Center. Results Over 1,700 trios are part of this collection, with DNA from transformed cells now available through the National Institute of Mental Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic (ADOS-G) measures are available for all probands, as are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and physical measures (height, weight, and head circumference). At almost every site, additional phenotypic measures were collected, including the Broad Autism Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as well as the non-word repetition scale, Communication Checklist (Children’s or Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios, the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP genotyping and called copy number variation (CNV) in the samples, with data being made available through the National Institutes of Health (NIH). Whole exome sequencing (WES) has been carried out in over 500 probands, together with ancestry matched controls, and this data is also available through the NIH. Additional WES is being carried out by the Autism Sequencing Consortium (ASC), where the

  15. Macrophages and cytokines in the early defence against herpes simplex virus

    PubMed Central

    Ellermann-Eriksen, Svend

    2005-01-01

    Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone

  16. Cross-linking of glycoprotein oligomers during herpes simplex virus type 1 entry.

    PubMed

    Handler, C G; Cohen, G H; Eisenberg, R J

    1996-09-01

    Herpes simplex virus (HSV) has 10 glycoproteins in its envelope. Glycoprotein B (gB), gC, gD, gH, and gL have been implicated in virus entry. We previously used chemical cross-linking to show that these five glycoproteins were close enough to each other to be cross-linked into homodimeric and hetero-oligomeric forms; hetero-oligomers of gB-gC, gC-gD, gD-gB, gH-gL, gC-gL and gD-gL were found in purified virions. To better understand the roles of these glycoproteins in viral entry, we have modified a standard HSV penetration assay to include cross-linkers. This allowed us to examine changes in associations of viral glycoproteins during the entry process. HSV-1(KOS) was adsorbed at 4 degrees C to human neuroblastoma cells (SY5Y). The temperature was raised to 37 degrees C and cells were treated with cross-linker at various times after the temperature shift. Cytoplasmic extracts were examined by Western blotting (immunoblotting) for viral glycoproteins. We found that (i) as in virus alone, the length and concentration of the cross-linking agent affected the number of specific complexes isolated; (ii) the same glycoprotein patterns found in purified virions were also present after attachment of virions to cells; and (iii) the ability to cross-link HSV glycoproteins changed as virus penetration proceeded, e.g., gB and gD complexes which were present during attachment disappeared with increasing time, and their disappearance paralleled the kinetics of penetration. However, this phenomenon appeared to be selective since it was not observed with gC oligomers. In addition, we examined the cross-linking patterns of gB and gD in null viruses K082 and KOSgD beta. Neither of these mutants, which attach but cannot penetrate, showed changes in glycoprotein cross-linking over time. We speculate that these changes are due to conformational changes which preclude cross-linking or spatial alterations which dissociate the glycoprotein interactions during the penetration events. PMID

  17. The treatment of herpes simplex virus epithelial keratitis.

    PubMed Central

    Wilhelmus, K R

    2000-01-01

    PURPOSE: Epithelial keratitis is the most common presentation of ocular infection by herpes simplex virus (HSV). Quantitative assessment of available therapy is needed to guide evidence-based ophthalmology. This study aimed to compare the efficacy of various treatments for dendritic or geographic HSV epithelial keratitis and to evaluate the role of various clinical characteristics on epithelial healing. METHODS: Following a systematic review of the literature, information from clinical trials of HSV dendritic or geographic epithelial keratitis was extracted, and the methodological quality of each study was scored. Methods of epithelial cauterization and curettage were grouped as relatively equivalent physicochemical therapy, and solution and ointment formulations of a given topical antiviral agent were combined. The proportion healed with 1 week of therapy, a scheduled follow-up day that approximated the average time of resolution with antiviral therapy, was selected as the primary outcome based on a masked evaluation of maximum treatment differences in published healing curves. The proportion healed at 14 days was recorded as supplemental information. Fixed-effects and random-effects meta-analysis models were used to obtain summary estimates by pooling results from comparative treatment trials. Hypotheses about which prognostic factors might affect epithelial healing during antiviral therapy were developed by multivariate analysis of the Herpetic Eye Disease Study dataset. RESULTS: After excluding 48 duplicate reports, 14 nonrandomized studies, 15 studies with outdated or similar treatments, and 29 trials lacking sufficient data on healing or accessibility, 76 primary reports were identified. These reports involved 4,251 patients allocated to 93 treatment comparisons of dendritic epithelial keratitis in 28 categories and 9 comparisons of geographic epithelial keratitis in 6 categories. For dendritic keratitis, idoxuridine was better than placebo at 7 days

  18. The treatment of herpes simplex virus epithelial keratitis.

    PubMed Central

    Wilhelmus, K R

    2000-01-01

    PURPOSE: Epithelial keratitis is the most common presentation of ocular infection by herpes simplex virus (HSV). Quantitative assessment of available therapy is needed to guide evidence-based ophthalmology. This study aimed to compare the efficacy of various treatments for dendritic or geographic HSV epithelial keratitis and to evaluate the role of various clinical characteristics on epithelial healing. METHODS: Following a systematic review of the literature, information from clinical trials of HSV dendritic or geographic epithelial keratitis was extracted, and the methodological quality of each study was scored. Methods of epithelial cauterization and curettage were grouped as relatively equivalent physicochemical therapy, and solution and ointment formulations of a given topical antiviral agent were combined. The proportion healed with 1 week of therapy, a scheduled follow-up day that approximated the average time of resolution with antiviral therapy, was selected as the primary outcome based on a masked evaluation of maximum treatment differences in published healing curves. The proportion healed at 14 days was recorded as supplemental information. Fixed-effects and random-effects meta-analysis models were used to obtain summary estimates by pooling results from comparative treatment trials. Hypotheses about which prognostic factors might affect epithelial healing during antiviral therapy were developed by multivariate analysis of the Herpetic Eye Disease Study dataset. RESULTS: After excluding 48 duplicate reports, 14 nonrandomized studies, 15 studies with outdated or similar treatments, and 29 trials lacking sufficient data on healing or accessibility, 76 primary reports were identified. These reports involved 4,251 patients allocated to 93 treatment comparisons of dendritic epithelial keratitis in 28 categories and 9 comparisons of geographic epithelial keratitis in 6 categories. For dendritic keratitis, idoxuridine was better than placebo at 7 days

  19. Dynamic Response of IFI16 and Promyelocytic Leukemia Nuclear Body Components to Herpes Simplex Virus 1 Infection

    PubMed Central

    2015-01-01

    ABSTRACT Intrinsic immunity is an aspect of antiviral defense that operates through diverse mechanisms at the intracellular level through a wide range of constitutively expressed cellular proteins. In the case of herpesviruses, intrinsic resistance involves the repression of viral gene expression during the very early stages of infection, a process that is normally overcome by viral tegument and/or immediate-early proteins. Thus, the balance between cellular repressors and virus-counteracting proteins determines whether or not a cell becomes productively infected. One aspect of intrinsic resistance to herpes simplex virus 1 (HSV-1) is conferred by components of promyelocytic leukemia nuclear bodies (PML NBs), which respond to infection by accumulating at sites that are closely associated with the incoming parental HSV-1 genomes. Other cellular proteins, including IFI16, which has been implicated in sensing pathogen DNA and initiating signaling pathways that lead to an interferon response, also respond to viral genomes in this manner. Here, studies of the dynamics of the response of PML NB components and IFI16 to invading HSV-1 genomes demonstrated that this response is extremely rapid, occurring within the first hour after addition of the virus, and that human Daxx (hDaxx) and IFI16 respond more rapidly than PML. In the absence of HSV-1 regulatory protein ICP0, which counteracts the recruitment process, the newly formed, viral-genome-induced PML NB-like foci can fuse with existing PML NBs. These data are consistent with a model involving viral genome sequestration into such structures, thereby contributing to the low probability of initiation of lytic infection in the absence of ICP0. IMPORTANCE Herpesviruses have intimate interactions with their hosts, with infection leading either to the productive lytic cycle or to a quiescent infection in which viral gene expression is suppressed while the viral genome is maintained in the host cell nucleus. Whether a cell

  20. Herpes Simplex Virus 1 Reactivates from Autonomic Ciliary Ganglia Independently from Sensory Trigeminal Ganglia To Cause Recurrent Ocular Disease

    PubMed Central

    Lee, Sungseok; Ives, Angela M.

    2015-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) and HSV-2 establish latency in sensory and autonomic neurons after ocular or genital infection, but their recurrence patterns differ. HSV-1 reactivates from latency to cause recurrent orofacial disease, and while HSV-1 also causes genital lesions, HSV-2 recurs more efficiently in the genital region and rarely causes ocular disease. The mechanisms regulating these anatomical preferences are unclear. To determine whether differences in latent infection and reactivation in autonomic ganglia contribute to differences in HSV-1 and HSV-2 anatomical preferences for recurrent disease, we compared HSV-1 and HSV-2 clinical disease, acute and latent viral loads, and viral gene expression in sensory trigeminal and autonomic superior cervical and ciliary ganglia in a guinea pig ocular infection model. HSV-2 produced more severe acute disease, correlating with higher viral DNA loads in sensory and autonomic ganglia, as well as higher levels of thymidine kinase expression, a marker of productive infection, in autonomic ganglia. HSV-1 reactivated in ciliary ganglia, independently from trigeminal ganglia, to cause more frequent recurrent symptoms, while HSV-2 replicated simultaneously in autonomic and sensory ganglia to cause more persistent disease. While both HSV-1 and HSV-2 expressed the latency-associated transcript (LAT) in the trigeminal and superior cervical ganglia, only HSV-1 expressed LAT in ciliary ganglia, suggesting that HSV-2 is not reactivation competent or does not fully establish latency in ciliary ganglia. Thus, differences in replication and viral gene expression in autonomic ganglia may contribute to differences in HSV-1 and HSV-2 acute and recurrent clinical disease. IMPORTANCE Herpes simplex virus 1 (HSV-1) and HSV-2 establish latent infections, from which the viruses reactivate to cause recurrent disease throughout the life of the host. However, the viruses exhibit different manifestations and frequencies of recurrent

  1. Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus and Vesicular Stomatitis Virus Replication in Sensory Neurons and Fibroblasts

    PubMed Central

    Rosato, Pamela C.

    2014-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity to reactivate. The interferon (IFN)-driven antiviral response is critical for the control of HSV-1 acute replication. We therefore sought to further investigate this response in TG neurons cultured from adult mice deficient in a variety of IFN signaling components. Parallel experiments were also performed in fibroblasts isolated concurrently. We showed that HSV-1 replication was comparable in wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus (VSV). Despite these findings, TG neurons responded to IFN-β pretreatment with STAT1 nuclear localization and restricted replication of both VSV and an HSV-1 strain deficient in γ34.5, while wild-type HSV-1 replication was unaffected. This was in contrast to fibroblasts in which all viruses were restricted by the addition of IFN-β. Taken together, these data show that adult TG neurons can mount an effective antiviral response only if provided with an exogenous source of IFN-β, and HSV-1 combats this response through γ34.5. These results further our understanding of the antiviral response of neurons and highlight the importance of paracrine IFN-β signaling in establishing an antiviral state. IMPORTANCE Herpes simplex virus 1 (HSV-1) is a ubiquitous virus that establishes a lifelong latent infection in neurons. Reactivation from latency can cause cold sores, blindness, and death from encephalitis. Humans with deficiencies in innate immunity have significant problems controlling HSV infections. In this study, we therefore sought to elucidate the role of neuronal innate immunity in the control of viral infection. Using neurons isolated from mice, we found that the intrinsic capacity of neurons to restrict virus replication was unaffected by the presence

  2. Genetic simplex modeling of Eysenck's dimensions of personality in a sample of young Australian twins.

    PubMed

    Gillespie, Nathan A; Evans, David E; Wright, Margie M; Martin, Nicholas G

    2004-12-01

    The relative stability and magnitude of genetic and environmental effects underlying major dimensions of adolescent personality across time were investigated. The Junior Eysenck Personality Questionnaire was administered to over 540 twin pairs at ages 12, 14 and 16 years. Their personality scores were analyzed using genetic simplex modeling which explicitly took into account the longitudinal nature of the data. With the exception of the dimension lie, multivariate model fitting results revealed that familial aggregation was entirely explained by additive genetic effects. Results from simplex model fitting suggest that large proportions of the additive genetic variance observed at ages 14 and 16 years could be explained by genetic effects present at the age of 12 years. There was also evidence for smaller but significant genetic innovations at 14 and 16 years of age for male and female neuroticism, at 14 years for male extraversion, at 14 and 16 years for female psychoticism, and at 14 years for male psychoticism.

  3. Cross-reactivity between antigens of Anisakis simplex s.l. and other ascarid nematodes.

    PubMed

    Lozano, Maldonado J; Martín, Hita L; Díaz, Sáez V; Mañas, Almendros I; Valero, López A; Campos, Bueno M

    2004-06-01

    A study of the cross-reactivity among somatic and excretory-secretory antigens of the third stage larvae of Anisakis simplex s.l. and somatic antigens of other ascarid nematodes (Ascaris lumbricoides, A. suum, Toxocara canis, Anisakis physeteris, Hysterothylacium aduncum and H. fabri) was carried out by immunoblotting. It was revealed a high degree of cross-reactivity among ascarids in the 30 and > 212 kDa range by using sera against somatic and excretory-secretory antigens of A. simplex s.l. It has been revealed also specific components of the Anisakis genus (< 7.2, 9, 19 and 25 kDa) that will be interesting in diagnosis. PMID:15224584

  4. Analysis of the eclipsing binary ST Carinae using the SIMPLEX algorithm

    SciTech Connect

    Walker, R.L.; Chambliss, C.R. Kutztown Univ., PA )

    1990-07-01

    This work presents the analyses of two UBV data sets for the Algol binary ST Carinae, presenting a homogeneous study of all the data. The light-curve parameters for the system are derived using the Wilson-Devinney model (1917), with the SIMPLEX algorithm as an optimization procedure, and a mass ratio of q=0.54 is obtained. The primary has colors consistent with a B9.5 V primary, and the solution indicates that the secondary is an F subgiant (Te=6200 K) that fills its Roche lobe. The application of Kepler's law (using the observed period and the mass ratio determined in this investigation) indicates that the absolute dimensions for the components are normal for their respective classes. A description of SIMPLEX is given, and its advantages for the solution of eclipsing binary parameters are discussed. 19 refs.

  5. Transmission of herpes simplex virus type 1 infection in rugby players.

    PubMed

    White, W B; Grant-Kels, J M

    1984-07-27

    Skin infections, both bacterial and viral, are endemic in contact sports such as wrestling and rugby football. In this report, we describe four cases of extensive cutaneous herpes simplex virus in players on a rugby team. All players had a prodrome of fever, malaise, and anorexia with a weight loss of 3.6 to 9.0 kg. Two players experienced ocular lesions associated with cutaneous vesicular lesions of the face. A third player, who had herpetic lesions on his lower extremity, experienced paresthesias, weakness, and intermittent urinary retention and constipation. All infected players on the team were forwards or members of the "scrum," which suggests a field-acquired infection analogous to the herpetic infections seen in wrestlers (herpes gladiatorum). Considering the serious sequelae of recurrent herpes simplex keratitis, the traumatic skin lesions in rugby football players should be cultured for herpes virus, and infected individuals should be restricted from playing until crusted lesions have disappeared. PMID:6737650

  6. Connecting the dots : analysis, development and applications of the SimpleX algorithm

    NASA Astrophysics Data System (ADS)

    Kruip, Chael

    2011-11-01

    The SimpleX radiative transfer method is based on the interpretation of photons as particles interacting on a natural scale: the local mean free path. In our method, light is transported along the lines of an unstructured Delaunay mesh that encodes this natural distance and represents the physical medium. The SimpleX method is fast, highly adaptive and its computational cost does not scale with the number of sources. It is therefore well-suited for cosmological applications where it is essential to cover many orders of magnitude in resolution and where millions of sources can exist within a single simulation. We describe the code, its recent developments and apply it to several relevant astrophysical problems. In particular, we perform radiative transfer calculations of cosmological reionization and of the wind-wind interaction region of the Eta Carinae binary system.

  7. Application of low-intensity laser in the treatment of Herpes simplex recidivans

    NASA Astrophysics Data System (ADS)

    Uzunov, Tzonko T.; Uzunov, T.; Grozdanova, R.

    2004-06-01

    We made our aim to investigate the effect of the low intensive laser with λ=630 nm in the visible red spectrum of light at Herpes simplex treatment. For this purpose we carried out a clinical research upon 62 persons with Herpes simplex lesions which have been divided into two groups of 31 persons. At the first group the effect of laser with power density 100 mW/cm2 +/- 5 mW/cm2 and time of exposure 3 min. on field was traced out. At the second group the low intensive laser with the same characteristics has been used but in combination with the patent medicine Granofurin H as a photosensibilizer. The clinical approbations of this method showed high therapeutical effectiveness. The obtained results showed that at both groups there is an expressed anaesthetic, anti-inflammatory and regeneration stimulating effect and at the second group with the use of Granofurin H the reconvalescent period is shorter.

  8. Functional Characterization of Glycoprotein H Chimeras Composed of Conserved Domains of the Pseudorabies Virus and Herpes Simplex Virus 1 Homologs

    PubMed Central

    Böhm, Sebastian W.; Backovic, Marija; Klupp, Barbara G.; Rey, Felix A.; Fuchs, Walter

    2015-01-01

    herpesviruses can serve as tools to elucidate the molecular basis of gH function. The present study shows that the C-terminal part of human herpesvirus 1 (herpes simplex virus 1) gH can functionally substitute for the corresponding part of suid herpesvirus 1 (pseudorabies virus) gH, whereas other tested combinations proved to be nonfunctional. Interestingly, the exchangeable fragment included the membrane-proximal end of the gH ectodomain (domain IV), which is most conserved in sequence and structure and might be capable of transient membrane interaction during fusion. PMID:26491153

  9. Optimization of Recombinant Adeno-Associated Virus-Mediated Expression for Large Transgenes, Using a Synthetic Promoter and Tandem Array Enhancers

    PubMed Central

    Yan, Ziying; Sun, Xingshen; Feng, Zehua; Li, Guiying; Fisher, John T.; Stewart, Zoe A.

    2015-01-01

    Abstract The packaging capacity of recombinant adeno-associated viral (rAAV) vectors limits the size of the promoter that can be used to express the 4.43-kb cystic fibrosis transmembrane conductance regulator (CFTR) cDNA. To circumvent this limitation, we screened a set of 100-mer synthetic enhancer elements, composed of ten 10-bp repeats, for their ability to augment CFTR transgene expression from a short 83-bp synthetic promoter in the context of an rAAV vector designed for use in the cystic fibrosis (CF) ferret model. Our initial studies assessing transcriptional activity in monolayer (nonpolarized) cultures of human airway cell lines and primary ferret airway cells revealed that three of these synthetic enhancers (F1, F5, and F10) significantly promoted transcription of a luciferase transgene in the context of plasmid transfection. Further analysis in polarized cultures of human and ferret airway epithelia at an air–liquid interface (ALI), as well as in the ferret airway in vivo, demonstrated that the F5 enhancer produced the highest level of transgene expression in the context of an AAV vector. Furthermore, we demonstrated that increasing the size of the viral genome from 4.94 to 5.04 kb did not significantly affect particle yield of the vectors, but dramatically reduced the functionality of rAAV-CFTR vectors because of small terminal deletions that extended into the CFTR expression cassette of the 5.04-kb oversized genome. Because rAAV-CFTR vectors greater than 5 kb in size are dramatically impaired with respect to vector efficacy, we used a shortened ferret CFTR minigene with a 159-bp deletion in the R domain to construct an rAAV vector (AV2/2.F5tg83-fCFTRΔR). This vector yielded an ∼17-fold increase in expression of CFTR and significantly improved Cl– currents in CF ALI cultures. Our study has identified a small enhancer/promoter combination that may have broad usefulness for rAAV-mediated CF gene therapy to the airway. PMID:25763813

  10. Draft Genome Sequence of Bacillus simplex DSM 1321 for Setting Up Phylogenomics in Genomic Taxonomy of the Bacillus-Like Bacteria

    PubMed Central

    Liu, Guo-hong; Wang, Jie-ping; Che, Jian-mei; Chen, Qian-qian; Chen, Zheng

    2016-01-01

    Bacillus simplex DSM 1321 is a Gram-positive, spore-forming, and aerobic bacterium. Here, we report the draft genome sequence of B. simplex DSM 1321, with 6,494,937 bp, which will provide useful information for setting up phylogenomics in genomic taxonomy of the Bacillus-like bacteria as well as for the functional gene mining and application of B. simplex DSM 1321. PMID:27340061

  11. The Intelligence of Dual Simplex Method to Solve Linear Fractional Fuzzy Transportation Problem

    PubMed Central

    Narayanamoorthy, S.; Kalyani, S.

    2015-01-01

    An approach is presented to solve a fuzzy transportation problem with linear fractional fuzzy objective function. In this proposed approach the fractional fuzzy transportation problem is decomposed into two linear fuzzy transportation problems. The optimal solution of the two linear fuzzy transportations is solved by dual simplex method and the optimal solution of the fractional fuzzy transportation problem is obtained. The proposed method is explained in detail with an example. PMID:25810713

  12. Ascending in utero herpes simplex virus infection in an initially healthy-appearing premature infant.

    PubMed

    Edwards, Morven S; Popek, Edwina J; Wise, Brittany; Hatzenbuehler, Lindsay; Arunachalam, Athis R; Hair, Amy B

    2015-01-01

    The usual route of acquisition for intrauterine herpes simplex virus (HSV) infection is transplacental. We evaluated a premature infant with in utero acquisition of HSV resulting from ascending infection. Histopathologic evidence of chronic chorioamnionitis and positive staining with immunohistochemistry for HSV in the placenta and umbilical cord established the diagnosis. The clinical presentation was also of interest in that the infant was initially healthy appearing.

  13. Herpes simplex virus infections. New treatment approaches make early diagnosis even more important.

    PubMed

    Nadelman, C M; Newcomer, V D

    2000-03-01

    The herpes simplex viruses HSV-1 and HSV-2 cause problems for millions of people worldwide. Infections range from simple cold sores and fever blisters to severe central nervous system disorders. Development of effective antiviral medications has made prompt recognition important in primary care practice. Appropriate therapy can significantly reduce both medical and psychosocial ramifications of herpes infections and can greatly improve the quality of life for many patients.

  14. Detection and genotyping of herpes simplex virus types 1 and 2 by polymerase chain reaction.

    PubMed

    Lucotte, G; Bathelier, C; Lespiaux, V; Bali, C; Champenois, T

    1995-10-01

    A simple and rapid polymerase chain reaction (PCR) procedure was developed for simultaneous detection and typing of herpes simplex virus (HSV) types 1 and 2. It was possible to detect and type HSV using two primers pairs in a simultaneous double PCR reaction, where the type of HSV present was determined on the basis of an ethidium-bromide-stained band after agarose gel electrophoresis. This PCR assay was tested on about 500 clinical specimens.

  15. Simplex s={plus_minus}i excitations in {sup 141}Xe.

    SciTech Connect

    Urban, W.; Schulz, N.; Bentaleb, M.; Lubkiewicz, E.; Durell, J. L.; Leddy, M. J.; Jones, M. A.; Phillips, W. R.; Smith, A. G.; Varley, B. J.; Ahmad, I.; Morss, L. R.; Warsaw Univ.; Univ. Louis Pasteur; Univ. of Manchester

    2000-05-01

    Excited levels of {sup 141}Xe, populated in spontaneous fission of {sup 248}Cm, were studied by means of prompt {gamma}-ray spectroscopy, using the EUROGAMM2 array. Level scheme of {sup 141}Xe obtained in this work shows patterns characteristic of simplex symmetry with s = +i and s = -i bands present but low value of D{sub 0} moment indicates that octupole correlations in Xe isotopes are systematically lower than in Ba nuclei.

  16. Contributions of herpes simplex virus type 1 envelope proteins to entry by endocytosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Herpes simplex virus (HSV) proteins specifically required for endocytic entry but not direct penetration have not been identified. HSVs deleted of gE, gG, gI, gJ, gM, UL45, or Us9 entered cells via either pH-dependent or pH-independent endocytosis and were inactivated by mildly acidic pH. Thus, the ...

  17. Genome Sequence of the Anterograde-Spread-Defective Herpes Simplex Virus 1 Strain MacIntyre

    PubMed Central

    Tafuri, Yolanda R.; Parsons, Lance; Shreve, Jacob T.; Engel, Esteban A.; Enquist, L. W.

    2014-01-01

    We used paired-end Illumina deep sequencing and de novo assembly to determine the genome sequence of herpes simplex virus 1 (HSV-1) strain MacIntyre (aka McIntyre). The MacIntyre strain originated from the brain of a patient with lethal HSV encephalitis and has a unique limitation in its neuronal spread, moving solely in the retrograde direction. PMID:25395637

  18. Production of a fragment of glycoprotein G of herpes simplex virus type 2 and evaluation of its diagnostic potential

    PubMed Central

    Liu, Tao; Liu, Ji Feng; Yu, Hua; Si, Guo Jing; Hu, Jun; Li, Jun

    2015-01-01

    INTRODUCTION Herpes simplex virus type 2 (HSV-2) is the most common cause of genital herpes. Glycoprotein G (gG) is a prototype antigen for type-specific serodiagnosis distinguishing between HSV type 1 (HSV-1) and HSV-2 infections. As immunological diagnosis kits for accurate differentiation between HSV-1 and HSV-2 antibodies can be expensive, there is a need to develop a convenient, sensitive, specific and cost-effective serodiagnostic kit. METHODS We successfully expressed a fragment of gG comprising residues 321–580 of HSV-2 with histidine tag (gG321–580His) in a Bac-to-Bac baculovirus expression system, which had an antigenicity similar to its native counterpart. An indirect enzyme-linked immunosorbent assay (ELISA) was developed using gG321–580His as the diagnostic antigen and evaluated by comparison with a commercial HerpeSelect 2 ELISA immunoglobulin G kit as reference. RESULTS In testing 318 field serum samples, the diagnostic relative sensitivity and specificity of the developed gG321–580His-ELISA test in qualitative comparison with the commercial kit were 93.81% and 96.74%, respectively, and the accuracy was 94.65%. CONCLUSION The study indicates that gG321–580His has a high diagnostic potential for HSV-2 virus serodiagnosis in humans. PMID:25532518

  19. Analysis and Characterization of Herpes Simplex Virus After Its Persistance in a Lymphoblastoid Cell Line for 15 Months

    PubMed Central

    Roumillat, L. F.; Feorino, P. M.; Caplan, D. D.; Lukert, P. D.

    1980-01-01

    Infection of a human lymphoblastoid cell line (F-365 line containing Epstein-Barr viral capsid antigen, derived from an individual without overt signs of lymphoma, infectious mononucleosis, or leukemia) with herpes simplex virus (HSV), maintained and observed for 15 months, was characterized by the continuous production of infectious extracellular virus. By the 5th day postinfection 75% of the cells produced HSV antigen as detected by fluorescent antibody, and by the 10th day 90% did so; production continued through the 15th month. Only 11% of single isolated cells produced detectable infectious virus. HSV produced after the 3rd month formed smaller plaque in monolayer cell culture than did the parental virus. No antigenic or polypeptide change in the HSV was detected by crossed immunoelectrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis over the 15-month cultivation in F-365 cells. Cell susceptibility and HSV virulence did not appear to change. The HSV-lymphoblastoid cell culture provided a useful model in which to study long-term virus-cell interactions. ImagesFig. 3Fig. 4 PMID:6260656

  20. A role for heparan sulfate 3-O-sulfotransferase isoform 2 in herpes simplex virus type 1 entry and spread

    SciTech Connect

    O'Donnell, Christopher D.; Tiwari, Vaibhav; Oh, Myung-Jin; Shukla, Deepak . E-mail: dshukla@uic.edu

    2006-03-15

    Heparan sulfate (HS) 3-O-sulfotransferase isoform-2 (3-OST-2), which belongs to a family of enzymes capable of generating herpes simplex virus type-1 (HSV-1) entry and spread receptors, is predominantly expressed in human brain. Despite its unique expression pattern, the ability of 3-OST-2 to mediate HSV-1 entry and cell-to-cell fusion is not known. Our results demonstrate that expression of 3-OST-2 can render Chinese hamster ovary K1 (CHO-K1) cells susceptible to entry of wild-type and mutant strains of HSV-1. Evidence for generation of gD receptors by 3-OST-2 were suggested by gD-mediated interference assay and the ability of 3-OST-2-expressing CHO-K1 cells to preferentially bind HSV-1 gD, which could be reversed by prior treatment of cells with HS lyases (heparinases II/III). In addition, 3-OST-2-expressing CHO-K1 cells acquired the ability to fuse with cells-expressing HSV-1 glycoproteins, a phenomenon that mimics a way of viral spread in vivo. Demonstrating specificity, the cell fusion was inhibited by soluble 3-O-sulfated forms of HS, but not unmodified HS. Taken together, our results raise the possibility of a role of 3-OST-2 in the spread of HSV-1 infection in the brain.

  1. Topical application of polyethylenimine as a candidate for novel prophylactic therapeutics against genital herpes caused by herpes simplex virus.

    PubMed

    Hayashi, Kyoko; Onoue, Hiroki; Sasaki, Kohei; Lee, Jung-Bum; Kumar, Penmetcha K R; Gopinath, Subash C B; Maitani, Yoshie; Kai, Takashi; Hayashi, Toshimitsu

    2014-03-01

    Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) cause genital herpes, which can enhance the acquisition of human immunodeficiency virus. The development of anti-HSV agents with novel mechanisms of action is urgently required in the topical therapy of genital herpes. In this study, the in vitro and in vivo anti-HSV effects of Epomin SP-012(®), a highly cationic polyethylenimine, were evaluated. When the in vitro antiviral effects of SP-012 were assessed, this compound showed potent activity against HSV-1 and HSV-2. It inhibited the attachment of HSV-2 to host cells and cell-to-cell spread of infection in a concentration-dependent manner and exerted a virucidal effect. No SP-012-resistant HSV-2 was found when the virus was successively passaged in the presence of SP-012. In a mouse genital herpes model, topically administered SP-012 inhibited the progression of the disease caused by HSV infection. These data illustrate that SP-012 may be a novel class of HSV inhibitor that would be acceptable for long-term topical application.

  2. A Cationic Peptide, TAT-Cd0, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

    PubMed Central

    Jose, Gilbert G.; Larsen, Inna V.; Gauger, Joshua; Carballo, Erica; Stern, Rebecca; Brummel, Rachel; Brandt, Curtis R.

    2013-01-01

    Purpose. To test the in vivo activity of a peptide derived from the protein transducing domain of the human immunodeficiency virus (HIV) Tat protein, TAT-Cd0, in a murine herpes simplex type 1 (HSV-1) keratitis model. Methods. The efficacy of TAT-Cd0 was assessed in a postinfection treatment model with different concentrations (1 mg/mL, 0.1 mg/mL, 0.01 mg/mL) of the peptide in one of four delivery vehicles: artificial tears, PBS, methylcellulose, and aquaphor cream. Treatment began within 4 or 24 hours postinfection. Viral titers in the tear film were determined by plaque assay. Results. TAT-Cd0 reduced the severity of keratitis in all of the delivery vehicles tested when treatment started, 4 hours postinfection. Peptide in the tears or PBS delivery vehicle had the most significant reduction in disease severity and delayed the onset of vascularization and stromal keratitis. The percentage of mice presenting with disease was also significantly reduced and viral titers were reduced by 1 log at 24 hours postinfection in mice treated with 1 mg/mL TAT-Cd0, suggesting that inhibiting replication early is sufficient to achieve clinical effects. Lower concentrations were not effective and delaying treatment by 24 hours was also not effective. Conclusions. This study shows that TAT-Cd0 is an effective antiviral against HSV-1 strain KOS when applied shortly postinfection and that aqueous-based formulations are more suitable. PMID:23341013

  3. A Strategy for O-Glycoproteomics of Enveloped Viruses—the O-Glycoproteome of Herpes Simplex Virus Type 1

    PubMed Central

    Bagdonaite, Ieva; Nordén, Rickard; Joshi, Hiren J.; Dabelsteen, Sally; Nyström, Kristina; Vakhrushev, Sergey Y.; Olofsson, Sigvard; Wandall, Hans H.

    2015-01-01

    Glycosylation of viral envelope proteins is important for infectivity and interaction with host immunity, however, our current knowledge of the functions of glycosylation is largely limited to N-glycosylation because it is difficult to predict and identify site-specific O-glycosylation. Here, we present a novel proteome-wide discovery strategy for O-glycosylation sites on viral envelope proteins using herpes simplex virus type 1 (HSV-1) as a model. We identified 74 O-linked glycosylation sites on 8 out of the 12 HSV-1 envelope proteins. Two of the identified glycosites found in glycoprotein B were previously implicated in virus attachment to immune cells. We show that HSV-1 infection distorts the secretory pathway and that infected cells accumulate glycoproteins with truncated O-glycans, nonetheless retaining the ability to elongate most of the surface glycans. With the use of precise gene editing, we further demonstrate that elongated O-glycans are essential for HSV-1 in human HaCaT keratinocytes, where HSV-1 produced markedly lower viral titers in HaCaT with abrogated O-glycans compared to the isogenic counterpart with normal O-glycans. The roles of O-linked glycosylation for viral entry, formation, secretion, and immune recognition are poorly understood, and the O-glycoproteomics strategy presented here now opens for unbiased discovery on all enveloped viruses. PMID:25830354

  4. Virostatic potential of micro-nano filopodia-like ZnO structures against herpes simplex virus-1

    PubMed Central

    Mishra, Yogendra Kumar; Adelung, Rainer; Roehl, Claudia; Shukla, Deepak; Spors, Frank; Tiwari, Vaibhav

    2011-01-01

    Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell induced filopodia. These MNSs were predicted to target the virus to compete for its binding to cellular HS through their partially negatively charged oxygen vacancies on their nanoscopic spikes, to affect viral entry and subsequent spread. Our results demonstrate that the partially negatively charged ZnO-MNSs efficiently trap the virions via a novel virostatic mechanism rendering them unable to enter into human corneal fibroblasts-a natural target cell for HSV-1 infection. The anti-HSV-1 activity of ZnO MNSs was drastically enhanced after creating additional oxygen vacancies under UV-light illumination. Our results provide a novel insight into the significance of ZnO MNSs as the potent HSV-1 inhibitor and rationalize their development as a novel topical agent for the prevention of HSV-1 infection. PMID:21893101

  5. Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector.

    PubMed

    Taylor, Travis J; Diaz, Fernando; Colgrove, Robert C; Bernard, Kristen A; DeLuca, Neal A; Whelan, Sean P J; Knipe, David M

    2016-09-01

    West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8(+) T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus. PMID:27336950

  6. Antigenic cross-reactions among herpes simplex virus types 1 and 2, Epstein-Barr virus, and cytomegalovirus.

    PubMed Central

    Balachandran, N; Oba, D E; Hutt-Fletcher, L M

    1987-01-01

    Polyvalent rabbit antisera against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), and Epstein-Barr virus (EBV), monospecific antisera against affinity-purified HSV-2 glycoproteins gB and gG, and a panel of monoclonal antibodies against HSV and EBV proteins were used to analyze cross-reactive molecules in cells infected with the four herpesviruses. A combination of immunoprecipitation and Western blotting with these reagents was used to determine that all four viruses coded for a glycoprotein that cross-reacted with HSV-1 gB. CMV coded for proteins that cross-reacted with HSV-2 gC, gD, and gE. Both CMV and EBV coded for proteins that cross-reacted with HSV-2 gG. Antigenic counterparts to the p45 nucleocapsid protein of HSV-2 were present in HSV-1 and CMV, and counterparts of the major DNA-binding protein and the ribonucleotide reductase of HSV-1 were present in all the viruses. The EBV virion glycoprotein gp85 was immunoprecipitated by antisera to HSV-1, HSV-2, and CMV. Antisera to CMV and EBV neutralized the infectivity of both HSV-1 and HSV-2 at high concentrations. This suggests that cross-reactivity between these four human herpesviruses may have pathogenic as well as evolutionary significance. Images PMID:3029407

  7. Monitoring of bystander effect of herpes simplex virus thymidine kinase/acyclovir system using fluorescence resonance energy transfer technique.

    PubMed

    Xiong, Tao; Li, Yongjun; Ni, Fenge; Zhang, Feng

    2012-02-01

    Cytotoxic gene therapy mediated by gene transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by acyclovir (ACV) treatment has been reported to inhibit malignant tumor growth in a variety of studies. The magnitude of "bystander effect" is an essential factor for this anti-tumor approach in vivo. However, the mechanism by which HSV-tk/ACV brings "bystander effect" is poorly understood. In this report, the plasmid CD3 (ECFP-CRS-DsRed) and TK-GFP were transferred to the human adenoid cystic carcinoma line ACC-M cell line. The CD3-expressing cells apoptosis was monitored using fluorescence resonance energy transfer (FRET) technique. First, CD3 and TK-GFP co-expressing ACC-M cells apoptosis was monitored using FRET technique. The apoptosis was induced by ACV and initiated by caspase3. The FRET efficient was remarkably decreased and then disappeared during cellular apoptosis, which indicated that the TK-GFP expressing ACC-M cells apoptosis, induced by ACV, was via a caspase3-dependent pathway. Secondly, CD3 and TK-GFP mixed expressing ACC-M cells apoptosis, induced by ACV, were monitored using FRET technique. The apoptotic phenomena appeared in the CD3-expressing ACC-M cells. The results show that HSV-tk/ACV system killed ACC-M cells using its bystander effect. These results confirm that HSV-tk/ACV system is potential for cancer gene therapy.

  8. The nucleotide sequence of an equine herpesvirus 4 gene homologue of the herpes simplex virus 1 glycoprotein H gene.

    PubMed

    Nicolson, L; Cullinane, A A; Onions, D E

    1990-08-01

    The equine herpesvirus 4 (EHV-4) gene glycoprotein H (gH) gene homologue was localized by virtue of the conserved genomic position of this gene throughout members of the herpesvirus family. The gene maps immediately downstream of the thymidine kinase gene at approximately 0.49 to 0.51 map units within genomic fragment BamH1 C. The EHV-4 gH primary translation product is predicted to be a polypeptide of Mr 94,100, 855 amino acids long, which possesses features characteristic of a membrane glycoprotein, namely an N-terminal signal sequence, a large hydrophilic domain containing 11 putative N-linked glycosylation sites, a C-terminal transmembrane domain, and a charged cytoplasmic tail. Comparison to other herpesvirus glycoproteins revealed identities of 85%, 26% and 32% with the gH counterparts of the alphaherpesviruses EHV-1, herpes simplex virus 1 and varicella-zoster virus, respectively, and of 17% and 18% with those of human cytomegalovirus, herpesvirus saimiri and Epstein-Barr virus. The EHV-4 gH exhibits features previously reported to be conserved throughout the gH polypeptides of herpesviruses of all three subgroups. A region of direct repeat elements and a possible origin of DNA replication are located immediately downstream of the gH gene. PMID:2167933

  9. Muscle-specific promoters may be necessary for adeno-associated virus-mediated gene transfer in the treatment of muscular dystrophies.

    PubMed

    Cordier, L; Gao, G P; Hack, A A; McNally, E M; Wilson, J M; Chirmule, N; Sweeney, H L

    2001-01-20

    Recombinant adeno-associated virus (rAAV) vectors allow efficient gene transfer and expression in the muscle; therefore, rAAVs represent a potential gene therapy vector for muscular dystrophies. For further investigations, we used a mouse muscular dystrophy model (gsg(-/-) mice) gamma-sarcoglycan, a subunit of the dystrophin-glycoprotein complex, is missing. gsg(-/-) mice develop progressive dystrophy representative of a severe human phenotype disease. We previously showed high levels and stable expression of gamma-sarcoglycan in myofibers after direct muscle injection into gsg(-/-) mice of a recombinant AAV vector (AAV.dMCK.gSG) carrying the gamma-sarcoglycan cDNA driven by a muscle-specific promoter (truncated version of muscle creatine kinase). Here, we show that when gamma-sarcoglycan expression is driven by the ubiquitous cytomegalovirus (CMV) promoter (AAV.CMV.gSG), lower levels of transgene expression are observed and are associated with a humoral response to gamma-sarcoglycan. When using an rAAV vector, expressing the highly immunogenic product gamma-galactosidase under the CMV promoter (AAV.CMV.LacZ), we measured a strong cellular and humoral immune response to the transgene after intramuscular injection into gsg(-/-) mice. This study suggests that restriction of transgene expression to the muscle is an important criterion for the treatment of muscular dystrophies and will aid in the design of protocols for gene therapy.

  10. Inhibitory activity of Melissa officinalis L. extract on Herpes simplex virus type 2 replication.

    PubMed

    Mazzanti, G; Battinelli, L; Pompeo, C; Serrilli, A M; Rossi, R; Sauzullo, I; Mengoni, F; Vullo, V

    2008-01-01

    Melissa officinalis L. (Lamiaceae) (lemon balm) is used in folk medicine for nervous complaints, lower abdominal disorders and, more recently, for treating Herpes simplex lesions. In this work the antiviral activity of a hydroalcoholic extract of lemon balm leaves against the Herpes simplex virus type 2 (HSV-2) was assessed by the cytopathic effect inhibition assay on Vero cells (ATCC CCL-81), in comparison with acyclovir. The cytotoxicity of the extract on Vero cells was previously tested by evaluating the cellular death and was confirmed by the Trypan blue test. Lemon balm showed to reduce the cytopathic effect of HSV-2 on Vero cells, in the range of non-toxic concentrations of 0.025-1 mg mL(-1) (with reference to the starting crude herbal material). The maximum inhibiting effect (60%) was obtained with 0.5 mg mL(-1). The viral binding assay showed that the extract does not prevent the entry of HSV-2 in the cells, thus suggesting a mechanism of action subsequent to the penetration of the virus in the cell. The extract was also chemically characterised by NMR and HPLC analysis; it showed to contain cinnamic acid-like compounds, mainly rosmarinic acid (4.1% w/w). Our experiments support the use of lemon balm for treating Herpes simplex lesions and encourage clinical trials on this medicinal plant. PMID:19023806

  11. Multifunction extension of simplex optimization method for mutual information-based registration of ultrasound volumes

    NASA Astrophysics Data System (ADS)

    Zagrodsky, Vladimir; Shekhar, Raj; Cornhill, J. Fredrick

    2001-07-01

    Mutual information has been demonstrated to be an accurate and reliable criterion function to perform registration of medical data. Due to speckle noise, ultrasound volumes do not provide a smooth mutual information function. Consequently the optimization technique used must be robust enough to avoid local maxima and converge on the desired global maximum eventually. While the well-known downhill simplex optimization uses a single criterion function, our extension to multi-function optimization uses three criterion functions, namely mutual information computed at three levels of intensity quantization and hence three degrees of noise suppression. Registration was performed with rigid as well as simple non-rigid transformation modes for real-time 3D ultrasound datasets of the left ventricle. Pairs of frames corresponding to the most stationary end- diastolic cardiac phase were chosen, and an initial misalignment was artificially introduced between them. The multi-function simplex optimization reduced the failure rate by a factor of two in comparison to the standard simplex optimization, while the average accuracy for the successful cases was unchanged. A more robust registration resulted form the parallel use of criterion functions. The additional computational cost was negligible, as each of the three implementations of the mutual information used the same joint histogram and required no extra spatial transformation.

  12. Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure

    PubMed Central

    Poley, Rachel A.; Snowdon, Jaime F.; Howes, Daniel W.

    2011-01-01

    Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis. Design. Observation of a single patient. Setting. Intensive care unit of a tertiary care university teaching hospital in Canada. Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome. Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes. Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death. Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated. PMID:24826316

  13. Viability and antigenicity of anisakis simplex after conventional and microwave heating at fixed temperatures.

    PubMed

    Vidaček, Sanja; De Las Heras, Cristina; Solas, Maria Teresa; García, Maria Luisa; Mendizábal, Angel; Tejada, Margarita

    2011-12-01

    Inactivation of parasites in food by microwave treatment may vary due to differences in the characteristics of microwave ovens and food properties. Microwave treatment in standard domestic ovens results in hot and cold spots, and the microwaves do not penetrate all areas of the samples depending on the thickness, which makes it difficult to compare microwave with conventional heat treatments. The viability of Anisakis simplex (isolated larvae and infected fish muscle) heated in a microwave oven with precise temperature control was compared with that of larvae heated in a water bath to investigate any additional effect of the microwaves. At a given temperature, less time was required to kill the larvae by microwaves than by heated water. Microwave treatment killed A. simplex larvae faster than did conventional cooking when the microwaves fully penetrated the samples and resulted in fewer changes in the fish muscle. However, the heat-stable allergen Ani s 4 was detected by immunohistochemistry in the fish muscle after both heat treatments, even at 70°C, suggesting that Ani s 4 allergens were released from the larvae into the surrounding tissue and that the tissues retained their allergenicity even after the larvae were killed by both heat treatments. Thus, microwave cooking will not render fish safe for individuals already sensitized to A. simplex heat-resistant allergens. PMID:22186053

  14. Inhibitory activity of Melissa officinalis L. extract on Herpes simplex virus type 2 replication.

    PubMed

    Mazzanti, G; Battinelli, L; Pompeo, C; Serrilli, A M; Rossi, R; Sauzullo, I; Mengoni, F; Vullo, V

    2008-01-01

    Melissa officinalis L. (Lamiaceae) (lemon balm) is used in folk medicine for nervous complaints, lower abdominal disorders and, more recently, for treating Herpes simplex lesions. In this work the antiviral activity of a hydroalcoholic extract of lemon balm leaves against the Herpes simplex virus type 2 (HSV-2) was assessed by the cytopathic effect inhibition assay on Vero cells (ATCC CCL-81), in comparison with acyclovir. The cytotoxicity of the extract on Vero cells was previously tested by evaluating the cellular death and was confirmed by the Trypan blue test. Lemon balm showed to reduce the cytopathic effect of HSV-2 on Vero cells, in the range of non-toxic concentrations of 0.025-1 mg mL(-1) (with reference to the starting crude herbal material). The maximum inhibiting effect (60%) was obtained with 0.5 mg mL(-1). The viral binding assay showed that the extract does not prevent the entry of HSV-2 in the cells, thus suggesting a mechanism of action subsequent to the penetration of the virus in the cell. The extract was also chemically characterised by NMR and HPLC analysis; it showed to contain cinnamic acid-like compounds, mainly rosmarinic acid (4.1% w/w). Our experiments support the use of lemon balm for treating Herpes simplex lesions and encourage clinical trials on this medicinal plant.

  15. Developmental stages and fecundity of Lepeophtheirus simplex (Copepoda: Caligidae) parasitic on bullseye puffer fish (Sphoeroides annulatus).

    PubMed

    Neptali Morales-Serna, Francisco; Rivas-Salas, Ana Ines; Gomez, Samuel; Fajer-Avila, Emma Josefina

    2015-01-01

    Lepeophtheirus simplex Ho, Gómez et Fajer-Avila, 2001 is a parasite of Sphoeroides annulatus (Jenyns), an economically important fish species, with potential for aquaculture, in northwestern Mexico. The goal of this study was to describe the developmental stages under experimental conditions and seasonal fecundity of this parasite on wild fish. There are two naupliar, one copepodid, two chalimus and two pre-adult stages preceding the adult of L. simplex. The results support previous findings, which point out that the life cycle of the caligid copepods includes only six post-naupliar stages. The generation time from egg extrusion to adult for L. simplex was approximately 10 days at 22 °C. The body length of the ovigerous females ranged between 2.2 and 4.1 mm, and its fecundity between 12 and 36 eggs per string. Fecundity was negatively correlated with the egg size and positively correlated with the egg string length. Our data did not reveal significant differences in fecundity among sampling months, but ovigerous females were significantly larger in March (when water temperature was 22 °C) than in June and July (when water temperature was 30 °C). To some extent, our fecundity results contrast with those found in species of sea lice from higher latitudes. Undoubtedly, biological information on different species of sea lice from different environmental conditions will enhance our understanding of their infection strategies and will be valuable, given the increasing interest in marine fish farming in Mexico. PMID:25960548

  16. Valaciclovir versus aciclovir for the treatment of primary genital herpes simplex: a cost analysis.

    PubMed

    Pinder, Melissa; Wright, Alison

    2015-11-01

    The current guidelines for the treatment of primary herpes simplex in the Genito-urinary department in Sheffield Teaching Hospitals NHS Foundation Trust, recommend valaciclovir as a first-line medication. This is a prodrug of aciclovir, which has been used for many years as a treatment for primary herpes simplex virus. The basis of the recommendation largely relates to valaciclovir being more bioavailable than aciclovir. However, there is no evidence to suggest this has an effect on overall outcome with regard to symptom control and viral shedding. The purpose of the service evaluation was to discover if significant cost savings could be made by changing the prescribing policy to make aciclovir the drug of choice for primary herpes simplex virus. Based on 160 patients receiving valaciclovir (500 mg BD) during April 2013 and March 2014, if they had been treated with aciclovir (400 mg TDS) instead, a saving of £828.80 (66% reduction) could have been made.

  17. Diagnosis of Herpes Simplex Encephalitis by ELISA Using Antipeptide Antibodies Against Type-Common Epitopes of Glycoprotein B of Herpes Simplex Viruses.

    PubMed

    Bhullar, Shradha S; Chandak, Nitin H; Baheti, Neeraj N; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F; Kashyap, Rajpal S

    2016-01-01

    Herpes simplex encephalitis (HSE) represents one of the most severe infectious diseases of the central nervous system (CNS). As effective antiviral drugs are available, an early, rapid, and reliable diagnosis has become important. The objective of this article was to develop a sensitive ELISA protocol for herpes simplex viruses (HSV) antigen detection and quantitation by assessing the usefulness of antipeptide antibodies against potential peptides of HSV glycoprotein B (gB). A total of 180 cerebrospinal fluid (CSF) samples of HSE and non-HSE patients were analyzed using a panel of antipeptide antibodies against synthetic peptides of HSV glycoprotein gB. The cases of confirmed and suspected HSE showed 80% and 51% positivity for antipeptide against synthetic peptide QLHDLRF and 77% and 53% positivity for antipeptide against synthetic peptide MKALYPLTT, respectively for the detection of HSV antigen in CSF. The concentration of HSV antigen was found to be higher in confirmed HSE as compared to suspected HSE group and the viral load correlated well with antigen concentration obtained using the two antipeptides in CSF of confirmed HSE group. This is the first article describing the use of antibodies obtained against synthetic peptides derived from HSV in diagnostics of HSE using patients' CSF samples.

  18. A cytomegalovirus protein with properties of herpes simplex virus ICP8: partial purification of the polypeptide and map position of the gene.

    PubMed Central

    Kemble, G W; McCormick, A L; Pereira, L; Mocarski, E S

    1987-01-01

    We demonstrated the presence of a single-stranded DNA-binding protein in human cytomegalovirus (CMV)-infected cells with properties analogous to those of herpes simplex virus (HSV) ICP8. Using monoclonal antibody specific for the CMV protein, we analyzed its fluorescence pattern and time of synthesis, mapped the gene encoding it by using a lambda gt11 library of CMV DNA fragments, and monitored its purification by phosphocellulose and DNA-Sepharose chromatography. In all characteristics we examined, the CMV protein behaved analogously to HSV ICP8. Our results are consistent with a functional role of CMV ICP8 in viral replication that is similar to that of HSV ICP8 and with the evolutionary conservation of the gene of interest in two divergent herpesviruses. Images PMID:3041036

  19. Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase.

    PubMed

    Visalli, Robert J; Ziobrowski, Hannah; Badri, Kameswara R; He, Johnny J; Zhang, Xiugen; Arumugam, Sri Ranjini; Zhao, Hua

    2015-08-15

    Betulinic acid (1) has been modified to ionic derivatives (2-5) to improve its water solubility and biological activities. The binding properties of these derivatives with respect to human serum albumin (HSA) was examined and found to be similar to current anti-HIV drugs. These compounds did not inhibit HIV reverse transcriptase, however, 1, 2 and 5 inhibited herpes simplex type 2 (HSV-2) replication at concentrations similar to those reported for acyclovir (IC50 ∼ 0.1-10 μM) and with minimal cellular cytotoxicity. IC50 values for antiviral activity against HSV-2 186 were 1.6, 0.6, 0.9, 7.2, and 0.9 μM for compounds 1-5, respectively.

  20. The Us3 Protein of Herpes Simplex Virus 1 Inhibits T Cell Signaling by Confining Linker for Activation of T Cells (LAT) Activation via TRAF6 Protein*

    PubMed Central

    Yang, Yin; Wu, Songfang; Wang, Yu; Pan, Shuang; Lan, Bei; Liu, Yaohui; Zhang, Liming; Leng, Qianli; Chen, Da; Zhang, Cuizhu; He, Bin; Cao, Youjia

    2015-01-01

    Herpes simplex virus 1 (HSV-1) is the most prevalent human virus and causes global morbidity because the virus is able to infect multiple cell types. Remarkably, HSV infection switches between lytic and latent cycles, where T cells play a critical role. However, the precise way of virus-host interactions is incompletely understood. Here we report that HSV-1 productively infected Jurkat T-cells and inhibited antigen-induced T cell receptor activation. We discovered that HSV-1-encoded Us3 protein interrupted TCR signaling and interleukin-2 production by inactivation of the linker for activation of T cells. This study unveils a mechanism by which HSV-1 intrudes into early events of TCR-mediated cell signaling and may provide novel insights into HSV infection, during which the virus escapes from host immune surveillance. PMID:25907557

  1. Characterization of virus obtained from MDBK cells persistently infected with a variant of herpes simplex virus type 1 strain MP [HSV-1(MP)].

    PubMed

    Bartoletti, A M; Tognon, M; Manservigi, R; Mannini-Palenzona, A

    1985-03-01

    Virus clones which express glycoprotein gC (gC+) were obtained from two persistently infected (p.i.) MDBK cell lines which had been independently established by infection with HSV-1(MP)10311, a gC- syncytial (syn) variant of herpes simplex virus type 1 strain MP [HSV-1(MP)]. The gC+ revertants were syn in MDBK, HEp-2, and Vero cell lines and in primary human fibroblasts; this offers further evidence that glycoprotein gC does not inhibit cell fusion. The gC+ revertants represented from 70 to 100 percent of the virions present in the virus populations examined, thus suggesting a possible selective advantage of the gC+ revertants in this system of persistent infection.

  2. Nonthermal Dielectric Barrier Discharge (DBD) Plasma Suppresses Herpes Simplex Virus Type 1 (HSV-1) Replication in Corneal Epithelium

    PubMed Central

    Alekseev, Oleg; Donovan, Kelly; Limonnik, Vladimir; Azizkhan-Clifford, Jane

    2014-01-01

    Purpose Herpes keratitis (HK) is the leading cause of cornea-derived and infection-associated blindness in the developed world. Despite the availability of effective antivirals, some patients develop refractory disease, drug-resistant infection, and topical toxicity. A nonpharmaceutical treatment modality may offer a unique advantage in the management of such cases. This study investigated the antiviral effect of nonthermal dielectric barrier discharge (DBD) plasma, a partially ionized gas that can be applied to organic substances to produce various biological effects. Methods Human corneal epithelial cells and explanted corneas were infected with herpes simplex virus type 1 (HSV-1) and exposed to culture medium treated with nonthermal DBD plasma. The extent of infection was measured by plaque assay, quantitative PCR, and Western blot. Corneal toxicity assessment was performed with fluorescein staining, histologic examination, and 8-OHdG detection. Results Application of DBD plasma–treated medium to human corneal epithelial cells and explanted corneas produced a dose-dependent reduction of the cytopathic effect, viral genome replication, and the overall production of infectious viral progeny. Toxicity studies showed lack of detrimental effects in explanted human corneas. Conclusions Nonthermal DBD plasma substantially suppresses corneal HSV-1 infection in vitro and ex vivo without causing pronounced toxicity. Translational Relevance Nonthermal plasma is a versatile tool that holds great biomedical potential for ophthalmology, where it is being investigated for wound healing and sterilization and is already in use for ocular microsurgery. The anti-HSV-1 activity of DBD plasma demonstrated here could be directly translated to the clinic for use against drug-resistant herpes keratitis. PMID:24757592

  3. Herpes simplex encephalitis is linked with selective mitochondrial damage; a post-mortem and in vitro study.

    PubMed

    Wnęk, Małgorzata; Ressel, Lorenzo; Ricci, Emanuele; Rodriguez-Martinez, Carmen; Guerrero, Julio Cesar Villalvazo; Ismail, Zarini; Smith, Colin; Kipar, Anja; Sodeik, Beate; Chinnery, Patrick F; Solomon, Tom; Griffiths, Michael J

    2016-09-01

    Herpes simplex virus type-1 (HSV-1) encephalitis (HSE) is the most commonly diagnosed cause of viral encephalitis in western countries. Despite antiviral treatment, HSE remains a devastating disease with high morbidity and mortality. Improved understanding of pathogenesis may lead to more effective therapies. Mitochondrial damage has been reported during HSV infection in vitro. However, whether it occurs in the human brain and whether this contributes to the pathogenesis has not been fully explored. Minocycline, an antibiotic, has been reported to protect mitochondria and limit brain damage. Minocycline has not been studied in HSV infection. In the first genome-wide transcriptomic study of post-mortem human HSE brain tissue, we demonstrated a highly preferential reduction in mitochondrial genome (MtDNA) encoded transcripts in HSE cases (n = 3) compared to controls (n = 5). Brain tissue exhibited a significant inverse correlation for immunostaining between cytochrome c oxidase subunit 1 (CO1), a MtDNA encoded enzyme subunit, and HSV-1; with lower abundance for mitochondrial protein in regions where HSV-1 was abundant. Preferential loss of mitochondrial function, among MtDNA encoded components, was confirmed using an in vitro primary human astrocyte HSV-1 infection model. Dysfunction of cytochrome c oxidase (CO), a mitochondrial enzyme composed predominantly of MtDNA encoded subunits, preceded that of succinate dehydrogenase (composed entirely of nuclear encoded subunits). Minocycline treated astrocytes exhibited higher CO1 transcript abundance, sustained CO activity and cell viability compared to non-treated astrocytes. Based on observations from HSE patient tissue, this study highlights mitochondrial damage as a critical and early event during HSV-1 infection. We demonstrate minocycline preserves mitochondrial function and cell viability during HSV-1 infection. Minocycline, and mitochondrial protection, offers a novel adjunctive therapeutic approach for

  4. Herpes simplex encephalitis is linked with selective mitochondrial damage; a post-mortem and in vitro study.

    PubMed

    Wnęk, Małgorzata; Ressel, Lorenzo; Ricci, Emanuele; Rodriguez-Martinez, Carmen; Guerrero, Julio Cesar Villalvazo; Ismail, Zarini; Smith, Colin; Kipar, Anja; Sodeik, Beate; Chinnery, Patrick F; Solomon, Tom; Griffiths, Michael J

    2016-09-01

    Herpes simplex virus type-1 (HSV-1) encephalitis (HSE) is the most commonly diagnosed cause of viral encephalitis in western countries. Despite antiviral treatment, HSE remains a devastating disease with high morbidity and mortality. Improved understanding of pathogenesis may lead to more effective therapies. Mitochondrial damage has been reported during HSV infection in vitro. However, whether it occurs in the human brain and whether this contributes to the pathogenesis has not been fully explored. Minocycline, an antibiotic, has been reported to protect mitochondria and limit brain damage. Minocycline has not been studied in HSV infection. In the first genome-wide transcriptomic study of post-mortem human HSE brain tissue, we demonstrated a highly preferential reduction in mitochondrial genome (MtDNA) encoded transcripts in HSE cases (n = 3) compared to controls (n = 5). Brain tissue exhibited a significant inverse correlation for immunostaining between cytochrome c oxidase subunit 1 (CO1), a MtDNA encoded enzyme subunit, and HSV-1; with lower abundance for mitochondrial protein in regions where HSV-1 was abundant. Preferential loss of mitochondrial function, among MtDNA encoded components, was confirmed using an in vitro primary human astrocyte HSV-1 infection model. Dysfunction of cytochrome c oxidase (CO), a mitochondrial enzyme composed predominantly of MtDNA encoded subunits, preceded that of succinate dehydrogenase (composed entirely of nuclear encoded subunits). Minocycline treated astrocytes exhibited higher CO1 transcript abundance, sustained CO activity and cell viability compared to non-treated astrocytes. Based on observations from HSE patient tissue, this study highlights mitochondrial damage as a critical and early event during HSV-1 infection. We demonstrate minocycline preserves mitochondrial function and cell viability during HSV-1 infection. Minocycline, and mitochondrial protection, offers a novel adjunctive therapeutic approach for

  5. [A case of an allergic reaction due to Anisakis simplex possibly after the ingestion of squid--successful detection of four A. simplex allergens, Ani s 1, Ani s 2, Ani s 12 and troponin C-like protein].

    PubMed

    Iijima, Shigeruko; Moriyama, Tatsuya; Ichikawa, Hidetaka; Kobayashi, Yukihiro; Shiomi, Kazuo

    2012-08-01

    A 62-year-old man ingested dressed salmon and its roe (ikura) and grilled mackerel and one hour later further ingested raw tuna and squid as an evening meal at a bar. Soon after the ingestion of raw seafood, he showed wheals, loss of consciousness and low blood pressure. Specific serum IgE to the nematode Anisakis simplex was positive but those to some seafoods were negative. Moreover, a skin prick test using the crude extract was positive for A. simplex but negative for the seafoods, which he ingested on the day of the above episode. When the A. simplex extract was analyzed by IgE-binding immunoblot analysis using the patient serum, two highly intense protein bands were recognized at 18 and 17 kDa, one intense band at 35 kDa and two weak bands at 28 and 26 kDa. ELISA with 11 natural or recombinant A. simplex allergens (Ani s 1-6, 8, 9, 11 and 12 and troponin C-like protein) showed that the patient serum strongly reacted to Ani s 1 and Ani s 12 and weakly to Ani s 2 and troponin C-like protein. Based on these results, he was diagnosed as IgE-mediated A. simplex allergy due to four allergens (Ani s 1, Ani s 2, Ani s 12 and troponin C-like protein), possibly infested in the raw squid which he had ingested just before manifestation of allergic reactions.

  6. Infection of vascular endothelial cells with herpes simplex virus enhances tissue factor activity and reduces thrombomodulin expression.

    PubMed Central

    Key, N S; Vercellotti, G M; Winkelmann, J C; Moldow, C F; Goodman, J L; Esmon, N L; Esmon, C T; Jacob, H S

    1990-01-01

    Latent infection of vascular cells with herpes-viruses may play a pathogenic role in the development of human atherosclerosis. In a previous study, we found that cultured human umbilical vein endothelial cells (HUVECs) infected with herpes simplex virus 1 (HSV-1) became procoagulant, exemplified both by their enhanced assembly of the prothrombinase complex and by their inability to reduce adhesion of platelets. We now report two further procoagulant consequences of endothelial HSV infection: loss of surface thrombomodulin (TM) activity and induction of synthesis of tissue factor. Within 4 hr of infection of HUVECs, TM activity measured by thrombin-dependent protein C activation declined 21 +/- 3% (P less than 0.05) and by 18 hr, 48 +/- 5% (P less than 0.001). Similar significant TM decrements accompanied infection of bovine aortic endothelial cells. Identical TM loss was induced with HSV-2 infection but not with adenovirus infection. Decreased surface expression of TM antigen (measured by the specific binding of a polyclonal antibody to bovine TM) closely paralleled the loss of TM activity. As examined by Northern blotting, these losses apparently reflected rapid onset (within 4 hr of HSV infection) loss of mRNA for TM. In contrast, HSV infection induced a viral-dose-dependent increase in synthesis of tissue factor protein, adding to the procoagulant state. The results indicate that loss of endothelial protein-synthetic capacity is not a universal effect of HSV infection. We suggest that the procoagulant state induced by reduction in TM activity and amplified tissue factor activity accompanying HSV infection of endothelium could contribute to deposition of thrombi on atherosclerotic plaques and to the "coagulant-necrosis" state that characterizes HSV-infected mucocutaneous lesions. Images PMID:2169619

  7. Computational rationale for the selective inhibition of the herpes simplex virus type 1 uracil-DNA glycosylase enzyme.

    PubMed

    Hendricks, Umraan; Crous, Werner; Naidoo, Kevin J

    2014-12-22

    The herpes simplex virus uracil-DNA glycosylase (hsvUNG) enzyme is responsible for the reactivation of the virus from latency and efficient viral replication in nerve tissue. The lack of uracil-DNA glycosylase enzyme in human neurons and the continuous deamination of cytosine create an environment where the presence of viral uracil-DNA glycosylase is a necessity for the proliferation of the virus. A series of 6-(4-alkylanilino)-uracil inhibitors has been developed that selectively and strongly binds to the hsvUNG enzyme while weakly binding to human uracil-DNA glycosylase (hUNG). Here, by using a combination of sequence and structural comparisons between the two enzymes along with free energy of binding computations and principal component analysis of the ligands, we investigate and rationalize the inhibitory effect of the 6-(4-alkylanilino)-uracil series as a function of alkyl chain length on the hsvUNG. The results of these computations corroborate the experimental finding that the inhibitor with an octyl aliphatic chain selectively binds hsvUNG best. More importantly we find that 6-(4-octylanilino)-uracil's selective inhibition of hsvUNG over hUNG is due to the combination of the solution preconfigured bent conformation of that specific chain length and the position of HIS92 (absent in hUNG) just outside hsvUNG's hydrophobic gorge lying adjacent to its uracil binding pocket. The similarities between the uracil binding pockets in hsvUNG and hUNG obfuscate an understanding of the preferential inhibition of the virus enzyme. However, the differences in the enzymes' shallow hydrophobic grooves adjacent to the binding pockets, such as the gorge we identify here, rationalizes 6-(4-alkylanilino)-uracil with an octyl chain length as an excellent pharmacophore template for hsvUNG inhibitor design.

  8. Chlamydial Pre-Infection Protects from Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model.

    PubMed

    Slade, Jessica; Hall, Jennifer V; Kintner, Jennifer; Schoborg, Robert V

    2016-01-01

    Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singly-infected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans. PMID:26726882

  9. Chlamydial Pre-Infection Protects from Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model

    PubMed Central

    Slade, Jessica; Hall, Jennifer V.; Kintner, Jennifer; Schoborg, Robert V.

    2016-01-01

    Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singly-infected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans. PMID:26726882

  10. Glycoprotein G of herpes simplex virus 2 as a novel vaccine antigen for immunity to genital and neurological disease.

    PubMed

    Görander, Staffan; Harandi, Ali M; Lindqvist, Madelene; Bergström, Tomas; Liljeqvist, Jan-Åke

    2012-07-01

    The envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-γ) response by splenic CD4(+) T cells upon antigen restimulation in vitro and in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials. PMID:22553328

  11. Glycoprotein G of Herpes Simplex Virus 2 as a Novel Vaccine Antigen for Immunity to Genital and Neurological Disease

    PubMed Central

    Görander, Staffan; Harandi, Ali M.; Lindqvist, Madelene; Bergström, Tomas

    2012-01-01

    The envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-γ) response by splenic CD4+ T cells upon antigen restimulation in vitro and in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials. PMID:22553328

  12. Physical mapping of the herpes simplex virus type 2 nuc- lesion affecting alkaline exonuclease activity by using herpes simplex virus type 1 deletion clones.

    PubMed

    Wathen, M W; Hay, J

    1984-07-01

    The nuc- lesion affecting alkaline exonuclease activity in the herpes simplex virus type 2 (HSV-2) mutant ts1348 had previously been mapped to the EcoRI-D restriction enzyme fragment of HSV-1. Eight clones with deletions representing most of HSV-1 EcoRI fragment D were selected with lambda gtWES hybrids. These clones were tested for their ability to rescue the alkaline exonuclease activity of HSV-2 nuc- ts1348 virus. The sequences colinear with the HSV-2 nuc- lesion were found to map between 0.169 and 0.174 map units on the HSV-1 Patton genome, representing an 0.8-kilobase-pair region that is 12.9 to 13.7 kilobase pairs from the left end of HSV-1 EcoRI fragment D.

  13. First description of herpes simplex virus type 1 epididymo-orchitis: A new clinical form of herpes simplex virus infection during septic shock?

    PubMed

    Fromentin, Dr Mélanie; Gauzit, Remy; Gille, Benoit; Samama, Charles Marc

    2016-01-01

    Genital herpes is increasingly caused by herpes simplex virus type 1 (HSV-1), but recurrences are less frequent than with HSV-2. Distinguishing between primary genital infection and reactivation can be difficult, but HSV-1 more often causes severe primary infections and fewer recurrences. However, as virus reactivation is common during septic shock, a severe form of HSV-1 reactivation can occur in locations other than the lungs, which remain the most common site. The case of a 79-year-old Caucasian man who presented with HSV-1 epididymo-orchitis after three episodes of severe sepsis or septic shock in the context of acute biliary necrotizing pancreatitis is described. This is the first reported case of HSV-1 epididymo-orchitis due to virus reactivation during sepsis. PMID:27672563

  14. Value of the dorsal cutaneous guinea pig model in selecting topical antiviral formulations for the treatment of recurrent herpes simplex type 1 disease.

    PubMed

    Poli, G; Dall'Ara, P; Binda, S; Santus, G; Poli, A; Cocilovo, A; Ponti, W

    2001-01-01

    Recurrent herpes simplex labialis represents a disease still difficult to treat, despite the availability of many established antiviral drugs used in clinical research since 30 years ago. Although differences between the human disease and that obtained in experimental animal suggest caution in predicting an effective clinical response from the experimental results, some of the animal models seem to be useful in optimising the topical formulation of single antiviral drugs. In the present work the dorsal cutaneous guinea pig model was used to compare 5 different topical antiviral formulations with clinical promise (active molecule: 5% w/w micronized aciclovir, CAS 59277-89-3), using both roll-on and lipstick application systems. The aim being to evaluate which vehicle (water, oil, low melting and high melting fatty base) and application system (roll-on, lipstick) enhances the skin penetration and the antiviral activity of the drug, after an experimental intradermal infection with Herpes simplex virus type 1 (HSV-1). As reference, a commercial formulation (5% aciclovir ointment) was used. The cumulative results of this study showed that the formulation A, containing 5% aciclovir in an aqueous base in a roll-on application system, has the better antiviral efficacy in reducing the severity of cutaneous lesions and the viral titer; among the lipsticks preparations, the formulation D, containing 5% aciclovir in a low melting fatty base, demonstrates a very strong antiviral activity, though slightly less than formulation A. This experimental work confirms the validity of the dorsal cutaneous guinea pig model as a rapid and efficient method to compare the antiviral efficacy of new formulations, with clinical promise, to optimise the topical formulation of the active antiviral drugs. PMID:11413746

  15. Value of the dorsal cutaneous guinea pig model in selecting topical antiviral formulations for the treatment of recurrent herpes simplex type 1 disease.

    PubMed

    Poli, G; Dall'Ara, P; Binda, S; Santus, G; Poli, A; Cocilovo, A; Ponti, W

    2001-01-01

    Recurrent herpes simplex labialis represents a disease still difficult to treat, despite the availability of many established antiviral drugs used in clinical research since 30 years ago. Although differences between the human disease and that obtained in experimental animal suggest caution in predicting an effective clinical response from the experimental results, some of the animal models seem to be useful in optimising the topical formulation of single antiviral drugs. In the present work the dorsal cutaneous guinea pig model was used to compare 5 different topical antiviral formulations with clinical promise (active molecule: 5% w/w micronized aciclovir, CAS 59277-89-3), using both roll-on and lipstick application systems. The aim being to evaluate which vehicle (water, oil, low melting and high melting fatty base) and application system (roll-on, lipstick) enhances the skin penetration and the antiviral activity of the drug, after an experimental intradermal infection with Herpes simplex virus type 1 (HSV-1). As reference, a commercial formulation (5% aciclovir ointment) was used. The cumulative results of this study showed that the formulation A, containing 5% aciclovir in an aqueous base in a roll-on application system, has the better antiviral efficacy in reducing the severity of cutaneous lesions and the viral titer; among the lipsticks preparations, the formulation D, containing 5% aciclovir in a low melting fatty base, demonstrates a very strong antiviral activity, though slightly less than formulation A. This experimental work confirms the validity of the dorsal cutaneous guinea pig model as a rapid and efficient method to compare the antiviral efficacy of new formulations, with clinical promise, to optimise the topical formulation of the active antiviral drugs.

  16. [Analysis of corneal pathologic changes and laboratory parameters in herpes simplex karatitis patients with ganhuo-shangyanzheng or ganshengyinxuzheng].

    PubMed

    Zhang, H N; Li, X Q; Liang, Q H

    2001-02-28

    In order to investigate the relationship between Ganhuo shangyanzheng and Can-shengyin xuzheng in herpes simplex karatitis patients, we observed corneal pathologic changes and examined blood levels of prostaglandin F2 (PGF2), prostaglandin E2 (PGF2), tumor necrosis factor (TNF), arginine vasopressin (AVP), norepinephrine (NR), epinephrine (E) in sixty herpes simplex karatitis patients with Ganhou shangyanzheng or Gan-shengyinxuzheng. The results showed that the corneal pathologic changes were corneal ulcer infiltrating to stroma of cornea in Ganhuo shangyanzheng patients, and refractary corneal ulcer with large amount of corneal neovascularizaton and infiltration of corneal stroma in Gan-shengyinxuzheng patients, the blood levels of PGF2, PGE2, TNF, AVP, NE, E in Ganhuo shangyanzheng patients were higher than those in Gan-shengyinxuzheng patients or healthy persons. The results suggest that these parameters may be objective parameters for differential diagnosis of traditional Chinese medicine Zheng types in patients with herpes simplex karatitis.

  17. The role of a dark septate endophytic fungus, Veronaeopsis simplex Y34, in Fusarium disease suppression in Chinese cabbage.

    PubMed

    Khastini, Rida O; Ohta, Hiroyuki; Narisawa, Kazuhiko

    2012-08-01

    The soil-inhabiting fungal pathogen Fusarium oxysporum has been an increasing threat to Chinese cabbage (Brassica campestris L.). A dark septate endophytic fungus, Veronaeopsis simplex Y34, isolated from Yaku Island, Japan, was evaluated in vitro for the ability to suppress Fusarium disease. Seedlings grown in the presence of the endophyte showed a 71% reduction in Fusarium wilt disease and still had good growth. The disease control was achieved through a synergetic effect involving a mechanical resistance created by a dense network of V. simplex Y34 hyphae, which colonized the host root, and siderophore production acting indirectly to induce a resistance mechanism in the plant. Changes in the relative abundance of the fungal communities in the soil as determined by fluorescently labelled T-RFs (terminal restriction fragments), appeared 3 weeks after application of the fungus. Results showed the dominance of V. simplex Y34, which became established in the rhizosphere and out-competed F. oxysporum.

  18. Development of a reservoir type prolonged release system with felodipine via simplex methodology

    PubMed Central

    IOVANOV, RAREŞ IULIU; TOMUŢĂ, IOAN; LEUCUŢA, SORIN EMILIAN

    2016-01-01

    Background and aims Felodipine is a dihydropyridine calcium antagonist that presents good characteristics to be formulated as prolonged release preparations. The aim of the study was the formulation and in vitro characterization of a reservoir type prolonged release system with felodipine, over a 12 hours period using the Simplex method. Methods The first step of the Simplex method was to study the influence of the granules coating method on the felodipine release. Furthermore the influence of the coating polymer type, the percent of the coating polymer and the percent of pore forming agent in the coating on the felodipine release were studied. Afterwards these two steps of the experimental design the percent of Surelease applied on the felodipine loaded granules and the percent of pore former in the polymeric coating formulation variables were studied. The in vitro dissolution of model drug was performed in phosphate buffer solution (pH 6.5) with 1% sodium lauryl sulfate. The released drug quantification was done using an HPLC method. The release kinetics of felodipine from the final granules was assessed using different mathematical models. Results A 12 hours release was achieved using granules with the size between 315–500 μm coated with 45% Surelease with different pore former ratios in the coating via the top-spray method. Conclusion We have prepared prolonged release coated granules with felodipine using a fluid bed system based on the Simplex method. The API from the studied final formulations was released over a 12 hours period and the release kinetics of the model drug substance from the optimized preparations fitted best the Higuchi and Peppas kinetic models. PMID:27004036

  19. Formulation and optimization of floating matrix tablets of clarithromycin using simplex lattice design.

    PubMed

    Singh, Inderbir; Saini, Vikrant

    2016-03-01

    The purpose of the present study was to prepare floating matrix tablets of clarithromycin employing simplex lattice design. Hydroxypropyl methylcellulose (HPMC) and Ethyl Cellulose (EC) were used as matrix forming agents; sodium bicarbonate and citric acid as effervescence producing agents. Simplex lattice design was used as optimization technique employing three independent formulation variables viz. concentration of HPMC (X1), Citric Acid (X2), EC (X3) whereas floating lag time, t50%, t90%, and MDT (Mean Dissolution Time) were the response (dependent) variables. Seven formulations (F1-F7) were prepared and evaluated for dissolution studies, floating characteristics, weight variation, hardness, thickness, friability.t50% of the formulations was found to be ranging from 317±2.54 to 522±2.39 minutes. The t90% and MDT of the tablets were found to be ranging between 659.65±1.89 to 967.35±1.67 minutes and 527.20±1.22 to 846.78±2.61 minutes respectively. Total floating time of the formulations was more than 12 hours and the drug content was in the range of 98.54±0.46 to 99.92±0.32. The amount of both HPMC and EC were found to play a dominating role in controlling the release of the drug from the formulation whereas ratios of sodium bicarbonate and citric acid were showing significant effect on the floating lag time. The release exponent (n) from Korsmeyer-Peppas model was found to be between 0.62 and 0.75 indicating non-Fickian or anomalous drug release behavior from the formulated floating matrix tablets. Simplex lattice design was reported to be an effective optimization technique for optimizing pharmaceutical formulations against desired responses. PMID:27087096

  20. Histophagous ciliate Pseudocollinia brintoni and bacterial assemblage interaction with krill Nyctiphanes simplex. I. Transmission process.

    PubMed

    Gómez-Gutiérrez, Jaime; López-Cortés, Alejandro; Aguilar-Méndez, Mario J; Del Angel-Rodríguez, Jorge A; Tremblay, Nelly; Zenteno-Savín, Tania; Robinson, Carlos J

    2015-10-27

    Histophagous ciliates of the genus Pseudocollinia cause epizootic events that kill adult female krill (Euphausiacea), but their mode of transmission is unknown. We compared 16S rRNA sequences of bacterial strains isolated from stomachs of healthy krill Nyctiphanes simplex specimens with sequences of bacterial isolates and sequences of natural bacterial communities from the hemocoel of N. simplex specimens infected with P. brintoni to determine possible transmission pathways. All P. brintoni endoparasitic life stages and the transmission tomite stage (outside the host) were associated with bacterial assemblages. 16S rRNA sequences from isolated bacterial strains showed that Photobacterium spp. and Pseudoalteromonas spp. were dominant members of the bacterial assemblages during all life phases of P. brintoni and potential pathobionts. They were apparently unaffected by the krill's immune system or the histophagous activity of P. brintoni. However, other bacterial strains were found only in certain P. brintoni life phases, indicating that as the infection progressed, microhabitat conditions and microbial interactions may have become unfavorable for some strains of bacteria. Trophic infection is the most parsimonious explanation for how P. brintoni infects krill. We estimated N. simplex vulnerability to P. brintoni infection during more than three-fourths of their life span, infecting mostly adult females. The ciliates have relatively high prevalence levels (albeit at <10% of sampled stations) and a short life cycle (estimated <7 d). Histophagous ciliate-krill interactions may occur in other krill species, particularly those that form dense swarms and attain high population densities that potentially enhance trophic transmission and allow completion of the Pseudocollinia spp. life cycle. PMID:26503776

  1. Growth and nutrient removal properties of the diatoms, Chaetoceros curvisetus and C. simplex under different nitrogen sources

    NASA Astrophysics Data System (ADS)

    Karthikeyan, Panneerselvam; Manimaran, Kuppusamy; Sampathkumar, Pitchai; Rameshkumar, Lakshmanan

    2013-03-01

    To investigate the suitability of the marine diatoms, Chaetoceros curvisetus and C. simplex for the removal of macronutrients from different wastewater, the growth and nitrate-phosphate removal properties were studied with nitrate, ammonium and urea nitrogen sources. Three separate experiments were conducted using modified F/2 medium with 12.35 mg L-1 total nitrogen and 1.12 mg L-1 total phosphorous (simulating the typical concentration of nitrogen and phosphorus in secondary effluent) as growth medium. The maximum cell densities of C. curvisetus and C. simplex were 7.16 ± 0.34 × 104 cells mL-1 in {{NO}}3^{ - } and 3.88 ± 0.32 × 105 cells mL-1 in urea, respectively. The maximum chlorophyll a per cell was 1.7 and 4.7 pg for C. simplex and C. curvisetus, cultured with urea and nitrate, respectively. The high protein contents of 4.7 pg cell-1 in C. simplex with urea and 19.7 pg cell-1 in C. curvisetus nitrate nitrogen sources were found. The higher cell density and protein content of both species from urea and nitrate nitrogen sources ( p < 0.05) have shown that these were utilized by microalgae and were converted to protein. The C. simplex and C. curvisetus showed maximum removal efficiencies of nitrate by 97.86 and 91.62 % and phosphate by 98.5 and 100 %, respectively when urea used as nitrogen source than ammonia. The results indicated the C. simplex was more efficient than C. curvisetus and suitable for the removal of macronutrients when cultured with urea and nitrate nitrogen sources.

  2. Herpes simplex virus 1 counteracts viperin via its virion host shutoff protein UL41.

    PubMed

    Shen, Guanghui; Wang, Kezhen; Wang, Shuai; Cai, Mingsheng; Li, Mei-li; Zheng, Chunfu

    2014-10-01

    The interferon (IFN)-inducible viperin protein restricts a broad range of viruses. However, whether viperin plays a role during herpes simplex virus 1 (HSV-1) infection is poorly understood. In the present study, it was shown for the first time that wild-type (WT) HSV-1 infection couldn't induce viperin production, and ectopically expressed viperin inhibited the replication of UL41-null HSV-1 but not WT viruses. The underlying molecular mechanism is that UL41 counteracts viperin's antiviral activity by reducing its mRNA accumulation.

  3. Conjunctival geographic ulcer: an overlooked sign of herpes simplex virus infection.

    PubMed

    Hung, Jia-Horung; Chu, Chang-Yao; Lee, Chaw-Ning; Hsu, Chao-Kai; Lee, Julia Yu-Yun; Wang, Jen-Ren; Chang, Kung-Chao; Huang, Fu-Chin

    2015-03-01

    Herpes simplex virus (HSV) ocular infection causes significant visual burden worldwide. Despite the fact that dendritic or geographic corneal ulcers are typical findings in HSV epithelial keratitis, conjunctival ulcer as a sign of HSV infection has rarely been reported. Although easily overlooked, this important sign could be enhanced by fluorescein staining. We report two cases of conjunctival geographic ulcers proven to be HSV infection by viral isolation and polymerase chain reaction (PCR). One patient had bilateral disease and blepharitis, and the other had unilateral involvement without skin lesions. With timely diagnosis and proper management, excellent visual outcome can be expected.

  4. Cutaneous neonatal herpes simplex virus infection type 2: a case report*

    PubMed Central

    Bittencourt, Maraya de Jesus Semblano; Freitas, Lívia Karlla Marinho; Drago, Marion Guimarães; Carvalho, Alessandra Haber; do Nascimento, Bianca Angelina Macêdo

    2016-01-01

    Neonatal herpes is a serious condition. Newborns can be contaminated in utero via transplacental hematogenic transmission, upon delivery (the most frequent route), or during the postnatal period (indirect transmission). Optimal management requires prompt and accurate recognition, particularly in newborns, in order to prevent complications. Acyclovir is the treatment of choice, but its implementation is often delayed while awaiting test results, such as PCR and serology. Cytology for diagnostic purposes is rarely used in dermatology, despite the quick and reliable results. We report a case of neonatal herpes caused by type 2 herpes simplex virus diagnosed by cytology. PMID:27192523

  5. Cytotoxic T cells against herpes simplex virus in Behçet's disease.

    PubMed Central

    Hamzaoui, K; Kahan, A; Ayed, K; Hamza, M

    1990-01-01

    Lymphocytes from 36 patients with Behçet's disease (20 in remission and 16 in active phase) were stimulated in vitro with herpes simplex virus and then tested for their ability to generate cytotoxic T cell responses to the virus. Significant cytotoxic responses were found. CD4+ and CD8+ subpopulations from the patients in remission generated specific cytotoxic activity against autologous target cells. These observations suggested that CD4+ and CD8+ cytotoxic T cells may have an important host response in herpes virus infection in Behçet's disease. PMID:2168823

  6. A unique presentation of acute liver failure from herpes simplex virus hepatitis.

    PubMed

    Gutierrez, C; Kebriaei, P; Turner, K A; Yemelyanova, A; Ariza-Heredia, E J; Foo, W C

    2016-08-01

    We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortality is >80%. Early suspicion and immediate therapy are the keys to improve patient survival. PMID:27222930

  7. A simplex model of the paranoid process: implications for diagnosis and prognosis.

    PubMed

    Romney, D M

    1987-06-01

    The theory that the paranoid process is gradual and insidious was tested quantitatively by means of LISREL, a computer program designed to trace causal pathways between latent variables. The results clearly confirmed Lorr's simplex model which depicts a progressive sequence of six stages, beginning with hostile attitude and ending with delusions of influence. The model suggests that it is artificial to distinguish paranoid personality, paranoia and paranoid schizophrenia as separate diagnostic entities. Instead, paranoid schizophrenia should be regarded as a more severe form of paranoia which in turn is a more severe form of paranoid personality. The implications of this model for prognosis are also discussed.

  8. Tumour-like presentations of anogenital herpes simplex in HIV-positive patients.

    PubMed

    Ranu, H; Lee, J; Chio, M; Sen, P

    2011-04-01

    Genital and perianal ulcers seen in patients with HIV are commonly due to herpes simplex virus (HSV) infection. While it is well known that the characteristic presentation of HSV is a vesicular rash or crops of erosions, the clinical presentation of genital HSV infection in HIV is varied and can assume vegetative, hypertrophic, condyloma-like, nodular, ulcerative and tumour-like nodules or plaques. These unusual presentations often lead to a delayed diagnosis. We describe five immunocompromised HIV-positive patients with CD4 counts ranging from 114 to 326 cells/μL with unusual presentations of anogenital herpes.

  9. Survival of herpes simplex virus type 1 in saliva and tap water contaminating some common objects.

    PubMed

    Bardell, D

    1993-01-01

    Survival at room temperature (21-24 degrees C) of herpes simplex virus type 1 (HSV-1) in saliva on plastic doorknobs and chrome-plated tap handles was investigated. There was no loss of infectious virus before 30 min. Between 30 and 60 min there was a 2-log drop in titre, and infectious virus could still be recovered after 2 h, the longest period tested. The marked drop in titre coincided with drying of the saliva. There was no decline in titre of infectious HSV-1 in a humid atmosphere in which the saliva remained liquid. Similar results were seen with HSV-1 in tap water on tap handles.

  10. Herpes simplex virus type-1: replication, latency, reactivation and its antiviral targets.

    PubMed

    Pires de Mello, Camilly P; Bloom, David C; Paixão, Izabel Cnp

    2016-01-01

    Infection by herpes simplex virus type-1 (HSV-1) causes several diseases, ranging from cutaneous, oral and genital infections to fatal encephalitis. Despite the availability of antiviral therapies on the market, their efficacies are incomplete, and new cases of resistant strains arise, mainly in the immunocompromised, but also recently documented in immunocompetent patients. Over the last decades a lot has been discovered about the molecular basis of infection which has been of great benefit to the investigation of new anti-HSV-1 molecules. In this review we summarize replication, latency and reactivation highlighting potential antiviral targets and new molecules described in the past several years in the literature.

  11. Validity of the coding for herpes simplex encephalitis in the Danish National Patient Registry

    PubMed Central

    Jørgensen, Laura Krogh; Dalgaard, Lars Skov; Østergaard, Lars Jørgen; Andersen, Nanna Skaarup; Nørgaard, Mette; Mogensen, Trine Hyrup

    2016-01-01

    Background Large health care databases are a valuable source of infectious disease epidemiology if diagnoses are valid. The aim of this study was to investigate the accuracy of the recorded diagnosis coding of herpes simplex encephalitis (HSE) in the Danish National Patient Registry (DNPR). Methods The DNPR was used to identify all hospitalized patients, aged ≥15 years, with a first-time diagnosis of HSE according to the International Classification of Diseases, tenth revision (ICD-10), from 2004 to 2014. To validate the coding of HSE, we collected data from the Danish Microbiology Database, from departments of clinical microbiology, and from patient medical records. Cases were classified as confirmed, probable, or no evidence of HSE. We estimated the positive predictive value (PPV) of the HSE diagnosis coding stratified by diagnosis type, study period, and department type. Furthermore, we estimated the proportion of HSE cases coded with nonspecific ICD-10 codes of viral encephalitis and also the sensitivity of the HSE diagnosis coding. Results We were able to validate 398 (94.3%) of the 422 HSE diagnoses identified via the DNPR. Hereof, 202 (50.8%) were classified as confirmed cases and 29 (7.3%) as probable cases providing an overall PPV of 58.0% (95% confidence interval [CI]: 53.0–62.9). For “Encephalitis due to herpes simplex virus” (ICD-10 code B00.4), the PPV was 56.6% (95% CI: 51.1–62.0). Similarly, the PPV for “Meningoencephalitis due to herpes simplex virus” (ICD-10 code B00.4A) was 56.8% (95% CI: 39.5–72.9). “Herpes viral encephalitis” (ICD-10 code G05.1E) had a PPV of 75.9% (95% CI: 56.5–89.7), thereby representing the highest PPV. The estimated sensitivity was 95.5%. Conclusion The PPVs of the ICD-10 diagnosis coding for adult HSE in the DNPR were relatively low. Hence, the DNPR should be used with caution when studying patients with encephalitis caused by herpes simplex virus. PMID:27330328

  12. Effect of orifice diameter on characteristics of hollow cone swirl spray emanating from simplex nozzles

    NASA Astrophysics Data System (ADS)

    Hussein, A.; Hafiz, M.; Helmi, R.; Wisnoe, W.; Jasmi, M.

    2012-06-01

    The paper reports on experimental work to investigate the swirl spray characteristics that emanates from simplex atomizers. Main objective of the research is to investigate the effect of orifice diameter on the spray cone angle, spray breakup length and discharge coefficient at different injection pressure. Discharge coefficient is almost uninfluenced by the operating Reynolds number. This test also reveals that both breakup length and spray cone angle increases as orifice diameter is increased. Higher injection pressure leads to shorter breakup length and wider spray cone angle.

  13. Conjunctival geographic ulcer: an overlooked sign of herpes simplex virus infection.

    PubMed

    Hung, Jia-Horung; Chu, Chang-Yao; Lee, Chaw-Ning; Hsu, Chao-Kai; Lee, Julia Yu-Yun; Wang, Jen-Ren; Chang, Kung-Chao; Huang, Fu-Chin

    2015-03-01

    Herpes simplex virus (HSV) ocular infection causes significant visual burden worldwide. Despite the fact that dendritic or geographic corneal ulcers are typical findings in HSV epithelial keratitis, conjunctival ulcer as a sign of HSV infection has rarely been reported. Although easily overlooked, this important sign could be enhanced by fluorescein staining. We report two cases of conjunctival geographic ulcers proven to be HSV infection by viral isolation and polymerase chain reaction (PCR). One patient had bilateral disease and blepharitis, and the other had unilateral involvement without skin lesions. With timely diagnosis and proper management, excellent visual outcome can be expected. PMID:25728077

  14. A spectrophotometric assay for quantitative determination of kcat of herpes simplex virus type 1 thymidine kinase substrates.

    PubMed

    Schelling, P; Folkers, G; Scapozza, L

    2001-08-01

    A simple method to determine the in vitro catalytic turnover constant of several substrates of herpes simplex virus type 1 thymidine kinase is presented in this study. The method is based on a continuous spectroscopic enzyme-coupled assay and allows one to monitor the herpes simplex virus type 1 thymidine kinase activity in the presence of unlabeled substrates. A clear correlation between the catalytic turnover constant and the rate of decrease in absorbance over time during the assay has been demonstrated. Exploiting this correlation, this method has been used to determine rapidly and precisely the catalytic turnover constant of antiviral lead compounds not readily available in the radioactive labeled form.

  15. Use of Adeno-Associated and Herpes Simplex Viral Vectors for In Vivo Neuronal Expression in Mice

    PubMed Central

    Penrod, Rachel D.; Wells, Audrey M.; Carlezon, William A.; Cowan, Christopher W.

    2015-01-01

    Adeno-associated viruses and the herpes simplex virus are the two most widely used vectors for the in vivo expression of exogenous genes. Advances in the development of these vectors have enabled remarkable temporal and spatial control of gene expression. This unit provides methods for storing, delivering, and verifying expression of adeno-associated and herpes simplex viruses in the adult mouse brain. It also describes important considerations for experiments using in vivo expression of these viral vectors, including serotype and promoter selection, as well as timing of expression. Additional protocols are provided that describe methods for preliminary experiments to determine the appropriate conditions for in vivo delivery. PMID:26426386

  16. Use of Adeno-Associated and Herpes Simplex Viral Vectors for In Vivo Neuronal Expression in Mice.

    PubMed

    Penrod, Rachel D; Wells, Audrey M; Carlezon, William A; Cowan, Christopher W

    2015-01-01

    Adeno-associated viruses and the herpes simplex virus are the two most widely used vectors for the in vivo expression of exogenous genes. Advances in the development of these vectors have enabled remarkable temporal and spatial control of gene expression. This unit provides methods for storing, delivering, and verifying expression of adeno-associated and herpes simplex viruses in the adult mouse brain. It also describes important considerations for experiments using in vivo expression of these viral vectors, including serotype and promoter selection, as well as timing of expression. Additional protocols are provided that describe methods for preliminary experiments to determine the appropriate conditions for in vivo delivery.

  17. SEROLOGIC SCREENING FOR HERPES SIMPLEX VIRUS TYPE 2 IN PERSONS WITH HUMAN IMMUNODEFICIENCY VIRUS

    PubMed Central

    VAN WAGONER, NICHOLAS J; MORROW, RHODA; LEE, JEANNETTE; DIXON, PAULA; HOOK, EDWARD W.

    2013-01-01

    Screening for subclinical HSV-2 may be a useful adjunct in HIV care. However, HSV-2 serologic tests have been suggested to perform less well in HIV-infected populations. We compared HerpeSelect® HSV-2 ELISA to the Sure-Vue® Rapid HSV-2 Test for HSV-2 screening of sera from 310 HIV-infected persons receiving care at an HIV-dedicated clinic in the Southeastern United States. We determined assay agreement and whether performance of both tests, rather than 1 test alone, would improve screening accuracy. Overall percent test agreement was 96%. Negative percent agreement was best at a HerpeSelect® index value < 0.90 and positive percent agreement was best at a HerpeSelect® index value ≥ 3.0 (97% and 100%, respectively). Using the manufacturer’s established cutoffs for a HerpeSelect® positive versus negative test result discordant results between assays occurred in 4% of cases and the majority of these occurred when the HerpeSelect® index value was between 0.9 and 2.9. These data suggest good correlation between HerpeSelect® and the Sure-Vue® HSV-2 Rapid Test in a U.S. HIV-infected population and suggest that confirmatory testing may not help in HSV-2 diagnosis except in cases where HerpeSelect® index values are between 0.9–3.0. PMID:23154653

  18. Characterization of a spliced exon product of herpes simplex type-1 latency-associated transcript in productively infected cells

    SciTech Connect

    Kang, Wen; Mukerjee, Ruma; Gartner, Jared J.; Hatzigeorgiou, Artemis G.; Sandri-Goldin, Rozanne M.; Fraser, Nigel W. . E-mail: nfraser@mail.med.upenn.edu

    2006-12-20

    The latency-associated transcripts (LATs) of herpes simplex virus type-1 (HSV-1) are the only viral RNAs accumulating during latent infections in the sensory ganglia of the peripheral nervous system. The major form of LAT that accumulates in latently infected neurons is a 2 kb intron, spliced from a much less abundant 8.3 primary transcript. The spliced exon mRNA has been hard to detect. However, in this study, we have examined the spliced exon RNA in productively infected cells using ribonuclease protection (RPA), and quantitative RT-PCR (q-PCR) assays. We were able to detect the LAT exon RNA in productively infected SY5Y cells (a human neuronal cell line). The level of the LAT exon RNA was found to be approximately 5% that of the 2 kb intron RNA and thus is likely to be relatively unstable. Quantitative RT-PCR (q-PCR) assays were used to examine the LAT exon RNA and its properties. They confirmed that the LAT exon mRNA is present at a very low level in productively infected cells, compared to the levels of other viral transcripts. Furthermore, experiments showed that the LAT exon mRNA is expressed as a true late gene, and appears to be polyadenylated. In SY5Y cells, in contrast to most late viral transcripts, the LAT exon RNA was found to be mainly nuclear localized during the late stage of a productive infection. Interestingly, more LAT exon RNA was found in the cytoplasm in differentiated compared to undifferentiated SY5Y cells, suggesting the nucleocytoplasmic distribution of the LAT exon RNA and its related function may be influenced by the differentiation state of cells.

  19. Inactivation of acyclovir-sensitive and -resistant strains of herpes simplex virus type 1 in vitro by photodynamic antimicrobial chemotherapy

    PubMed Central

    Latief, Miftahul Akhyar; Ko, Ji-Ae; Kiuchi, Yoshiaki; Sakaguchi, Takemasa; Obana, Akira

    2015-01-01

    Purpose To evaluate the efficacy of photodynamic antimicrobial chemotherapy (PACT) with the new porphyrin derivative TONS 504 and a light-emitting diode (LED) against acyclovir (ACV)-sensitive and -resistant herpes simplex virus type 1 (HSV-1). Methods Human FL cells infected with the viral strains were subjected to PACT with TONS 504 at various concentrations (0.01 to 10 mg/l) and irradiation at various light energies (10 to 30 J/cm2) and were then incubated for 24 h before analysis. Results Immunocytofluorescence analysis with antibodies to HSV-1 revealed that PACT eliminated HSV-1 and ACV-resistant HSV-1 in a manner dependent on the TONS 504 concentration and light energy. Complete eradication of both viruses was apparent at a TONS 504 concentration of 10 mg/l and light energy of 10 to 30 J/cm2 as well as at a TONS 504 concentration of 1 mg/l and light energy of 20 or 30 J/cm2. No antiviral effect was apparent with TONS 504 in the absence of irradiation or with irradiation in the absence of TONS 504. Staining of cell nuclei with 4′, 6-diamidino-2-phenylindole revealed no apparent cytotoxicity of the PACT system, a finding that was confirmed by the system’s failure to induce the release of lactate dehydrogenase from the host cells. Conclusions We conclude that our PACT system based on TONS 504 and an LED is effective for eliminating HSV-1 and ACV-resistant HSV-1 without a harmful effect on host cells. PMID:25999680

  20. Protection against herpes simplex virus infection in mice by recombinant murine interferon-beta in combination with antibody.

    PubMed

    Kumano, Y; Yamamoto, M; Mori, R

    1987-06-01

    A recombinant murine interferon -beta (rMuIFN-beta) was used to suppress the development of skin lesions and death of mice after challenge with herpes simplex virus (HSV) type 1 (HSV-1). Depilated female BALB/c mice were inoculated intradermally with HSV-1, Hayashida strain, and were administered various concentrations of interferon (IFN) intraperitoneally 3 h later. The treatment with IFN was given once a day for 10 successive days. Under the conditions in which almost all control mice died after development of severe zosteriform skin lesions, the mortality of mice treated with IFN (8 X 10(5) or 8 X 10(4) U/mouse) was less than 50% (9/20 and 4/10, respectively), though all mice treated with a lower dose of IFN (8 X 10(3) U/mouse) died. Titration revealed that there was no significant suppression of virus growth by IFN in the skin or dorsal root ganglia, but it was significantly suppressed in the brain. The protective effect of IFN was enhanced when it was used in combination with human anti-HSV antibody having a neutralizing titer (NT) of 1:16. All mice treated with IFN (8 X 10(5) U/mouse) and antibody (NT, 1:16) survived, and only 40% of them developed slight zosteriform skin lesions. The effect of the combination was observed even when both IFN and antibody were diluted 1:10. The protective effect of IFN was also observed when athymic nude mice were used as the host. In this system, though the IFN-treated nude mice survived significantly longer than the controls, they finally died. In antibody- or acyclovir (ACV)-treated nude mice, there was also a prolongation of survival time as compared with control mice. The effect of antibody was enhanced by the addition of IFN, but IFN did not potentiate the effect of ACV.

  1. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity.

    PubMed

    Guo, Yiqi; Audry, Magali; Ciancanelli, Michael; Alsina, Laia; Azevedo, Joana; Herman, Melina; Anguiano, Esperanza; Sancho-Shimizu, Vanessa; Lorenzo, Lazaro; Pauwels, Elodie; Philippe, Paul Bastard; Pérez de Diego, Rebeca; Cardon, Annabelle; Vogt, Guillaume; Picard, Capucine; Andrianirina, Zafitsara Zo; Rozenberg, Flore; Lebon, Pierre; Plancoulaine, Sabine; Tardieu, Marc; Valérie Doireau; Jouanguy, Emmanuelle; Chaussabel, Damien; Geissmann, Frederic; Abel, Laurent; Casanova, Jean-Laurent; Zhang, Shen-Ying

    2011-09-26

    Autosomal dominant TLR3 deficiency has been identified as a genetic etiology of childhood herpes simplex virus 1 (HSV-1) encephalitis (HSE). This defect is partial, as it results in impaired, but not abolished induction of IFN-β and -λ in fibroblasts in response to TLR3 stimulation. The apparently normal resistance of these patients to other infections, viral illnesses in particular, may thus result from residual TLR3 responses. We report here an autosomal recessive form of complete TLR3 deficiency in a young man who developed HSE in childhood but remained normally resistant to other infections. This patient is compound heterozygous for two loss-of-function TLR3 alleles, resulting in an absence of response to TLR3 activation by polyinosinic-polycytidylic acid (poly(I:C)) and related agonists in his fibroblasts. Moreover, upon infection of the patient's fibroblasts with HSV-1, the impairment of IFN-β and -λ production resulted in high levels of viral replication and cell death. In contrast, the patient's peripheral blood mononuclear cells responded normally to poly(I:C) and to all viruses tested, including HSV-1. Consistently, various TLR3-deficient leukocytes from the patient, including CD14(+) and/or CD16(+) monocytes, plasmacytoid dendritic cells, and in vitro derived monocyte-derived macrophages, responded normally to both poly(I:C) and HSV-1, with the induction of antiviral IFN production. These findings identify a new genetic etiology for childhood HSE, indicating that TLR3-mediated immunity is essential for protective immunity to HSV-1 in the central nervous system (CNS) during primary infection in childhood, in at least some patients. They also indicate that human TLR3 is largely redundant for responses to double-stranded RNA and HSV-1 in various leukocytes, probably accounting for the redundancy of TLR3 for host defense against viruses, including HSV-1, outside the CNS. PMID:21911422

  2. Prophylactic, therapeutic and neutralizing effects of zinc oxide tetrapod structures against herpes simplex virus type-2 infection

    PubMed Central

    Antoine, Thessicar; Mishra, Yogendra K.; Trigilio, James; Tiwari, Vaibhav; Adelung, Rainer; Shukla, Deepak

    2012-01-01

    The attachment of Herpes simplex virus type-2 (HSV-2) to a target cell requires ionic interactions between negatively charged cell surface co-receptor heparan sulfate (HS) and positively charged residues on viral envelop glycoproteins, gB and gC. Effective blocking of this first step of HSV-2 pathogenesis demonstrates significant prophylactic effects against the viral disease; any in vitro therapeutic effects of blocking this interaction, however, are not clear. Here, we provide new evidence that zinc oxide tetrapod micro-nanostructures synthesized by flame transport approach significantly block HSV-2 entry into target cells and, in addition, demonstrate the potential to stop the spread of the virus among already infected cells. The zinc oxide tetrapods (ZnOTs) also exhibit the ability to neutralize HSV-2 virions. Natural target cells such as human vaginal epithelial and HeLa cells showed highly reduced infectivity when infected with HSV-2 virions that were pre-incubated with the ZnOTs. The mechanism behind the ability of ZnOTs to prevent, neutralize or reduce HSV-2 infection relies on their ability to bind the HSV-2 virions. We used fluorescently labeled ZnOTs and GFP-expressing HSV-2 virions to demonstrate the binding of the ZnOTs with HSV-2. We also show that the binding and hence, the anti-viral effects of ZnOTs can be enhanced by illuminating the ZnOTs with UV light. Our results provide new insights into the anti-HSV-2 effects of ZnOT and rationalize their development as a HSV-2 trapping agent for the prevention and/or treatment of infection. The observed results also demonstrate that blocking HSV-2 attachment can have prophylactic as well as therapeutic applications. PMID:23047013

  3. Combination effect of oncolytic adenovirus therapy and herpes simplex virus thymidine kinase/ganciclovir in hepatic carcinoma animal models

    PubMed Central

    Zheng, Fei-qun; Xu, Yin; Yang, Ren-jie; Wu, Bin; Tan, Xiao-hua; Qin, Yi-de; Zhang, Qun-wei

    2009-01-01

    Aim: Oncolytic adenovirus, also called conditionally replicating adenovirus (CRAD), can selectively propagate in tumor cells and cause cell lysis. The released viral progeny can infect neighboring cancer cells, initiating a cascade that can lead to the ultimate destruction of the tumor. Suicide gene therapy using herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) offers a potential treatment strategy for cancer and is undergoing preclinical trials for a variety of tumors. We hypothesized that HSV-TK gene therapy combined with oncolytic adenoviral therapy would have an enhanced effect compared with the individual effects of the therapies and is a potential novel therapeutic strategy to treat liver cancer. Methods: To address our hypothesis, a novel CRAD was created, which consisted of a telomerase-dependent oncolytic adenovirus engineered to express E1A and HSV-TK genes (Ad-ETK). The combined effect of Ad-ETK and GCV was assessed both in vitro and in vivo in nude mice bearing HepG2 cell-derived tumors. Expression of the therapeutic genes by the transduced tumor cells was analyzed by RT-PCR and Western blotting. Results: We confirmed that Ad-ETK had antitumorigenic effects on human hepatocellular carcinoma (HCC) both in vitro and in vivo, and the TK/GCV system enhanced oncolytic adenoviral therapy. We confirmed that both E1A and HSV-TK genes were expressed in vivo. Conclusion: The Ad-ETK construct should provide a relatively safe and selective approach to killing cancer cells and should be investigated as an adjuvant therapy for hepatocellular carcinoma. PMID:19363518

  4. Genotypic Characterization of Herpes Simplex Virus Type 1 Isolates in Immunocompromised Patients in Rio de Janeiro, Brazil

    PubMed Central

    Perse da Silva, Amanda; Lopes, Amanda de Oliveira; Vieira, Yasmine Rangel; de Almeida, Adilson José; Sion, Fernando Samuel; Grinsztejn, Beatriz; Wagner, Sandra; de Paula, Vanessa Salete

    2015-01-01

    Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen that causes a variety of diseases, including an increased risk of developing more severe disease in HIV-infected individuals. In Brazil, there is no information about the molecular epidemiology of HSV-1 infection, especially in HIV-infected individuals. The aim of this study was to perform the genotypic characterization of HSV-1 among HIV-infected patients. A total of 214 serum samples from HIV-positive patients without HSV infection symptoms were enrolled in one of two reference hospitals for HIV infection managing in Rio de Janeiro. The gG and gI genes were analyzed by restriction fragment length polymorphism (RFLP) and full nucleotide sequencing of the US8 (1601 bp), UL44 (1996 bp), and UL23 (1244 bp) regions was performed. A total of 38.3% (82/214) and 32.7% (70/214) of the serum samples tested positive for gG and gI genes, respectively. RFLP analysis classified the HSV-1 as belonging to genotype A. Phylogenetic analysis of the Brazilian samples for the US8, UL44, and UL23 regions demonstrated that the nucleotide identity between Brazilian samples was higher than 97% for all genes. No acyclovir mutation was detected in the patients. The shedding of HSV in the serum samples from HIV-positive patients who were asymptomatic for HSV infection was detected in this work. This is the first report of molecular characterization of HSV-1 in Brazilian samples since there is no previous data available in the literature concerning the genotypic classification and stable distribution of Brazilian strains of HSV-1 in Rio de Janeiro, Brazil. PMID:26407292

  5. Prophylactic, therapeutic and neutralizing effects of zinc oxide tetrapod structures against herpes simplex virus type-2 infection.

    PubMed

    Antoine, Thessicar E; Mishra, Yogendra K; Trigilio, James; Tiwari, Vaibhav; Adelung, Rainer; Shukla, Deepak

    2012-12-01

    The attachment of Herpes simplex virus type-2 (HSV-2) to a target cell requires ionic interactions between negatively charged cell surface co-receptor heparan sulfate (HS) and positively charged residues on viral envelop glycoproteins, gB and gC. Effective blocking of this first step of HSV-2 pathogenesis demonstrates significant prophylactic effects against the viral disease; any in vitro therapeutic effects of blocking this interaction, however, are not clear. Here, we provide new evidence that zinc oxide tetrapod micro-nanostructures synthesized by flame transport approach significantly block HSV-2 entry into target cells and, in addition, demonstrate the potential to stop the spread of the virus among already infected cells. The zinc oxide tetrapods (ZnOTs) also exhibit the ability to neutralize HSV-2 virions. Natural target cells such as human vaginal epithelial and HeLa cells showed highly reduced infectivity when infected with HSV-2 virions that were pre-incubated with the ZnOTs. The mechanism behind the ability of ZnOTs to prevent, neutralize or reduce HSV-2 infection relies on their ability to bind the HSV-2 virions. We used fluorescently labeled ZnOTs and GFP-expressing HSV-2 virions to demonstrate the binding of the ZnOTs with HSV-2. We also show that the binding and hence, the antiviral effects of ZnOTs can be enhanced by illuminating the ZnOTs with UV light. Our results provide new insights into the anti-HSV-2 effects of ZnOT and rationalize their development as a HSV-2 trapping agent for the prevention and/or treatment of infection. The observed results also demonstrate that blocking HSV-2 attachment can have prophylactic as well as therapeutic applications. PMID:23047013

  6. Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action.

    PubMed

    Ceña-Diez, Rafael; Vacas-Córdoba, Enrique; García-Broncano, Pilar; de la Mata, F J; Gómez, Rafael; Maly, Marek; Muñoz-Fernández, M Ángeles

    2016-01-01

    Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3-S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3-S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH-gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2-S16, providing a step forward to prevent HSV-2 transmission in humans.

  7. Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

    PubMed Central

    Ceña-Diez, Rafael; Vacas-Córdoba, Enrique; García-Broncano, Pilar; de la Mata, FJ; Gómez, Rafael; Maly, Marek; Muñoz-Fernández, Mª Ángeles

    2016-01-01

    Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3-S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3-S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH–gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2-S16, providing a step forward to prevent HSV-2 transmission in humans. PMID:27274240

  8. Synthetic α-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses

    PubMed Central

    Ireland, Peter J.; Tavis, John E.; D'Erasmo, Michael P.; Hirsch, Danielle R.; Murelli, Ryan P.; Cadiz, Mark M.; Patel, Bindi S.; Gupta, Ankit K.; Edwards, Tiffany C.; Korom, Maria; Moran, Eileen A.

    2016-01-01

    Herpes simplex virus 1 (HSV-1) and HSV-2 remain major human pathogens despite the development of anti-HSV therapeutics as some of the first antiviral drugs. Current therapies are incompletely effective and frequently drive the evolution of drug-resistant mutants. We recently determined that certain natural troponoid compounds such as β-thujaplicinol readily suppress HSV-1 and HSV-2 replication. Here, we screened 26 synthetic α-hydroxytropolones with the goals of determining a preliminary structure-activity relationship for the α-hydroxytropolone pharmacophore and providing a starting point for future optimization studies. Twenty-five compounds inhibited HSV-1 and HSV-2 replication at 50 μM, and 10 compounds inhibited HSV-1 and HSV-2 at 5 μM, with similar inhibition patterns and potencies against both viruses being observed. The two most powerful inhibitors shared a common biphenyl side chain, were capable of inhibiting HSV-1 and HSV-2 with a 50% effective concentration (EC50) of 81 to 210 nM, and also strongly inhibited acyclovir-resistant mutants. Moderate to low cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC50] of 50 to >100 μM). Therapeutic indexes ranged from >170 to >1,200. These data indicate that troponoids and specifically α-hydroxytropolones are a promising lead scaffold for development as anti-HSV drugs provided that toxicity can be further minimized. Troponoid drugs are envisioned to be employed alone or in combination with existing nucleos(t)ide analogs to suppress HSV replication far enough to prevent viral shedding and to limit the development of or treat nucleos(t)ide analog-resistant mutants. PMID:26787704

  9. Amino acid substitutions in the thymidine kinase gene of induced acyclovir-resistant herpes simplex virus type 1

    NASA Astrophysics Data System (ADS)

    Hussin, Ainulkhir; Nor, Norefrina Shafinaz Md; Ibrahim, Nazlina

    2013-11-01

    Acyclovir (ACV) is an antiviral drug of choice in healthcare setting to treat infections caused by herpes viruses, including, but not limited to genital herpes, cold sores, shingles and chicken pox. Acyclovir resistance has emerged significantly due to extensive use and misuse of this antiviral in human, especially in immunocompromised patients. However, it remains unclear about the amino acid substitutions in thymidine (TK) gene, which specifically confer the resistance-associated mutation in herpes simplex virus. Hence, acyclovir-resistant HSV-1 was selected at high concentration (2.0 - 4.5 μg/mL), and the TK-gene was subjected to sequencing and genotypic characterization. Genotypic sequences comparison was done using HSV-1 17 (GenBank Accesion no. X14112) for resistance-associated mutation determination whereas HSV-1 KOS, HSV-1 473/08 and HSV clinical isolates sequences were used for polymorphism-associated mutation. The result showed that amino acid substitutions at the non-conserved region (UKM-1: Gln34Lys, UKM-2: Arg32Ser & UKM-5: Arg32Cys) and ATP-binding site (UKM-3: Tyr53End & UKM-4: Ile54Leu) of the TK-gene. These discoveries play an important role to extend another dimension to the evolution of acyclovir-resistant HSV-1 and suggest that selection at high ACV concentration induced ACV-resistant HSV-1 evolution. These findings also expand the knowledge on the type of mutations among acyclovir-resistant HSV-1. In conclusion, HSV-1 showed multiple strategies to exhibit acyclovir resistance, including amino acid substitutions in the TK gene.

  10. Latent Herpes Simplex Virus Infections in Sensory Ganglia of Hairless Mice Prevented by Acycloguanosine†

    PubMed Central

    Klein, Richard J.; Friedman-Kien, Alvin E.; DeStefano, Eugene

    1979-01-01

    Acycloguanosine (ACG) was able to prevent the fatal outcome of herpes simplex virus-induced skin infections of the lumbosacral or orofacila area in hairless mice. Topical ACG treatment was more effective than systemic treatment in preventing the evolution of skin lesions. Acute ganglionic infections in the trigeminal ganglia were prevented by ACG, and latent ganglionic infections did not become established when the ACG treatment was initiated 3 h after infection. Serum antibody titers were, on the average, eight times higher in mice which developed latent ganglionic infections after ACG treatment than in mice without evidence of herpes simplex virus latency in ganglia. Reinoculation of ACG-treated mice at a site different from that of the primary inoculation did not lead to the establishment of a second latent infection with the homologous virus type when a latent infection was already present. In mice without evidence of latent infection after the primary inoculation, a latent infection at the site of reinoculation became established in 25% of the animals. PMID:230784

  11. Larval trematodes Paronatrema mantae and Copiatestes sp. parasitize Gulf of California krill (Nyctiphanes simplex, Nematoscelis difficilis).

    PubMed

    Morales-Ávila, José Raúl; Gómez-Gutiérrez, Jaime; del Carmen Gómez del Prado-Rosas, María; Robinson, Carlos J

    2015-09-17

    During 4 quantitative-systematic oceanographic cruises at 99 sampling stations in the Gulf of California (January and July 2007, August 2012, and June 2013), we found 2 trematode species (non-encysted mesocercaria stage) parasitizing the hemocoel of 2 krill species at near-shore locations. Copiatestes sp. parasitized Nematoscelis difficilis in January 2007, and Paronatrema mantae parasitized Nyctiphanes simplex in July 2007. Both trematode species had an intensity of 1 parasite per host. This is the first endoparasite known for N. difficilis, the first record of P. mantae infecting zooplankton, and the first confirmed trematode parasitizing krill species in the Gulf of California. We provide quantitative evidence that these 2 trematode species infect krill with considerably low station prevalence (0.03-0.16%) and low population abundances (<1.2 trematodes 1000 m(-3)). A review of trematodes parasitizing krill indicates that syncoeliid trematodes also have (with few exceptions) low population densities and prevalence and lower species diversity than previously thought (suggesting a broader zoogeographic distribution range of these parasites). Due to the low host specificity of syncoeliid trematodes that typically infect more than 1 secondary intermediate host species in their complex life cycle, we propose that N. simplex and N. difficilis are intermediate hosts (although non-conspicuous) for the transmission of syncoeliid trematodes in the Gulf of California. PMID:26378405

  12. Simplex and duplex event-specific analytical methods for functional biotech maize.

    PubMed

    Lee, Seong-Hun; Kim, Su-Jeong; Yi, Bu-Young

    2009-08-26

    Analytical methods are very important in the control of genetically modified organism (GMO) labeling systems or living modified organism (LMO) management for biotech crops. Event-specific primers and probes were developed for qualitative and quantitative analysis for biotech maize event 3272 and LY 038 on the basis of the 3' flanking regions, respectively. The qualitative primers confirmed the specificity by a single PCR product and sensitivity to 0.05% as a limit of detection (LOD). Simplex and duplex quantitative methods were also developed using TaqMan real-time PCR. One synthetic plasmid was constructed from two taxon-specific DNA sequences of maize and two event-specific 3' flanking DNA sequences of event 3272 and LY 038 as reference molecules. In-house validation of the quantitative methods was performed using six levels of mixing samples, from 0.1 to 10.0%. As a result, the biases from the true value and the relative deviations were all within the range of +/-30%. Limits of quantitation (LOQs) of the quantitative methods were all 0.1% for simplex real-time PCRs of event 3272 and LY 038 and 0.5% for duplex real-time PCR of LY 038. This study reports that event-specific analytical methods were applicable for qualitative and quantitative analysis for biotech maize event 3272 and LY 038. PMID:19650633

  13. Recombination in vitro between herpes simplex virus type 1 a sequences.

    PubMed Central

    Bruckner, R C; Dutch, R E; Zemelman, B V; Mocarski, E S; Lehman, I R

    1992-01-01

    We have partially purified an activity from extracts of cells infected with herpes simplex virus type 1 that mediates recombination between repeated copies of the 317-base-pair a sequence of herpes simplex virus type 1. Recombination leads to deletion of a lacZ indicator gene situated between two directly repeated copies of the a sequence and is scored by transformation of lacZ- Escherichia coli. The two products of the reaction can be observed directly by restriction enzyme digestion and Southern blot analysis. The recombinase activity is also detectable, but at a lower level, in uninfected cell extracts. The DNA substrate must contain the two a sequences arranged in direct orientation to generate the lacZ deletion. However, when the a sequences are arranged in inverted orientation, an inversion results. A substrate with two homologous sequences of size and G + C content similar to the a sequence undergoes recombination at a much lower frequency. The reaction requires a divalent cation (Mg2+ or Mn2+) but not ATP or any other nucleoside triphosphate. The simple requirements and specificity for the a sequence suggest that the recombination may proceed by a site-specific mechanism. Images PMID:1332062

  14. Attachment and penetration of acyclovir-resistant herpes simplex virus are inhibited by Melissa officinalis extract.

    PubMed

    Astani, Akram; Navid, Mojdeh Heidary; Schnitzler, Paul

    2014-10-01

    Medicinal plants are increasingly of interest as novel source of drugs for antiherpetic agents, because herpes simplex virus (HSV) might develop resistance to commonly used antiviral drugs. An aqueous extract of Melissa officinalis and the phenolic compounds caffeic acid, p-coumaric acid and rosmarinic acid were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) acyclovir-sensitive and clinical isolates of acyclovir-resistant strains in vitro. When drugs were added during the intracellular replication of HSV-1 infected cells, no antiviral effect was observed by plaque reduction assay. However, Melissa extract interacted directly with free viral particles of two acyclovir-resistant HSV strains at low IC50 values of 0.13 and 0.23 µg/mL and high selectivity indices of 2692 and 1522, respectively. The Melissa extract and rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent manner for acyclovir-sensitive and acyclovir-resistant strains. These results indicate that mainly rosmarinic acid contributed to the antiviral activity of Melissa extract. Penetration of herpes viruses into cells was inhibited by Melissa extract at 80% and 96% for drug-sensitive and drug-resistant viruses, respectively. Melissa extract exhibits low toxicity and affects attachment and penetration of acyclovir-sensitive and acyclovir-resistant HSVs in vitro.

  15. An accurate skull stripping method based on simplex meshes and histogram analysis for magnetic resonance images.

    PubMed

    Galdames, Francisco J; Jaillet, Fabrice; Perez, Claudio A

    2012-01-01

    Skull stripping methods are designed to eliminate the non-brain tissue in magnetic resonance (MR) brain images. Removal of non-brain tissues is a fundamental step in enabling the processing of brain MR images. The aim of this study is to develop an automatic accurate skull stripping method based on deformable models and histogram analysis. A rough-segmentation step is used to find the optimal starting point for the deformation and is based on thresholds and morphological operators. Thresholds are computed using comparisons with an atlas, and modeling by Gaussians. The deformable model is based on a simplex mesh and its deformation is controlled by the image local gray levels and the information obtained on the gray level modeling of the rough-segmentation. Our Simplex Mesh and Histogram Analysis Skull Stripping (SMHASS) method was tested on the following international databases commonly used in scientific articles: BrainWeb, Internet Brain Segmentation Repository (IBSR), and Segmentation Validation Engine (SVE). A comparison was performed against three of the best skull stripping methods previously published: Brain Extraction Tool (BET), Brain Surface Extractor (BSE), and Hybrid Watershed Algorithm (HWA). Performance was measured using the Jaccard index (J) and Dice coefficient (κ). Our method showed the best performance and differences were statistically significant (p<0.05): J=0.904 and κ=0.950 on BrainWeb; J=0.905 and κ=0.950 on IBSR; J=0.946 and κ=0.972 on SVE.

  16. Surveying the endomicrobiome and ectomicrobiome of bark beetles: The case of Dendroctonus simplex.

    PubMed

    Durand, Audrey-Anne; Bergeron, Amélie; Constant, Philippe; Buffet, Jean-Philippe; Déziel, Eric; Guertin, Claude

    2015-11-26

    Many bark beetles belonging to the Dendroctonus genus carry bacterial and fungal microbiota, forming a symbiotic complex that helps the insect to colonize the subcortical environment of the host tree. However, the biodiversity of those bacteria at the surface of the cuticle or inside the body parts of bark beetles is not well established. The aim of this study was to characterize the bacterial microbiome associated with the eastern larch beetle, Dendroctonus simplex, using bacterial 16S rRNA gene pyrosequencing. The ecto- and endomicrobiome and the subcortical galleries were investigated. Several bacterial genera were identified, among which Pseudomonas, Serratia and Yersinia are associated with the surface of the beetle cuticle, and genera belonging to Enterobacteriaceae and Gammaproteobacteria with the interior of the insect body. The index of dissimilarity indicates that the bacterial microbiome associated with each environment constitutes exclusive groups. These results suggest the presence of distinct bacterial microbiota on the surface of the cuticle and the interior of D. simplex body. Additionally, the bacterial diversity identified in the galleries is substantially different from the ectomicrobiome, which could indicate a selection by the insect. This study reports for the first time the identification of the eastern larch beetle microbiome.

  17. Surveying the endomicrobiome and ectomicrobiome of bark beetles: The case of Dendroctonus simplex

    PubMed Central

    Durand, Audrey-Anne; Bergeron, Amélie; Constant, Philippe; Buffet, Jean-Philippe; Déziel, Eric; Guertin, Claude

    2015-01-01

    Many bark beetles belonging to the Dendroctonus genus carry bacterial and fungal microbiota, forming a symbiotic complex that helps the insect to colonize the subcortical environment of the host tree. However, the biodiversity of those bacteria at the surface of the cuticle or inside the body parts of bark beetles is not well established. The aim of this study was to characterize the bacterial microbiome associated with the eastern larch beetle, Dendroctonus simplex, using bacterial 16S rRNA gene pyrosequencing. The ecto- and endomicrobiome and the subcortical galleries were investigated. Several bacterial genera were identified, among which Pseudomonas, Serratia and Yersinia are associated with the surface of the beetle cuticle, and genera belonging to Enterobacteriaceae and Gammaproteobacteria with the interior of the insect body. The index of dissimilarity indicates that the bacterial microbiome associated with each environment constitutes exclusive groups. These results suggest the presence of distinct bacterial microbiota on the surface of the cuticle and the interior of D. simplex body. Additionally, the bacterial diversity identified in the galleries is substantially different from the ectomicrobiome, which could indicate a selection by the insect. This study reports for the first time the identification of the eastern larch beetle microbiome. PMID:26608752

  18. Virus-specific antibodies in sera from patients with genital herpes simplex virus infection.

    PubMed Central

    Zweerink, H J; Corey, L

    1982-01-01

    Virus-specific antibodies against a number of herpes simplex virus type 2 antigens were determined by radioimmunoprecipitation assays in sequential serum samples obtained from 12 patients with initial genital herpes simplex virus infection. The progressive appearance of antibodies to virus-specific antigens was observed; antibodies against a 130,000-molecular-weight glycoprotein complex appeared first, followed by antibodies against the major nucleocapsid polypeptide and then antibodies against a number of other viral antigens, including a polypeptide with a molecular weight of 62,000. Patients who developed a wide variety of antibodies to viral polypeptides shortly after resolution of their initial episode seemed to experience more severe initial infections and more recurrences than did those who reacted poorly with these virus-specific antigens. This was most apparent with respect to antibodies to virus-specific polypeptides with molecular weights between 30,000 and 43,000. Antibody specificity did not change during the course of follow-up regardless of whether serum samples were taken shortly before, during, or after recurrent episodes. Glycoprotein-specific antibodies were quantitated with the purified 130,000-molecular-weight glycoprotein material. No significant fluctuations in these antibody titers were observed before or after recurrences of the disease. Images PMID:7118244

  19. Phenotypic switching in cells transformed with the herpes simplex virus thymidine kinase gene

    SciTech Connect

    Ostrander, M.; Vogel, S.; Silverstein, S.

    1982-06-01

    Biochemical transformation of Ltk/sup -/ cells with the herpes simplex virus thymidine kinase (tk) gene resulted in numerous TK/sup +/ colonies that survived selection in hypoxanthine-aminopterin-thymidine medium. Many of these TK/sup +/ cell lines switched phenotypes and reverted to the TK/sup -/ state. In this report, the authors describe the biological and biochemical characteristics of three TK/sup -/ revertant lines. One (K/sub 1/B/sub 5/) transiently expressed TK in the presence of bromodeoxyuridine, which selects for the TK/sup -/ phenotype. Another TK/sup -/ sibling (K/sub 1/B/sub 6//sup n/) expressed TK only after removal from bromodeoxyuridine-containing medium. The last variant (K/sub 1/B/sub 6//sup me/) lost the ability to switch to the TK/sup +/ phenotype, although it maintained the herpes simplex virus sequences coding for TK. Loss of the ability of K/sub 1/B/sub 6//sup me/ cells to express TK was correlated with extensive methylation of the sequence recognized by the restriction endonuclease HpaII (pCpCpGpG). After these cells were treated with 5-azacytidine, they regained the ability to clone in hypoxanthine-aminopterin-thymidine medium and reexpressed virus tk mRNA and enzyme. In addition, the HpaII sites that were previously shown to be refractile to enzyme digestion were converted to a sensitive state, demonstrating that they were no longer methylated.

  20. Forces and Structures of the Herpes Simplex Virus (HSV) Entry Mechanism.

    PubMed

    Clarke, Richard W

    2015-09-11

    This paper discusses physical and structural aspects of the mechanisms herpes simplex virus (HSV) uses for membrane fusion. Calculations show that herpes simplex virus glycoprotein D has such avidity for its receptors that it can hold the virion against the plasma membrane of a neuron strongly enough for glycoprotein B (gB) to disrupt both leaflets of the bilayer. The strong electric field generated by the cell potential across perforations at this disruption would break the hydrogen bonds securing the gB fusion loops, leading to fusion of the plasma and viral membranes. This mechanism agrees with the high stability of the tall trimeric spike structure of gB and is consistent with the probable existence of a more compact initial conformation that would allow it to closely approach the plasma membrane. The release of the fusion domains by disruption of hydrogen bonds is shared with the endocytotic entry pathway where, for some cell types not punctured by gB, the virus is able to induce inward forces that cause endocytosis and the fusion loops are released by acidification. The puncture-fusion mechanism requires low critical strain or high tissue strain, matching primary tropism of neural processes at the vermillion border. In support of this mechanism, this paper proposes a functional superstructure of the antigens essential to entry and reviews its consistency with experimental evidence. PMID:27617923

  1. Concurrent herpes simplex type 1 necrotizing encephalitis, cytomegalovirus ventriculoencephalitis and cerebral lymphoma in an AIDS patient.

    PubMed

    Vital, C; Monlun, E; Vital, A; Martin-Negrier, M L; Cales, V; Leger, F; Longy-Boursier, M; Le Bras, M; Bloch, B

    1995-01-01

    Unlike cytomegalovirus (CMV) ventriculoencephalitis, herpes simplex virus type 1 necrotizing encephalitis has only rarely been observed in AIDS patients. A 40-year-old bisexual man was followed for an HIV1 infection from 1987 onwards. In June 1993 he was referred for sudden confusion, left hemiparesia and fever. The blood contained less than 10 CD4 lymphocytes/mm3. The patient remained comatose and febrile, and died 4 weeks later. In coronal sections of the brain there was necrosis of the internal parts of the left temporal lobe, necrosis of certain areas of the ventricular walls and a small tumor at the top of the right frontal lobe, which proved to be a polymorphic high-grade lymphoma. CMV ventriculoencephalitis lesions were prominent in the ventricular walls of the occipital lobes and there was a strong nuclear signal for CMV using in situ hybridization. Herpes simplex virus type 1 was shown in the nuclei and cytoplasm of certain neurons and astrocytes in the borders of the necrotized temporal lobe areas by immunohistochemistry, in situ hybridization and electron microscopy, whereas in situ hybridization and immunohistochemistry for CMV were negative in such areas. Necrotizing type 1 encephalitis must not be overlooked in immunodeficient patients. PMID:7709722

  2. Simplex and duplex event-specific analytical methods for functional biotech maize.

    PubMed

    Lee, Seong-Hun; Kim, Su-Jeong; Yi, Bu-Young

    2009-08-26

    Analytical methods are very important in the control of genetically modified organism (GMO) labeling systems or living modified organism (LMO) management for biotech crops. Event-specific primers and probes were developed for qualitative and quantitative analysis for biotech maize event 3272 and LY 038 on the basis of the 3' flanking regions, respectively. The qualitative primers confirmed the specificity by a single PCR product and sensitivity to 0.05% as a limit of detection (LOD). Simplex and duplex quantitative methods were also developed using TaqMan real-time PCR. One synthetic plasmid was constructed from two taxon-specific DNA sequences of maize and two event-specific 3' flanking DNA sequences of event 3272 and LY 038 as reference molecules. In-house validation of the quantitative methods was performed using six levels of mixing samples, from 0.1 to 10.0%. As a result, the biases from the true value and the relative deviations were all within the range of +/-30%. Limits of quantitation (LOQs) of the quantitative methods were all 0.1% for simplex real-time PCRs of event 3272 and LY 038 and 0.5% for duplex real-time PCR of LY 038. This study reports that event-specific analytical methods were applicable for qualitative and quantitative analysis for biotech maize event 3272 and LY 038.

  3. Specific Inhibition of Herpes Simplex Virus DNA Polymerase by Helical Peptides Corresponding to the Subunit Interface

    NASA Astrophysics Data System (ADS)

    Digard, Paul; Williams, Kevin P.; Hensley, Preston; Brooks, Ian S.; Dahl, Charles E.; Coen, Donald M.

    1995-02-01

    The herpes simplex virus DNA polymerase consists of two subunits-a catalytic subunit and an accessory subunit, UL42, that increases processivity. Mutations affecting the extreme C terminus of the catalytic subunit specifically disrupt subunit interactions and ablate virus replication, suggesting that new antiviral drugs could be rationally designed to interfere with polymerase heterodimerization. To aid design, we performed circular dichroism (CD) spectroscopy and analytical ultracentrifugation studies, which revealed that a 36-residue peptide corresponding to the C terminus of the catalytic subunit folds into a monomeric structure with partial α-helical character. CD studies of shorter peptides were consistent with a model where two separate regions of α-helix interact to form a hairpin-like structure. The 36-residue peptide and a shorter peptide corresponding to the C-terminal 18 residues blocked UL42-dependent long-chain DNA synthesis at concentrations that had no effect on synthesis by the catalytic subunit alone or by calf thymus DNA polymerase δ and its processivity factor. These peptides, therefore, represent a class of specific inhibitors of herpes simplex virus DNA polymerase that act by blocking accessory-subunit-dependent synthesis. These peptides or their structures may form the basis for the synthesis of clinically effective drugs.

  4. Relationship of herpes simplex encephalitis and transcranial direct current stimulation--a case report.

    PubMed

    Yang, Yuanbin; Xiao, Juan; Song, Haiqing; Wang, Ralph; Hussain, Mohammed; Song, Weiqun

    2015-04-01

    We report a rare case of relapsing herpes simplex encephalitis in a-37-year-old patient which was previously confirmed by positive polymerase chain reaction, herpes simplex virus (HSV) type1 IgG antibodies in cerebrospinal fluid and characterized on MRI. During the first admission, he was treated with continuous acyclovir treatment for one month with clinical improvement except for residual aphasia, for which he received a course of outpatient transcranial direct current stimulation (tDCS). A constant current of 1.2 mA was applied for 20 min twice daily. After the 4th day the patient was found to be irritable and uncooperative by staff and family members. A subsequent MRI showed significant deterioration of the lesion on comparison to the first MRI which led to discontinuation of tDCS.The relatively rapid exacerbation of HSV in only a few days is unusual. Our aim is to discuss if tDCS is related to HSV relapse and in doing so highlight possible mechanisms.

  5. Improving immunogenicity and efficacy of vaccines for genital herpes containing herpes simplex virus glycoprotein D.

    PubMed

    Awasthi, Sita; Shaw, Carolyn; Friedman, Harvey

    2014-12-01

    No vaccines are approved for prevention or treatment of genital herpes. The focus of genital herpes vaccine trials has been on prevention using herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) alone or combined with glycoprotein B. These prevention trials did not achieve their primary end points. However, subset analyses reported some positive outcomes in each study. The most recent trial was the Herpevac Trial for Women that used gD2 with monophosphoryl lipid A and alum as adjuvants in herpes simplex virus type 1 (HSV-1) and HSV-2 seronegative women. Unexpectedly, the vaccine prevented genital disease by HSV-1 but not HSV-2. Currently, HSV-1 causes more first episodes of genital herpes than HSV-2, highlighting the importance of protecting against HSV-1. The scientific community is conflicted between abandoning vaccine efforts that include gD2 and building upon the partial successes of previous trials. We favor building upon success and present approaches to improve outcomes of gD2-based subunit antigen vaccines.

  6. Morpho-anatomy and ontogeny of the underground system of Chrysolaena simplex (Less.) Dematt. (Asteraceae).

    PubMed

    Santos, Vanessa S; Souza, Vinicius P; Vilhalva, Divina A A; Ferreira, Fernanda P S; Paula, José R; Rezende, Maria Helena

    2016-03-01

    The occurrence of thickened underground systems in Asteraceae is widely reported in the literature. Given the great complexity of underground systems, which may originate from roots, stems, or both, morpho-anatomical analyses are essential to ensure the use of correct terminology. The goals of this study were to describe the morpho-anatomy and ontogeny, investigate the occurrence of secondary metabolites and evaluate the effects of seasonality on the underground system of Chrysolaena simplex (Less.) Dematt. Samples were studied using standard protocols of plant anatomy, scanning electron microscopy, histochemical and phytochemical. The underground system of C. simplex was categorised as a rhizophore which started from cotyledonary node. In adult individuals, with rhizophores completely developed, the primary roots degenerated and adventitious radicular systems are formed. The buds in the subterranean portions promote the rhizophore growing, and form aerial stems when exposed to light. Lipophilic droplets were evident in the parenchymatous cells of the cortex and pith, endodermis and buds. Inulin-type fructans were observed in the stem axis and buds of the rhizophore. The presence of buds, secondary metabolites and the storage of fructans and lipids in the rhizophore can be seen as adaptive traits. PMID:26871494

  7. Novel, Soluble Isoform of the Herpes Simplex Virus (HSV) Receptor Nectin1 (or PRR1-HIgR-HveC) Modulates Positively and Negatively Susceptibility to HSV Infection

    PubMed Central

    Lopez, Marc; Cocchi, Francesca; Avitabile, Elisa; Leclerc, Annouck; Adelaide, Jose; Campadelli-Fiume, Gabriella; Dubreuil, Patrice

    2001-01-01

    A novel member of the nectin family, nectin1γ, was molecularly cloned. The cDNA has the same ectodomain as nectin1α and nectin1β, the two known transmembrane isoforms that serve as receptors for herpes simplex virus (HSV) entry into human cell lines (nectin1α and nectin1β, also called PRR1-HveC and HIgR, respectively). The 1.4-kb transcript, which originated by alternative splicing, is expressed in human cell lines, and appears to have a narrow distribution in human tissues. The sequence does not have a hydrophobic anchoring region, and the protein is secreted in the culture medium of cells transfected with the cDNA. Nectin1γ, purified from culture medium, can compete with membrane-bound nectin1β and reduce HSV infectivity. The expression of nectin1γ cDNA in cells resistant to HSV infection and lacking HSV receptors enables HSV to enter the cell, which implies that it is present at the cell surface. Thus, nectin1γ has the potential both to mediate and to reduce HSV entry into cells. PMID:11356977

  8. Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System

    PubMed Central

    Li, Lihong; Li, Zhuoran; Wang, Erlin; Yang, Rui; Xiao, Yu; Han, Hongbo; Lang, Fengchao; Li, Xin; Xia, Yujie; Gao, Feng; Li, Qihan; Fraser, Nigel W.

    2015-01-01

    ABSTRACT Studies of herpes simplex virus (HSV) infections of humans are limited by the use of rodent models such as mice, rabbits, and guinea pigs. Tree shrews (Tupaia belangeri chinensis) are small mammals indigenous to southwest Asia. At behavioral, anatomical, genomic, and evolutionary levels, tree shrews are much closer to primates than rodents are, and tree shrews are susceptible to HSV infection. Thus, we have studied herpes simplex virus 1 (HSV-1) infection in the tree shrew trigeminal ganglion (TG) following ocular inoculation. In situ hybridization, PCR, and quantitative reverse transcription-PCR (qRT-PCR) analyses confirm that HSV-1 latently infects neurons of the TG. When explant cocultivation of trigeminal ganglia was performed, the virus was recovered after 5 days of cocultivation with high efficiency. Swabbing the corneas of latently infected tree shrews revealed that tree shrews shed virus spontaneously at low frequencies. However, tree shrews differ significantly from mice in the expression of key HSV-1 genes, including ICP0, ICP4, and latency-associated transcript (LAT). In acutely infected tree shrew TGs, no level of ICP4 was observed, suggesting the absence of infection or a very weak, acute infection compared to that of the mouse. Immunofluorescence staining with ICP4 monoclonal antibody, and immunohistochemistry detection by HSV-1 polyclonal antibodies, showed a lack of viral proteins in tree shrew TGs during both acute and latent phases of infection. Cultivation of supernatant from homogenized, acutely infected TGs with RS1 cells also exhibited an absence of infectious HSV-1 from tree shrew TGs. We conclude that the tree shrew has an undetectable, or a much weaker, acute infection in the TGs. Interestingly, compared to mice, tree shrew TGs express high levels of ICP0 transcript in addition to LAT during latency. However, the ICP0 transcript remained nuclear, and no ICP0 protein could be seen during the course of mouse and tree shrew TG

  9. Disparities in herpes simplex virus type 2 infection between black and white men who have sex with men in Atlanta, GA

    PubMed Central

    Okafor, Netochukwu; Rosenberg, Eli S; Luisi, Nicole; Sanchez, Travis; del Rio, Carlos; Sullivan, Patrick S; Kelley, Colleen F

    2015-01-01

    Summary Background HIV disproportionately affects black men who have sex with men, and herpes simplex virus type 2 is known to increase acquisition of HIV. However, data on racial disparities in herpes simplex virus type 2 prevalence and risk factors are limited among men who have sex with men in the United States. Methods InvolveMENt was a cohort study of black and white HIV-negative men who have sex with men in Atlanta, GA. Univariate and multivariate cross-sectional associations with herpes simplex virus type 2 seroprevalence were assessed among 455 HIV-negative men who have sex with men for demographic, behavioral, and social determinant risk factors using logistic regression. Results Seroprevalence of herpes simplex virus type 2 was 23% (48/211) for black and 16% (38/244) for white men who have sex with men (p = 0.05). Education, poverty, drug/alcohol use, incarceration, circumcision, unprotected anal intercourse, and condom use were not associated with herpes simplex virus type 2. In multivariate analyses, black race for those ≤25 years, but not >25 years, and number of sexual partners were significantly associated. Conclusions Young black men who have sex with men are disproportionately affected by herpes simplex virus type 2, which may contribute to disparities in HIV acquisition. An extensive assessment of risk factors did not explain this disparity in herpes simplex virus type 2 infection suggesting differences in susceptibility or partner characteristics. PMID:25246424

  10. Disparities in herpes simplex virus type 2 infection between black and white men who have sex with men in Atlanta, GA.

    PubMed

    Okafor, Netochukwu; Rosenberg, Eli S; Luisi, Nicole; Sanchez, Travis; del Rio, Carlos; Sullivan, Patrick S; Kelley, Colleen F

    2015-09-01

    HIV disproportionately affects black men who have sex with men, and herpes simplex virus type 2 is known to increase acquisition of HIV. However, data on racial disparities in herpes simplex virus type 2 prevalence and risk factors are limited among men who have sex with men in the United States. InvolveMENt was a cohort study of black and white HIV-negative men who have sex with men in Atlanta, GA. Univariate and multivariate cross-sectional associations with herpes simplex virus type 2 seroprevalence were assessed among 455 HIV-negative men who have sex with men for demographic, behavioural and social determinant risk factors using logistic regression. Seroprevalence of herpes simplex virus type 2 was 23% (48/211) for black and 16% (38/244) for white men who have sex with men (p = 0.05). Education, poverty, drug/alcohol use, incarceration, circumcision, unprotected anal intercourse, and condom use were not associated with herpes simplex virus type 2. In multivariate analyses, black race for those ≤25 years, but not >25 years, and number of sexual partners were significantly associated. Young black men who have sex with men are disproportionately affected by herpes simplex virus type 2, which may contribute to disparities in HIV acquisition. An extensive assessment of risk factors did not explain this disparity in herpes simplex virus type 2 infection suggesting differences in susceptibility or partner characteristics.

  11. Penile herpes simplex virus type 1 infection presenting two and a half years after Jewish ritual circumcision of an infant.

    PubMed

    Yossepowitch, Orit; Gottesman, Tamar; Schwartz, Orna; Stein, Michal; Serour, Francis; Dan, Michael

    2013-06-01

    The association between Jewish ritual circumcision and genital herpes simplex virus type 1 infection has been well described. We report a case of genital herpes that first presented at the age of 2½ years. We believe that the infection was acquired asymptomatically through direct orogenital suction performed during circumcision in the newborn period.

  12. Evaluation of new transport medium for detection of herpes simplex virus by culture and direct enzyme-linked immunosorbent assay.

    PubMed

    Ogburn, J R; Hoffpauir, J T; Cole, E; Hood, K; Michael, D; Nguyen, T; Raden, S; Raju, B; Reisinger, V; Oefinger, P E

    1994-12-01

    The transport medium Multi-Microbe Media (M4) was evaluated prospectively by culture and direct enzyme-linked immunosorbent assay (ELISA) for detection of herpes simplex virus from 473 specimens. In addition, 377 specimens in Bartels Viral Transport Medium were evaluated. By using culture as a "gold standard," the ELISA sensitivity was approximately 85%, while the specificities exceeded 96% for both media.

  13. Herpes simplex type 1 defective interfering particles do not affect the antiviral activity of acyclovir, foscarnet and adenine arabinoside.

    PubMed

    Harmenberg, J G; Svensson, L T

    1988-03-01

    The concentration of defective interfering particles (DI-particles) of herpes simplex type 1 virus was analysed by electron microscopy and plaque titration. Fifteen consecutive passages of undiluted virus in green monkey kidney cells were followed. No relationship was found between the concentration of DI-particles and the activity of antiviral substances such as acyclovir, foscarnet and adenine arabinoside.

  14. Mutations in the herpes simplex virus DNA polymerase gene can confer resistance to 9-beta-D-arabinofuranosyladenine.

    PubMed Central

    Coen, D M; Furman, P A; Gelep, P T; Schaffer, P A

    1982-01-01

    Mutants of herpes simplex virus type 1 resistant to the antiviral drug 9-beta-D-arabinofuranosyladenine (araA) have been isolated and characterized. AraA-resistant mutants can be isolated readily and appear at an appreciable frequency in low-passage stocks of wild-type virus. Of 13 newly isolated mutants, at least 11 were also resistant to phosphonoacetic acid (PAA). Of four previously described PAA-resistant mutants, two exhibited substantial araA resistance. The araA resistance phenotype of one of these mutants, PAAr5, has been mapped to the HpaI-B fragment of herpes simplex virus DNA by marker transfer, and araA resistance behaved in marker transfer experiments as if it were closely linked to PAA resistance, a recognized marker for the viral DNA polymerase locus. PAAr5 induced viral DNA polymerase activity which was much less susceptible to inhibition by the triphosphate derivative of araA than was wild-type DNA polymerase. These genetic and biochemical data indicate that the herpes simplex virus DNA polymerase gene is a locus which, when mutated, can confer resistance to araA and thus that the herpes simplex virus DNA polymerase is a target for this antiviral drug. PMID:6284981

  15. Infection of human peripheral blood mononuclear cells with a temperature-sensitive mutant of measles virus.

    PubMed Central

    Vydelingum, S; Ilonen, J; Salonen, R; Marusyk, R; Salmi, A

    1989-01-01

    A stable temperature-sensitive mutant of measles virus (MV ts38) was used to study the mechanism of virus-mediated immune suppression of peripheral blood mononuclear cells in vitro. Both unstimulated and phytohemagglutinin-stimulated cultures released infectious virus at 32 degrees C, whereas no virus was released at 37 degrees C, although both viral RNA and viral proteins were synthesized. However, the response of the lymphoid cells to phytohemagglutinin, concanavalin A, and herpes simplex virus antigen was decreased in the presence of MV ts38 at 37 degrees C. The viability of infected cells was not diminished, therefore excluding cell death as a reason for immunosuppression. Interleukin 2 did not play a role in the inhibitory effect of MV ts38. Antibodies to alpha interferon partially reversed the inhibitory effect of the virus infection on lymphocyte mitogenesis, thus implying that alpha interferon plays a role in the immunosuppression. Depletion experiments indicated that adherent cells play a greater role in the measles virus-induced immunosuppression than nonadherent cells. However, monocyte maturation to macrophages had no effect on the degree of immunosuppression. Images PMID:2911119

  16. 3D radiative transfer in colliding wind binaries: Application of the SimpleX algorithm to 3D SPH simulations

    NASA Astrophysics Data System (ADS)

    Madura, Thomas; Clementel, Nicola; Kruip, Chael; Icke, Vincent; Gull, Theodore

    2014-09-01

    We present the first results of full 3D radiative transfer simulations of the colliding stellar winds in a massive binary system. We accomplish this by applying the SIMPLEX algorithm for 3D radiative transfer on an unstructured Delaunay grid to recent 3D smoothed particle hydrodynamics (SPH) simulations of the colliding winds in the binary system η Carinae. We use SIMPLEX to obtain detailed ionization fractions of hydrogen and helium, in 3D, at the resolution of the original SPH simulations. We show how the SIMPLEX simulations can be used to generate synthetic spectral data cubes for comparison to data obtained with the Hubble Space Telescope (HST)/Space Telescope Imaging Spectrograph as part of a multi-cycle program to map changes in η Car's extended interacting wind structures across one binary cycle. Comparison of the HST observations to the SIMPLEX models can help lead to more accurate constraints on the orbital, stellar, and wind parameters of the η Car system, such as the primary's mass-loss rate and the companion's temperature and luminosity. While we initially focus specifically on the η Car binary, the numerical methods employed can be applied to numerous other colliding wind (WR140, WR137, WR19) and dusty 'pinwheel' (WR104, WR98a) binary systems. One of the biggest remaining mysteries is how dust can form and survive in such systems that contain a hot, luminous O star. Coupled with 3D hydrodynamical simulations, SIMPLEX simulations have the potential to help determine the regions where dust can form and survive in these unique objects.

  17. Herpes Simplex

    MedlinePlus

    ... Health Services Resident Rotation Resident International Grant Shade Structure Program SPOTme® Skin Cancer Screening Program Volunteer Recognition ... Basement Membrane Zone lecture Full lecture Part 1: Structure Part 2: Origin Part 3: Function Textbook Study ...

  18. Interaction of herpes simplex virus with mononuclear phagocytes is dependent on the differentiation stage of the cells.

    PubMed

    Bruun, T; Kristoffersen, A K; Rollag, H; Degré, M

    1998-02-01

    The interaction of herpes simplex virus (HSV) with mononuclear phagocytes (MP), i.e. monocytes and macrophages, is of importance for the pathogenesis of HSV infections. MP are known to play a significant role in the cellular defence against infections with HSV, but it has also been shown that HSV-1 affects MP. The infection of these cells at different stages of differentiation has different outcomes, and may result in the alteration of important cellular functions. HSV-1 inhibits the morphological differentiation of human monocytes, and this inhibition occurs in spite of the fact that human monocytes are non-permissive to HSV-1. We have studied the effect of HSV infection of monocytes and macrophages on production of essential cytokines and related this effect to the reproduction of the virus. Blood-derived MP were cultured in vitro and inoculated with HSV at different stages of differentiation. Replication of the virus was measured by infectivity titration, detection of HSV antigens by immunofluorescence and detection of HSV-specific mRNA. In monocytes, no viral replication and no production of late protein was seen. HSV IE gene was transcribed in monocytes from some donors, but not from others. In macrophages, virus replicated, but less efficiently than in fully permissive fibroblast cells. The production of IL-1 beta, IL-6 and TNF-alpha in both non-permissive monocytes and permissive macrophages was assayed both at the transcriptional level, as mRNA, and as protein released from the cells. Production of cytokines by MP was affected by HSV-1. The level of cytokine mRNA and cytokine protein did not correspond for all cytokines, which may suggest that translational regulation and/or cytokine inhibitors are important in the regulation of the cytokine response. The cytokine modulation, both at the transcriptional level and measured as biological activity, was different in monocytes and macrophages, and varied between different donors. Our results indicate a relation

  19. Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING, viral mRNAs, and microRNAs

    PubMed Central

    Kalamvoki, Maria; Du, Te; Roizman, Bernard

    2014-01-01

    STING (stimulator of IFN genes) activates the IFN-dependent innate immune response to infection on sensing the presence of DNA in cytosol. The quantity of STING accumulating in cultured cells varies; it is relatively high in some cell lines [e.g., HEp-2, human embryonic lung fibroblasts (HEL), and HeLa] and low in others (e.g., Vero cells). In a preceding publication we reported that STING was stable in four cell lines infected with herpes simplex virus 1 and that it was actively stabilized in at least two cell lines derived from human cancers. In this report we show that STING is exported from HEp-2 cells to Vero cells along with virions, viral mRNAs, microRNAs, and the exosome marker protein CD9. The virions and exosomes copurified. The quantity of STING and CD9 exported from one cell line to another was inoculum-size–dependent and reflected the levels of STING and CD9 accumulating in the cells in which the virus inoculum was made. The export of STING, an innate immune sensor, and of viral mRNAs whose major role may be in silencing viral genes in latently infected neurons, suggests that the virus has evolved mechanisms that curtail rather than foster the spread of infection under certain conditions. PMID:25368198

  20. Measuring sexual selection on females in sex-role-reversed Mormon crickets (Anabrus simplex, Orthoptera: Tettigoniidae).

    PubMed

    Robson, L J; Gwynne, D T

    2010-07-01

    Although many studies examine the form of sexual selection in males, studies characterizing this selection in females remain sparse. Sexual selection on females is predicted for sex-role-reversed Mormon crickets, Anabrus simplex, where males are choosy of mates and nutrient-deprived females compete for matings and nutritious nuptial gifts. We used selection analyses to describe the strength and form of sexual selection on female morphology. There was no positive linear sexual selection on the female body size traits predicted to be associated with male preferences and female competition. Instead, we detected selection for decreasing head width and mandible length, with stabilizing selection as the dominant form of nonlinear selection. Additionally, we tested the validity of a commonly used instantaneous measure of mating success by comparing selection results with those determined using cumulative mating rate. The two fitness measures yielded similar patterns of selection, supporting the common sampling method comparing mated and unmated fractions.

  1. A new simplex chemometric approach to identify olive oil blends with potentially high traceability.

    PubMed

    Semmar, N; Laroussi-Mezghani, S; Grati-Kamoun, N; Hammami, M; Artaud, J

    2016-10-01

    Olive oil blends (OOBs) are complex matrices combining different cultivars at variable proportions. Although qualitative determinations of OOBs have been subjected to several chemometric works, quantitative evaluations of their contents remain poorly developed because of traceability difficulties concerning co-occurring cultivars. Around this question, we recently published an original simplex approach helping to develop predictive models of the proportions of co-occurring cultivars from chemical profiles of resulting blends (Semmar & Artaud, 2015). Beyond predictive model construction and validation, this paper presents an extension based on prediction errors' analysis to statistically define the blends with the highest predictability among all the possible ones that can be made by mixing cultivars at different proportions. This provides an interesting way to identify a priori labeled commercial products with potentially high traceability taking into account the natural chemical variability of different constitutive cultivars.

  2. Expression, Purification, Crystallization And Preliminary X-Ray Studies of Histamine Dehydrogenase From Nocardioides Simplex

    SciTech Connect

    Reed, T.M.; Hirakawa, H.; Mure, M.; Scott, E.E.; Limburg, J.

    2009-05-21

    Histamine dehydrogenase (HADH) from Nocardioides simplex catalyzes the oxidative deamination of histamine to produce imidazole acetaldehyde and an ammonium ion. HADH is functionally related to trimethylamine dehydrogenase (TMADH), but HADH has strict substrate specificity towards histamine. HADH is a homodimer, with each 76 kDa subunit containing two redox cofactors: a [4Fe-4S] cluster and an unusual covalently bound flavin mononucleotide, 6-S-cysteinyl-FMN. In order to understand the substrate specificity of HADH, it was sought to determine its structure by X-ray crystallography. This enzyme has been expressed recombinantly in Escherichia coli and successfully crystallized in two forms. Diffraction data were collected to 2.7 {angstrom} resolution at the SSRL synchrotron with 99.7% completeness. The crystals belonged to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 101.14, b = 107.03, c = 153.35 {angstrom}.

  3. Hemorrhagic and ischemic stroke secondary to herpes simplex virus type 2 meningitis and vasculopathy.

    PubMed

    Snider, Samuel B; Jacobs, Claire S; Scripko, Patricia S; Klein, Joshua P; Lyons, Jennifer L

    2014-08-01

    Herpes simplex virus type 2 (HSV-2) meningitis dogmatically is benign and self-limited in the immune competent patient. However, we describe how left untreated HSV-2 meningitis can be complicated by vasculitis and both ischemic and hemorrhagic stroke. We report a 57-year-old woman with lymphocytic meningitis complicated by ischemic stroke and intracerebral hemorrhage in the setting of vasculopathy and HSV-2 DNA detected in CSF successfully treated with acyclovir and corticosteroids. Subsequent angiographic magnetic resonance imaging revealed improvement in the vasculopathy after treatment. This case demonstrates that HSV-2 meningitis may take a less benign course and further provides the first evidence of angiographic improvement in addition to clinical improvement after definitive treatment.

  4. Perfusion and thallium single photon emission computed tomography in herpes simplex encephalitis.

    PubMed

    De Deyn, P P; Van den Broucke, P W; Pickut, B A; Appel, B; Crols, R; Cras, P; Martin, J J

    1998-04-15

    This is the first report on 201thallium-single photon emission computed tomography (201Tl-SPECT) brain scan of a patient with herpes simplex encephalitis (HSE). The presented 201Tl-SPECT observations are correlated with 99mtechnetium hexamethylpropylene amine oxime (99mTc-HMPAO) perfusion SPECT and magnetic resonance imaging (MRI) findings. Brain 99mTc-HMPAO perfusion SPECT reveals a hyperperfusion in the right temporal lobe with extension to the parietal lobe and a hypoperfusion in the ipsilateral occipital lobe. 201Tl-SPECT shows a fixation in the right temporal lobe coinciding with the gadolinium enhancement on MRI. The right occipital lesion shown by gadolinium captation on MRI and hypoperfusion on 99mTc-HMPAO perfusion SPECT was not evident on the 201Tl SPECT. These findings could illustrate that the lesions might be different pathophysiologically.

  5. 3'-Amino thymidine affinity matrix for the purification of herpes simplex virus thymidine kinase.

    PubMed Central

    Tung, P. P.; Respass, J.; Summers, W. C.

    1996-01-01

    A simple procedure for preparation of an affinity resin with 3'-amino thymidine linked to the carboxyl residues on 6-amino-hexanoic agarose is described. We have used this column for a rapid and simple purification of the thymidine kinase encoded by the herpes simplex virus type 1 genome. This resin has two major advantages over the most widely use used resin made with thymidine-p-nitrophenyl phosphate: first it is easily obtainable, and second, it is not subject to destruction by phosphodiesterases. The two resins are very similar in behavior and the resin made with amino thymidine has allowed us to prepare large quantities of highly purified HSV TK for crystallization studies. Images Figure 3 Figure 4 PMID:9436293

  6. Does the cognitive architecture of simplex and multiplex ASD families differ?

    PubMed

    Oerlemans, Anoek M; Hartman, Catharina A; Franke, Barbara; Buitelaar, Jan K; Rommelse, Nanda N J

    2016-02-01

    Children with an autism spectrum disorder (ASD) and their unaffected siblings from 54 simplex (SPX, one individual in the family affected) and 59 multiplex (MPX, two or more individuals affected) families, and 124 controls were assessed on intelligence, social cognition and executive functions. SPX and MPX ASD probands displayed similar cognitive profiles, but within-family contrasts were highest in SPX families, suggesting SPX-MPX stratification may help parse etiological heterogeneity of ASD. Unaffected siblings (regardless SPX or MPX) were mostly unimpaired, suggesting that cognitive problems may be part of the defining features of ASD, rather than being an endophenotypic trait. Except for affective prosody, which appeared to be the most sensitive cognitive marker for detecting familial risk for ASD. PMID:26340958

  7. Incidental Detection of Hairy Cell Leukaemia with Herpes Simplex Virus (HSV) Related Lip Ulcer Mimicking Carcinoma.

    PubMed

    Agrawal, Pallavi; Bhartiya, Richa; Singh, Ran Vijoy Narayan

    2016-08-01

    Hairy cell leukemia is a chronic lympho-proliferative disease. It is indolent but progressive in nature. It arises from B-cell lineage. We report an incidentally detected case of Hairy Cell Leukaemia (HCL) in a 55-year-old male patient with Herpes simplex virus (HSV) - related lip ulcer mimicking squamous cell carcinoma. Clinically the patient presented with lip ulceration without pain. He was found to have moderate hepatosplenomegaly and pancytopenia on general examination. Bone marrow aspiration and flow cytometric immunophenotyping revealed HCL. The oral lesion resolved after antiviral therapy. The intriguing possibility of a combined pathogenesis for the two disorders is considered, as HCL is known to be associated with immunosuppression, second malignancies and the production of cytokines promoting epithelial growth. PMID:27656454

  8. Cell-mediated immunity against herpes simplex induction of cytotoxic T lymphocytes.

    PubMed Central

    Lawman, M J; Rouse, B T; Courtney, R J; Walker, R D

    1980-01-01

    The conditions required for the induction of both primary cytotoxic T lymphocytes (CTL) in vivo and secondary CTL in vitro against herpes simplex virus type 1 (HSV-1)-infected cells were defined. Primary CTL responses occurred only in mice exposed to infectious HSV-1. These responses, which were shown to be mediated by T lymphocytes, peaked at 1 week and had disappeared by 2 weeks after infection. The level of primary cytotoxicity was enhanced by treatment of mice with cyclophosphamide before infection. Secondary in vitro CTL responses were more pronounced and were induced by some forms of inactivated virus as well as by infectious HSV-1. Thus, both ultraviolet light- and glutaraldehyde-inactivated preparations of HSV-1 induced CTL, but heat-inactivated and detergent-extracted antigens failed to do so. The reasons for the differing efficiency of infectious and noninfectious HSV-1 for induction of CTL are discussed. PMID:6244225

  9. Herpes simplex virus infection in burned patients: epidemiology of 11 cases.

    PubMed

    Bourdarias, B; Perro, G; Cutillas, M; Castede, J C; Lafon, M E; Sanchez, R

    1996-06-01

    Burned patients suffer significant immunosuppression during the first 3 or 4 weeks after hospitalization. Herpes simplex virus (HSV) infections are commonly seen in immunosuppressed patients and may account for considerable morbidity and some mortality. We studied retrospectively 11 patients with severe burn injury who became infected with HSV. We determined the prevalence of viral infection in this group of patients. Serological testing and viral culture was used to diagnose HSV infection. No general complications appeared in these 11 patients in association with HSV but two patients died of multiorgan failure. Locally, areas of active epidermal regeneration were most commonly affected. Acyclovir therapy was not used and the duration of hospitalization was normal in these 11 patients.

  10. Herpes simplex virus 1 induces egress channels through marginalized host chromatin.

    PubMed

    Myllys, Markko; Ruokolainen, Visa; Aho, Vesa; Smith, Elizabeth A; Hakanen, Satu; Peri, Piritta; Salvetti, Anna; Timonen, Jussi; Hukkanen, Veijo; Larabell, Carolyn A; Vihinen-Ranta, Maija

    2016-01-01

    Lytic infection with herpes simplex virus type 1 (HSV-1) induces profound modification of the cell nucleus including formation of a viral replication compartment and chromatin marginalization into the nuclear periphery. We used three-dimensional soft X-ray tomography, combined with cryogenic fluorescence, confocal and electron microscopy, to analyse the transformation of peripheral chromatin during HSV-1 infection. Our data showed an increased presence of low-density gaps in the marginalized chromatin at late infection. Advanced data analysis indicated the formation of virus-nucleocapsid-sized (or wider) channels extending through the compacted chromatin of the host. Importantly, confocal and electron microscopy analysis showed that these gaps frequently contained viral nucleocapsids. These results demonstrated that HSV-1 infection induces the formation of channels penetrating the compacted layer of cellular chromatin and allowing for the passage of progeny viruses to the nuclear envelope, their site of nuclear egress. PMID:27349677

  11. A further study on relationships between herpes simplex virus and Bovid herpesvirus-2.

    PubMed

    Castrucci, G; Ferrari, M; Frigeri, F; Aldrovandi, V

    1990-04-01

    Calves exposed by intravenous or intradermal inoculation with Herpes simplex virus (HSV), types 1 and 2, remained clinically normal and HSV was not recovered from nasal secretion nor blood samples. However, the clinical response of calves pre-inoculated with HSV, to Bovid herpesvirus-2 (BH-2) challenge infection was much milder than that in the challenge control calves, and the titer of BHV-2 by skin titration underwent a significant (2-2.5 log units) reduction in the HSV pre-inoculated calves. Inoculation of calves with live HSV provided a much greater protection against BHV-2 challenge infection compared with the results of previous experiments in which a Triton X100-inactivated HSV antigen was used. It was speculated that the possibility of HSV replicating in cattle must still be considered an open question.

  12. Does the cognitive architecture of simplex and multiplex ASD families differ?

    PubMed

    Oerlemans, Anoek M; Hartman, Catharina A; Franke, Barbara; Buitelaar, Jan K; Rommelse, Nanda N J

    2016-02-01

    Children with an autism spectrum disorder (ASD) and their unaffected siblings from 54 simplex (SPX, one individual in the family affected) and 59 multiplex (MPX, two or more individuals affected) families, and 124 controls were assessed on intelligence, social cognition and executive functions. SPX and MPX ASD probands displayed similar cognitive profiles, but within-family contrasts were highest in SPX families, suggesting SPX-MPX stratification may help parse etiological heterogeneity of ASD. Unaffected siblings (regardless SPX or MPX) were mostly unimpaired, suggesting that cognitive problems may be part of the defining features of ASD, rather than being an endophenotypic trait. Except for affective prosody, which appeared to be the most sensitive cognitive marker for detecting familial risk for ASD.

  13. Midtrimester fetal herpes simplex-2 diagnosis by serology, culture and quantitative polymerase chain reaction.

    PubMed

    Curtin, William M; Menegus, Marilyn A; Patru, Maria-Magdalena; Peterson, C Jeanne; Metlay, Leon A; Mooney, Robert A; Stanwood, Nancy L; Scheible, Amy L; Dorgan, Angela

    2013-01-01

    The acquisition of herpes simplex virus (HSV) in utero comprises a minority of neonatal herpes infections. Prenatal diagnosis is rare. We describe a midtrimester diagnosis of fetal HSV-2 infection. Ultrasound at 20 weeks for elevated maternal serum α-fetoprotein (MSAFP) showed lagging fetal growth, echogenic bowel, echogenic myocardium, and liver with a mottled pattern of echogenicity. Amniocentesis demonstrated normal karyotype, elevated AFP and positive acetylcholinesterase. Culture isolated HSV-2 with an aberrant growth pattern. Maternal serology was positive for HSV-2. Quantitative DNA polymerase chain reaction (PCR) showed 59 million copies/ml. Fetal autopsy demonstrated widespread tissue necrosis but only sparse HSV-2 inclusions. Fetal HSV-2 infection can be suspected when an elevated MSAFP accompanies ultrasound findings suggesting perinatal infection. Maternal HSV serology, amniotic fluid culture and quantitative PCR are recommended for diagnostic certainty and counseling.

  14. Near instrument-free, simple molecular device for rapid detection of herpes simplex viruses.

    PubMed

    Lemieux, Bertrand; Li, Ying; Kong, Huimin; Tang, Yi-Wei

    2012-06-01

    The first near instrument-free, inexpensive and simple molecular diagnostic device (IsoAmp HSV, BioHelix Corp., MA, USA) recently received US FDA clearance for use in the detection of herpes simplex viruses (HSV) in genital and oral lesion specimens. The IsoAmp HSV assay uses isothermal helicase-dependent amplification in combination with a disposable, hermetically-sealed, vertical-flow strip identification. The IsoAmp HSV assay has a total test-to-result time of less than 1.5 h by omitting the time-consuming nucleic acid extraction. The diagnostic sensitivity and specificity are comparable to PCR and are superior to culture-based methods. The near instrument-free, rapid and simple characteristics of the IsoAmp HSV assay make it potentially suitable for point-of-care testing.

  15. New concepts in herpes simplex virus vaccine development: notes from the battlefield.

    PubMed

    Dasgupta, Gargi; Chentoufi, Aziz A; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

    2009-08-01

    The recent discovery that T cells recognize different sets of herpes simplex virus type 1 and type 2 epitopes from seropositive symptomatic and asymptomatic individuals might lead to a fundamental immunologic advance in vaccine development against herpes infection and diseases. The newly introduced needle-free mucosal (i.e., topical ocular and intravaginal) lipopeptide vaccines provide a novel strategy that might target ocular and genital herpes and possibly provide 'heterologous protection' from HIV-1. Indeed, mucosal self-adjuvanting lipopeptide vaccines are easy to manufacture, simple to characterize, extremely pure, cost-effective, highly immunogenic and safe. In this review, we bring together recent published and unpublished data that illuminates the status of epitope-based herpes vaccine development and present an overview of our recent approach to an 'asymptomatic epitope'-based lipopeptide vaccine.

  16. High GC content of simple sequence repeats in Herpes simplex virus type 1 genome.

    PubMed

    Ouyang, Qingjian; Zhao, Xiangyan; Feng, Haiping; Tian, You; Li, Dan; Li, Mingfu; Tan, Zhongyang

    2012-05-10

    The presence, locations and composition of simple sequence repeats (SSRs) in Herpes simplex virus type 1 (HSV-1) genome were extracted and analyzed by using the software Imperfect Microsatellite Extractor (IMEx). There were 663 mon-, 502 di-, 184 tri-, 20 tetra-, 4 penta- and 4 hexanucleotide SSRs that were observed in different distribution between coding and noncoding regions in the HSV-1 genome. G/C, GC/CG, and (GGC)(n) were predominant in mononucleotide, dinucletide, trinucleotide repeats respectively. Indeed, the results showed that GC content in simple sequence repeats was notably higher than that in entire HSV-1 genome. Our data might be helpful for studying the pathogenesis, genome structure and evolution of HSV-1.

  17. Ultrastructural studies on the replication of herpes simplex virus in PK and XTC-2 cells.

    PubMed

    Ciampor, F; Szántó, J

    1982-01-01

    Ultrastructural changes showed the following characteristics of restricted replication of herpes simplex virus 1 (HSV 1) strains MA and HSZP in PK and XTC-2 cells: 1) minimal cytopathic changes in PK cells as compared to more pronounced alterations in XTC-2 cells; 2) formation of single nucleocapsids or their absence in the nuclei of PK cells infected with the HSZP strain; 3) lack of budding and envelopment and absence of reduplication of the nuclear membrane; 4) persistence of partially uncoated virions within the endocytic vacuoles in the cytoplasm of PK cells; and 5) formation of dense inclusion bodies in addition to the presence of defective virions in the cytoplasm of XTC-2 cells and vacuolation of their cytoplasmic membranes. The replication of HSV 1 in PK and XTC-2 cells seemed to be blocked at both early and late stages of virus replication. At low multiplicity of infection, no virus particles were formed.

  18. Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans

    PubMed Central

    1992-01-01

    The role of cell surface heparan sulfate in herpes simplex virus (HSV) infection was investigated using CHO cell mutants defective in various aspects of glycosaminoglycan synthesis. Binding of radiolabeled virus to the cells and infection were assessed in mutant and wild-type cells. Virus bound efficiently to wild-type cells and initiated an abortive infection in which immediate-early or alpha viral genes were expressed, despite limited production of late viral proteins and progeny virus. Binding of virus to heparan sulfate-deficient mutant cells was severely impaired and mutant cells were resistant to HSV infection. Intermediate levels of binding and infection were observed for a CHO cell mutant that produced undersulfated heparan sulfate. These results show that heparan sulfate moieties of cell surface proteoglycans serve as receptors for HSV. PMID:1310996

  19. Spectroscopic investigation of herpes simplex viruses infected cells and their response to antiviral therapy

    NASA Astrophysics Data System (ADS)

    Erukhimovitch, Vitaly; Talyshinsky, Marina; Souprun, Yelena; Huleihel, Mahmoud

    2006-07-01

    In the present study, we used microscopic Fourier transform infrared spectroscopy (FTIR) to evaluate the antiviral activity of known antiviral agents against herpes viruses. The antiviral activity of Caffeic acid phenethyl ester (CAPE) (which is an active compound of propolis) against herpes simplex type 1 and 2 was examined in cell culture. The advantage of microscopic FTIR spectroscopy over conventional FTIR spectroscopy is that it facilitates inspection of restricted regions of cell culture or tissue. Our results showed significant spectral differences at early stages of infection between infected and non-infected cells, and between infected cells treated with the used antiviral agent and those not treated. In infected cells, there was a considerable increase in phosphate levels. Our results show that treatment with used antiviral agent considerably abolish the spectral changes induced by the viral infection. In addition, it is possible to track by FTIR microscopy method the deferential effect of various doses of the drug.

  20. Recombination Promoted by DNA Viruses: Phage λ to Herpes Simplex Virus

    PubMed Central

    Weller, Sandra K.; Sawitzke, James A.

    2015-01-01

    The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies. PMID:25002096