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  1. Herpes Simplex

    MedlinePlus

    ... is an infection that is caused by a herpes simplex virus (HSV). Oral herpes causes cold sores around the mouth or face. ... affects the genitals, buttocks or anal area. Other herpes infections can affect the eyes, skin, or other parts of the body. The virus can be dangerous in newborn babies or in ...

  2. 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 ...

  3. Serum herpes simplex antibodies

    MedlinePlus

    ... gov/ency/article/003352.htm Serum herpes simplex antibodies To use the sharing features on this page, please enable JavaScript. Serum herpes simplex antibodies is a blood test that looks for antibodies ...

  4. Concurrent chemotherapy inhibits Herpes simplex virus 1 replication and oncolysis

    PubMed Central

    Kulu, Yakup; Kawasaki, Hiroshi; Donahue, James M.; Kasuya, Hideki; Cusack, James C.; Choi, Enid W.; Kuruppu, Darshini K.; Fuchs, Bryan C.; Tanabe, Kenneth K.

    2013-01-01

    Herpes simplex virus 1 (HSV-1) replication in cancer cells leads to their destruction (viral oncolysis) and has been under investigation as an experimental cancer therapy in clinical trials as single agents, and as combinations with chemotherapy. Cellular responses to chemotherapy modulate viral replication, but these interactions are poorly understood. To investigate the effect of chemotherapy on HSV-1 oncolysis, viral replication in cells exposed to 5-fluorouracil (5-FU), irinotecan (CPT-11), methotrexate (MTX) or a cytokine (TNF-α) was examined. Exposure of colon and pancreatic cancer cells to 5-FU, CPT-11, or MTX in vitro significantly antagonizes both HSV-1 replication and lytic oncolysis. Nuclear factor-kappa B (NF-κB) activation is required for efficient viral replication, and experimental inhibition of this response with an IκBα dominant-negative repressor significantly antagonizes HSV-1 replication. Nonetheless cells exposed to 5-FU, CPT-11, TNF-α or HSV-1 activate NF-κB. Cells exposed to MTX do not activate NF-κB, suggesting a possible role for NF-κB inhibition in the decreased viral replication observed following exposure to MTX. The role of eukaryotic initiation factor 2 alpha (eIF-2α) dephosphorylation was examined; HSV-1 mediated eIF-2α dephosphorylation proceeds normally in HT29 cells exposed to 5-FU-, CPT-11-, or MTX. This report demonstrates that cellular responses to chemotherapeutic agents provide an unfavorable environment for HSV-1-mediated oncolysis, and these observations are relevant to the design of both preclinical and clinical studies of HSV-1 oncolysis. PMID:23348635

  5. Serum herpes simplex antibodies

    MedlinePlus

    ... when it detects harmful substances such as the herpes virus. This test does not detect the virus itself. ... Philadelphia, PA: Elsevier; 2014:chap 308. Whitley RJ. Herpes simplex virus infections In: Goldman L, Schafer AI, eds. Goldman's ...

  6. Inhibition of topoisomerase II by ICRF-193 prevents efficient replication of herpes simplex virus type 1.

    PubMed Central

    Hammarsten, O; Yao, X; Elias, P

    1996-01-01

    Cellular topoisomerase II is specifically inactivated by the drug ICRF-193. This compound turns topoisomerase II into a closed clamp that is unable to cleave DNA. We have investigated the effects of this inhibitor on the replication of herpes simplex virus type 1. We show that ICRF-193 at low multiplicities of infection dramatically inhibits viral DNA synthesis and the production of infectious virus. The inhibition is less efficient at high multiplicities of infection. In addition, inhibition of viral DNA synthesis was observed only when ICRF-193 was present during the first 4 h of the infectious cycle. The transient replication of plasmids containing a herpes simplex virus type 1 origin of DNA replication, oriS, was affected by ICRF-193 in the same way. In contrast, neither cellular DNA synthesis nor replication of plasmids containing a simian virus 40 origin of DNA replication was inhibited. The observed effect on herpes simplex virus DNA replication was not caused by a decreased transcription of replication genes inasmuch as the levels of UL8, UL9, UL29, and UL30 rmRNAs were unaffected by the drug. These results suggest that topoisomerase II plays a vital role during the replication of herpes simplex virus type 1 DNA. We speculate that topoisomerase II is involved in the decatenation of newly synthesized daughter molecules. PMID:8676478

  7. 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 ...

  8. Nongenital herpes simplex virus.

    PubMed

    Usatine, Richard P; Tinitigan, Rochelle

    2010-11-01

    Nongenital herpes simplex virus type 1 is a common infection usually transmitted during childhood via nonsexual contact. Most of these infections involve the oral mucosa or lips (herpes labialis). The diagnosis of an infection with herpes simplex virus type 1 is usually made by the appearance of the lesions (grouped vesicles or ulcers on an erythematous base) and patient history. However, if uncertain, the diagnosis of herpes labialis can be made by viral culture, polymerase chain reaction, serology, direct fluorescent antibody testing, or Tzanck test. Other nonoral herpes simplex virus type 1 infections include herpetic keratitis, herpetic whitlow, herpes gladiatorum, and herpetic sycosis of the beard area. The differential diagnosis of nongenital herpes simplex virus infection includes aphthous ulcers, acute paronychia, varicella-zoster virus infection, herpangina, herpes gestationis (pemphigoid gestationis), pemphigus vulgaris, and Behçet syndrome. Oral acyclovir suspension is an effective treatment for children with primary herpetic gingivostomatitis. Oral acyclovir, valacyclovir, and famciclovir are effective in treating acute recurrence of herpes labialis (cold sores). Recurrences of herpes labialis may be diminished with daily oral acyclovir or valacyclovir. Topical acyclovir, penciclovir, and docosanol are optional treatments for recurrent herpes labialis, but they are less effective than oral treatment. PMID:21121552

  9. Role for herpes simplex virus 1 ICP27 in the inhibition of type I interferon signaling

    SciTech Connect

    Johnson, Karen E.; Song, Byeongwoon; Knipe, David M.

    2008-05-10

    Host cells respond to viral infection by many mechanisms, including the production of type I interferons which act in a paracrine and autocrine manner to induce the expression of antiviral interferon-stimulated genes (ISGs). Viruses have evolved means to inhibit interferon signaling to avoid induction of the innate immune response. Herpes simplex virus 1 (HSV-1) has several mechanisms to inhibit type I interferon production, the activities of ISGs, and the interferon signaling pathway itself. We report that the inhibition of the Jak/STAT pathway by HSV-1 requires viral gene expression and that viral immediate-early protein ICP27 plays a role in downregulating STAT-1 phosphorylation and in preventing the accumulation of STAT-1 in the nucleus. We also show that expression of ICP27 by transfection causes an inhibition of IFN-induced STAT-1 nuclear accumulation. Therefore, ICP27 is necessary and sufficient for at least some of the effects of HSV infection on STAT-1.

  10. Oligonucleotides Designed to Inhibit TLR9 Block Herpes Simplex Virus type 1 Infection at Multiple Steps

    PubMed Central

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

    2014-01-01

    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 (TLR) 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 2 hours prior to infection. A greater than 90% reduction in the yield of infectious virus was achieved at oligonucleotide concentrations of 10 to 20 micromolar. 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. PMID:24995383

  11. Neonatal herpes simplex virus.

    PubMed

    Berardi, Alberto; Lugli, Licia; Rossi, Cecilia; Maria, Chiara Laguardia; Guidotti, Isotta; Gallo, Claudio; Ferrari, Fabrizio

    2011-10-01

    Herpes simplex virus is an important cause of neonatal infection, which can lead to death or long-term disabilities. Rarely in utero, the transmission frequently occurs during delivery. The disease may be disseminated, localized to the central nervous system, or involving skin, eye and/or mouth. Mortality rates markedly decreased with high-dose antiviral treatment. Diagnosis of neonatal infection is based on viral isolation from ulcerated vesicles or by scarifying mucocutaneous lesions. Recently polymerase chain reaction plays a central role for both viral detection (skin, mucosal, cerebrospinal fluid samples) and response to therapy. Vertical transmission may be decreased by prophylactic antiviral treatment. PMID:21942600

  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. [Neonatal herpes simplex infection].

    PubMed

    van Ham-Borawitz, V E J; Stam, E D; Welborn, K M; Sas, T 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. PMID:27122069

  14. Evidence for antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication.

    PubMed Central

    Croen, K D

    1993-01-01

    Nitric oxide (NO) has antimicrobial activity against a wide spectrum of infectious pathogens, but an antiviral effect has not been reported. The impact of NO, from endogenous and exogenous sources, on herpes simplex virus type 1 (HSV 1) replication was studied in vitro. HSV 1 replication in RAW 264.7 macrophages was reduced 1,806-fold in monolayers induced to make NO by activation with gamma IFN and LPS. A competitive and a noncompetitive inhibitor of nitric oxide synthetase substantially reduced the antiviral effect of activated RAW macrophages. S-nitroso-L-acetyl penicillamine (SNAP) is a donor of NO and was added to the media of infected monolayers to assess the antiviral properties of NO in the absence of gamma IFN and LPS. A single dose of S-nitroso-L-acetyl penicillamine 3 h after infection inhibited HSV 1 replication in Vero, HEp2, and RAW 264.7 cells in a dose-dependent manner. Neither virucidal nor cytocidal effects of NO were observed under conditions that inhibited HSV 1 replication. Nitric oxide had inhibitory effects, comparable to that of gamma IFN/LPS, on protein and DNA synthesis as well as on cell replication. This report demonstrates that, among its diverse properties, NO has an antiviral effect. PMID:8390481

  15. Inhibition of cdk9 during Herpes Simplex Virus 1 Infection Impedes Viral Transcription

    PubMed Central

    Ou, Mark; Sandri-Goldin, Rozanne M.

    2013-01-01

    During herpes simplex virus 1 (HSV-1) infection there is a loss of the serine-2 phosphorylated form of RNA polymerase II (RNAP II) found in elongation complexes. This occurs in part because RNAP II undergoes ubiquitination and proteasomal degradation during times of highly active viral transcription, which may result from stalled elongating complexes. In addition, a viral protein, ICP22, was reported to trigger a loss of serine-2 RNAP II. These findings have led to some speculation that the serine-2 phosphorylated form of RNAP II may not be required for HSV-1 transcription, although this form is required for cellular transcription elongation and RNA processing. Cellular kinase cdk9 phosphorylates serine-2 in the C-terminal domain (CTD) of RNAP II. To determine if serine-2 phosphorylated RNAP II is required for HSV-1 transcription, we inhibited cdk9 during HSV-1 infection and measured viral gene expression. Inhibition was achieved by adding cdk9 inhibitors 5,6-dichlorobenzimidazone-1-β-D-ribofuranoside (DRB) or flavopiridol (FVP) or by expression of a dominant–negative cdk9 or HEXIM1, which in conjunction with 7SK snRNA inhibits cdk9 in complex with cyclin 1. Here we report that inhibition of cdk9 resulted in decreased viral yields and levels of late proteins, poor formation of viral transcription-replication compartments, reduced levels of poly(A)+ mRNA and decreased RNA synthesis as measured by uptake of 5-bromouridine into nascent RNA. Importantly, a global reduction in viral mRNAs was seen as determined by microarray analysis. We conclude that serine-2 phosphorylation of the CTD of RNAP II is required for HSV-1 transcription. PMID:24205359

  16. Herpes simplex keratitis.

    PubMed

    Kaye, Stephen; Choudhary, Anshoo

    2006-07-01

    Herpes simplex keratitis (HSK) results from an infection with the herpes simplex virus type 1 (HSV-1) also known as human herpesvirus type 1 (HHV-1). Primary infection may involve an ocular or non-ocular site, following which latency might be established principally in the trigeminal ganglion but also in the cornea. During latency, the virus appears as a circular episome associated with histones with active transcription only from the region encoding the latency-associated transcript (LAT). The LAT region is implicated in neuronal survival, anti-apoptosis, virulence, suppression of transcription, establishment of and reactivation from latency. The initial keratitis may develop after infection through the "front door route" (entry into the ocular surface from droplet spread) or "back door route" (spread to the eye from a non-ocular site, principally the mouth). The initial ocular infection may be mild. Visual morbidity results from recurrent keratitis, which leads to corneal scarring, thinning and neovascularisation. Although, recurrent disease may potentially occur through anterograde axonal spread from the trigeminal ganglion to the cornea, recent evidence suggests that HSV-1 in the cornea may be another source of recurrent disease. The pathogenesis and severity of HSK is largely determined by an interaction between viral genes encoded by the strain of HSV-1 and the make up of the host's immune system. Herpetic stromal disease is due to the immune response to virus within the cornea and the ability of the strain to cause corneal stromal disease is correlated with its ability to induce corneal vascularisation. The pathogenesis of corneal scarring and vascularisation is uncertain but appears to be a complex interaction of various cytokines, chemokines and growth factors either brought in by inflammatory cells or produced locally in response to HSV-1 infection. Evidence now suggests that HSV-1 infection disrupts the normal equilibrium between angiogenic and anti

  17. 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…

  18. 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 ...

  19. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

    SciTech Connect

    Zheng, Kai; Chen, Maoyun; Xiang, Yangfei; Ma, Kaiqi; Jin, Fujun; Wang, Xiao; Wang, Xiaoyan; Wang, Shaoxiang; Wang, Yifei

    2014-04-18

    Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.

  20. 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.

  1. Inhibition of Herpes Simplex Virus type 1 with the modified green tea polyphenol palmitoyl-epigallocatechin gallate

    PubMed Central

    de Oliveira, Aline; Adams, Sandra D.; Lee, Lee H.; Murray, Sean R.; Hsu, Stephen D.; Hammond, Jeffrey R.; Dickinson, Douglas; Chen, Ping; Chu, Tin-Chun

    2012-01-01

    Green tea polyphenol epigallocatechin gallate (EGCG) is a strong anti-oxidant that has previously been shown to reduce the number of plaques in HIV-infected cultured cells. Modified EGCG palmitoyl-EGCG (p-EGCG), is of interest as a topical antiviral agent for Herpes Simplex Virus (HSV-1) infections. This study evaluated the effect of p-EGCG on HSV-infected Vero cells. Results of cell viability and cell proliferation assays indicate that p-EGCG is not toxic to cultured Vero cells and show that modification of the green tea polyphenol epigallocatechin gallate (EGCG) with palmitate increases the effectiveness of EGCG as an antiviral agent. Furthermore, p-EGCG is a more potent inhibitor of Herpes Simplex Virus 1 (HSV-1) than EGCG and can be topically applied to skin, one of the primary tissues infected by HSV. Viral binding assay, plaque forming assay, PCR, real-time PCR, and fluorescence microscopy were used to demonstrate that p-EGCG concentrations of 50 µM and higher block the production of infectious HSV-1 particles. p-EGCG was found to inhibit HSV-1 adsorption to Vero cells. Thus, p-EGCG may provide a novel treatment for HSV-1 infections. PMID:23182741

  2. Zinc ionophores pyrithione inhibits herpes simplex virus replication through interfering with proteasome function and NF-κB activation.

    PubMed

    Qiu, Min; Chen, Yu; Chu, Ying; Song, Siwei; Yang, Na; Gao, Jie; Wu, Zhiwei

    2013-10-01

    Pyrithione (PT), known as a zinc ionophore, is effective against several pathogens from the Streptococcus and Staphylococcus genera. The antiviral activity of PT was also reported against a number of RNA viruses. In this paper, we showed that PT could effectively inhibit herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). PT inhibited HSV late gene (Glycoprotein D, gD) expression and the production of viral progeny, and this action was dependent on Zn(2+). Further studies showed that PT suppressed the expression of HSV immediate early (IE) gene, the infected cell polypeptide 4 (ICP4), but had less effect on another regulatory IE protein, ICP0. It was found that PT treatment could interfere with cellular ubiquitin-proteasome system (UPS), leading to the inhibition of HSV-2-induced IκB-α degradation to inhibit NF-κB activation and enhanced promyelocytic leukemia protein (PML) stability in nucleus. However, PT did not show direct inhibition of 26S proteasome activity. Instead, it induced Zn(2+) influx, which facilitated the dysregulation of UPS and the accumulation of intracellular ubiquitin-conjugates. UPS inhibition by PT caused disruption of IκB-α degradation and NF-κB activation thus leading to marked reduction of viral titer. PMID:23867132

  3. Hydroxyquinolines inhibit ribonucleic acid-dependent deoxyribonucleic acid polymerase and inactivate Rous sarcoma virus and herpes simplex virus.

    PubMed

    Rohde, W; Mikelens, P; Jackson, J; Blackman, J; Whitcher, J; Levinson, W

    1976-08-01

    8-Hydroxyquinoline and several of its derivatives inactivate the transforming ability of Rous sarcoma virus and inhibit its ribonucleic acid-dependent deoxyribonucleic acid polymerase activity. The copper complex of these metal-binding ligands is as active as the free ligand. The activity of the 8-hydroxyquinolines is approximately 50-fold more effective than another group of metal-binding compounds that we have tested, the thiosemicarbazones. In contrast to the potency of the 8-hydroxyquinolines to inactivate Rous sarcoma virus, no intracellular inhibition of transformation could be demonstrated at a concentration that did not affect the growth and appearance of the cells. Cellular deoxyribonucleic acid synthesis was inhibited to a greater extent than was ribonucleic acid or protein synthesis. The phenomenon of "concentration quenching" was observed with high concentrations of drug, causing less inhibition of deoxyribonucleic acid synthesis than was observed with lower concentrations. Herpes simplex virus type 1 was inactivated also by the 8-hydroxyquinolines and their copper complexes. No intracellular inhibition of plaque formation was observed. Treatment with 8-hydroxyquinoline sulfate had no effect on the resolution of herpetic keratitis in rabbits. Some 8-hydroxyquinolines bind to deoxyribonucleic acid in the presence of copper, a phenomenon that may be important in their antiviral activity. PMID:185949

  4. [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

  5. Medroxyprogesterone acetate inhibits CD8+ T cell viral specific effector function and induces herpes simplex virus type 1 reactivation

    PubMed Central

    Cherpes, Thomas L.; Busch, James L.; Sheridan, Brian S.; Harvey, Stephen A. K.; Hendricks, Robert L.

    2008-01-01

    Clinical research suggests hormonal contraceptive use is associated with increased frequencies of herpes simplex virus (HSV) reactivation and shedding. We examined the effects of medroxyprogesterone acetate (MPA), the compound most commonly used for injectable hormonal contraception, on HSV-1 reactivation and CD8+ T cell function in murine trigeminal ganglia (TG). In ex vivo TG cultures, MPA dramatically inhibited canonical CD8+ T cell effector functions, including IFN-γ production and lytic granule release, and increased HSV-1 reactivation from latency. In vivo, MPA treatment of latently infected ovariectomized mice inhibited IFN-γ production and lytic granule release by TG resident CD8+ T cells stimulated directly ex vivo. RNA specific for the essential immediate early viral gene ICP4 as well as viral genome DNA copy number were increased in mice that received MPA during latency, suggesting that treatment increased in vivo reactivation. The increase in HSV-1 copy number appeared to be the result of a two-tine effect, as MPA induced higher reactivation frequencies from latently infected explanted TG neurons in the presence or absence of CD45+ cells. Our data suggest hormonal contraceptives that contain MPA may promote increased frequency of HSV reactivation from latency through the combinatory effects of inhibiting protective CD8+ T cell responses and by a leukocyte-independent effect on infected neurons. PMID:18606648

  6. Inhibition of O-Linked N-Acetylglucosamine Transferase Reduces Replication of Herpes Simplex Virus and Human Cytomegalovirus

    PubMed Central

    Angelova, Magdalena; Ortiz-Meoz, Rodrigo F.; Walker, Suzanne

    2015-01-01

    ABSTRACT O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential cellular enzyme that posttranslationally modifies nuclear and cytoplasmic proteins via O-linked addition of a single N-acetylglucosamine (GlcNAc) moiety. Among the many targets of OGT is host cell factor 1 (HCF-1), a transcriptional regulator that is required for transactivation of the immediate-early genes of herpes simplex virus (HSV). HCF-1 is synthesized as a large precursor that is proteolytically cleaved by OGT, which may regulate its biological function. In this study, we tested whether inhibition of the enzymatic activity of OGT with a small molecule inhibitor, OSMI-1, affects initiation of HSV immediate-early gene expression and viral replication. We found that inhibiting OGT's enzymatic activity significantly decreased HSV replication. The major effect of the inhibitor occurred late in the viral replication cycle, when it reduced the levels of late proteins and inhibited capsid formation. However, depleting OGT levels with small interfering RNA (siRNA) reduced the expression of HSV immediate-early genes, in addition to reducing viral yields. In this study, we identified OGT as a novel cellular factor involved in HSV replication. Our results obtained using a small molecule inhibitor and siRNA depletion suggest that OGT's glycosylation and scaffolding functions play distinct roles in the replication cycle of HSV. IMPORTANCE Antiviral agents can target viral or host gene products essential for viral replication. O-GlcNAc transferase (OGT) is an important cellular enzyme that catalyzes the posttranslational addition of GlcNAc sugar residues to hundreds of nuclear and cytoplasmic proteins, and this modification regulates their activity and function. Some of the known OGT targets are cellular proteins that are critical for the expression of herpes simplex virus (HSV) genes, suggesting a role for OGT in the replication cycle of HSV. In this study, we found that OGT is required for

  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. Inhibition of herpes simplex virus 1 gene expression and replication by RNase P-associated external guide sequences.

    PubMed

    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

  9. Synthetic α-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses.

    PubMed

    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; Morrison, Lynda A

    2016-04-01

    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

  10. 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

  11. Inhibition of Herpes Simplex Virus gD and Lymphotoxin-α Binding to HveA by Peptide Antagonists

    PubMed Central

    Sarrias, Maria Rosa; Whitbeck, J. Charles; Rooney, Isabelle; Spruce, Lynn; Kay, Brian K.; Montgomery, Rebecca I.; Spear, Patricia G.; Ware, Carl F.; Eisenberg, Roselyn J.; Cohen, Gary H.; Lambris, John D.

    1999-01-01

    The herpesvirus entry mediator A (HveA) is a recently characterized member of the tumor necrosis factor receptor family that mediates the entry of most herpes simplex virus type 1 (HSV-1) strains into mammalian cells. Studies on the interaction of HSV-1 with HveA have shown that of all the viral proteins involved in uptake, only gD has been shown to bind directly to HveA, and this binding mediates viral entry into cells. In addition to gD binding to HveA, the latter has been shown to interact with proteins of tumor necrosis factor receptor-associated factor family, lymphotoxin-α (LT-α), and a membrane-associated protein referred to as LIGHT. To study the relationship between HveA, its natural ligands, and the viral proteins involved in HSV entry into cells, we have screened two phage-displayed combinatorial peptide libraries for peptide ligands of a recombinant form of HveA. Affinity selection experiments yielded two peptide ligands, BP-1 and BP-2, which could block the interaction between gD and HveA. Of the two peptides, only BP-2 inhibited HSV entry into CHO cells transfected with an HveA-expressing plasmid. When we analyzed these peptides for the ability to interfere with HveA binding to its natural ligand LT-α, we found that BP-1 inhibited the interaction of cellular LT-α with HveA. Thus, we have dissected the sites of interaction between the cell receptor, its natural ligand LT-α and gD, the virus-specific protein involved in HSV entry into cells. PMID:10364318

  12. 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

  13. Evidence for the Use of Multiple Mechanisms by Herpes Simplex Virus-1 R7020 to Inhibit Intimal Hyperplasia

    PubMed Central

    McCormick, Susan; He, Qi; Stern, Jordan; Khodarev, Nikolai; Weichselbaum, Ralph; Skelly, Christopher L.

    2015-01-01

    Intimal hyperplasia (IH) is the primary cause of vein bypass graft failure. The smooth muscle cell (SMC) is a key element of IH as it phenotypically switches from a contractile to a synthetic state which can become pathological. R7020, which is an engineered strain of Herpes Simplex Virus-1, inhibits IH in animal models. Although it has many characteristics which make it a strong candidate for use as a prophylactic agent how it inhibits IH is not well understood. The objective of this study was to identify modes of action used by R7020 to function in blood vessels that may also contribute to its inhibition of IH. The cytopathic effect of R7020 on SMCs was determined in vitro and in a rabbit IH model. In vitro assays with R7020 infected SMCs were used to quantify the effect of dose on the release kinetics of the virus as well as the effects of R7020 on cell viability and the adhesion of peripheral blood mononuclear cells (PBMCs) to SMCs in the absence and presence of tumor necrosis factor alpha (TNF-α). The observed cytopathic effect, which included R7020 positive filopodia that extend from cell to cell and the formation of syncytia, suggests that R7020 remains cell associated after egress and spreads cell to cell instead of by diffusion through the extracellular fluid. This would allow the virus to rapidly infect vascular cells while evading the immune system. The directionality of the filopodia in vivo suggests that the virus preferentially travels from the media towards the intima targeting SMCs that would lead to IH. The formation of syncytia would inhibit SMC proliferation as incorporated cells are not able to multiply. It was also observed that R7020 induced the fusion of PBMCs with syncytia suggesting the virus may limit the effect of macrophages on IH. Furthermore, R7020 inhibited the proliferative effect of TNF-α, an inflammatory cytokine associated with increased IH. Thus, the results of this study suggest that R7020 inhibits IH through multiple

  14. Recurrent lumbosacral herpes simplex virus infection

    PubMed Central

    Vassantachart, Janna M.

    2016-01-01

    We present the case of a 54-year-old white woman with episodic lumbosacral lesions that she had been treating as psoriasis. Evaluation revealed classic herpes simplex virus (HSV) infection. The discussion reviews the significance and potential complications of recurrent lumbosacral HSV infection. PMID:26722168

  15. 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

  16. 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

  17. 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…

  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. Aqueous extract from a Chaga medicinal mushroom, Inonotus obliquus (higher Basidiomycetes), prevents herpes simplex virus entry through inhibition of viral-induced membrane fusion.

    PubMed

    Pan, Hong-Hui; Yu, Xiong-Tao; Li, Ting; Wu, Hong-Ling; Jiao, Chun-Wei; Cai, Mian-Hua; Li, Xiang-Min; Xie, Yi-Zhen; Wang, Yi; Peng, Tao

    2013-01-01

    Chaga medicinal mushroom, Inonotus obliquus, a popular prescription in traditional medicine in Europe and Asia, was used to reduce inflammation in the nasopharynx and to facilitate breathing. The aqueous extract from I. obliquus (AEIO) exhibited marked decrease in herpes simplex virus (HSV) infection (the 50% inhibitory concentration was 3.82 μg/mL in the plaque reduction assay and 12.29 μg/mL in the HSV-1/blue assay) as well as safety in Vero cells (the 50% cellular cytotoxicity was > 1 mg/mL, and selection index was > 80). Using a time course assay, effective stage analysis, and fusion inhibition assay, the mechanism of anti-HSV activity was found against the early stage of viral infection through inhibition of viral-induced membrane fusion. Therefore, AEIO could effectively prevent HSV-1 entry by acting on viral glycoproteins, leading to the prevention of membrane fusion, which is different from nucleoside analog antiherpetics. PMID:23510282

  20. Herpes simplex virus colitis in a neonate.

    PubMed

    Daley, Andrew J; Craven, Paul; Holland, Andrew J A; Jones, Cheryl A; Badawi, Nadia; Isaacs, David

    2002-09-01

    Involvement of the gastrointestinal tract in neonates with congenital herpes simplex virus (HSV) infection is rarely described. We report a case of a newborn with disseminated HSV infection associated with profuse hematochezia and late sigmoid colon perforation. Histologic examination showed patchy areas of ulceration with multinucleated giant cells and HSV nucleic acid was detected by polymerase chain reaction in colonic tissue. No clinically apparent episodes of recurrent colitis occurred in the first year of life. PMID:12380594

  1. 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

  2. Inhibition of H3K27me3-Specific Histone Demethylases JMJD3 and UTX Blocks Reactivation of Herpes Simplex Virus 1 in Trigeminal Ganglion Neurons

    PubMed Central

    Messer, Harald G. P.; Jacobs, Derek; Dhummakupt, Adit

    2014-01-01

    Herpes simplex virus 1 (HSV-1) genomes are associated with the repressive heterochromatic marks H3K9me2/me3 and H3K27me3 during latency. Previous studies have demonstrated that inhibitors of H3K9me2/me3 histone demethylases reduce the ability of HSV-1 to reactivate from latency. Here we demonstrate that GSK-J4, a specific inhibitor of the H3K27me3 histone demethylases UTX and JMJD3, inhibits HSV-1 reactivation from sensory neurons in vitro. These results indicate that removal of the H3K27me3 mark plays a key role in HSV-1 reactivation. PMID:25552720

  3. Herpes simplex virus-1 infection causes the secretion of a type I interferon-antagonizing protein and inhibits signaling at or before Jak-1 activation

    SciTech Connect

    Johnson, Karen E.; Knipe, David M.

    2010-01-05

    Host cells respond to viral infection by the production of type I interferons (IFNs), which induce the expression of antiviral genes. Herpes simplex virus I (HSV-1) encodes many mechanisms that inhibit the type I IFN response, including the ICP27-dependent inhibition of type I IFN signaling. Here we show inhibition of Stat-1 nuclear accumulation in cells that express ICP27. ICP27 expression also induces the secretion of a small, heat-stable type I IFN antagonizing protein that inhibits Stat-1 nuclear accumulation. We show that the inhibition of IFN-induced Stat-1 phosphorylation occurs at or upstream of Jak-1 phosphorylation. Finally, we show that ISG15 expression is induced after IFNalpha treatment in mock-infected cells, but not cells infected with WT HSV-1 or ICP27{sup -} HSV-1. These data suggest that HSV-1 has evolved multiple mechanisms to inhibit IFN signaling not only in infected cells, but also in neighboring cells, thereby allowing for increased viral replication and spread.

  4. [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. PMID:23399415

  5. Herpes simplex encephalitis: adolescents and adults.

    PubMed

    Whitley, Richard J

    2006-09-01

    Herpes simplex encephalitis (HSE) remains one of the most devastating infections of the central nervous system despite available antiviral therapy. Children and adolescents account for approximately one third of all cases of HSE. Clinical diagnosis is suggested in the encephalopathic, febrile patient with focal neurologic signs. However, these clinical findings are not pathognomonic because numerous other diseases in the central nervous system can mimic HSE. Neurodiagnostic evaluation can provide support for the diagnosis by the demonstration of temporal lobe edema/hemorrhage by magnetic resonance image scan and spike and slow-wave activity on electroencephalogram. In the current era, the diagnostic gold standard is the detection of herpes simplex virus (HSV) DNA in the cerebrospinal fluid by polymerase chain reaction (PCR). Although PCR is an excellent test and preferable to brain biopsy, false negatives can occur early after disease onset. Acyclovir is the treatment of choice and is administered at 10 mg/kg every 8 h for 21 days. Even with early administration of therapy after the disease onset, nearly two thirds of survivors have significant residual neurologic deficits. Current investigative efforts are assessing the prognostic value of quantitative PCR detection of viral DNA at the onset of therapy as well as at the completion of therapy and the contribution of prolonged antiviral therapy to improved neurologic outcome. PMID:16675036

  6. Herpes simplex virus and the alimentary tract.

    PubMed

    Lavery, Eric A; Coyle, Walter J

    2008-08-01

    Herpes simplex virus (HSV) infection is well known as a sexually transmitted disease. However, relatively little has been published concerning the presentations and treatment of HSV infection within the gastrointestinal tract, where HSV most commonly affects the esophagus in both immunocompromised and immunocompetent patients. HSV proctitis is not uncommon and occurs primarily in males having sex with males. In patients with normal immune systems, gastrointestinal HSV infections are generally self-limited and rarely require antiviral therapy. Treatment of infection is suggested for immunocompromised patients, though no large randomized controlled trials have been performed. This article reviews the manifestations of HSV infection within the luminal gastrointestinal tract and options for diagnosis and treatment. PMID:18627656

  7. N-ethylmaleimide inhibition of the DNA-binding activity of the herpes simplex virus type 1 major DNA-binding protein

    SciTech Connect

    Ruyechan, W.T. )

    1988-03-01

    The major herpes simplex virus DNA-binding protein, designated ICP8, binds tightly to single-stranded DNA and is required for replication of viral DNA. The sensitivity of the DNA-binding activity of ICP8 to the action of the sulfhydryl reagent N-ethylmaleimide has been examined by using nitrocellulose filter-binding and agarose gel electrophoresis assays. Incubation of ICP8 with N-ethylmaleimide results in a rapid loss of DNA-binding activity. Preincubation of ICP8 with single-stranded DNA markedly inhibits this loss of binding activity. These results imply that a free sulfhydryl group is involved in the interaction of ICP8 with single-stranded DNA and that this sulfhydryl group becomes less accessible to the environment upon binding. Agarose gel electrophoretic analysis of the binding interaction in the presence and absence of N-ethylmaleimide indicates that the cooperative binding exhibited by ICP8 is lost upon treatment with this reagent but that some residual noncooperative binding may remain. This last result was confirmed by equilibrium dialysis experiments with the {sup 32}P-labeled oligonucleotide dT{sub 10} and native and N-ethylmaleimide-treated ICP8.

  8. Cytotoxicity in L929 fibroblasts and inhibition of herpes simplex virus type 1 Kupka by estuarine cyanobacteria extracts.

    PubMed

    Lopes, Viviana R; Schmidtke, Michaela; Helena Fernandes, M; Martins, Rosário; Vasconcelos, Vitor

    2011-06-01

    The cyanobacteria are known to be a rich source of metabolites with a variety of biological activities in different biological systems. In the present work, the bioactivity of aqueous and organic (methanolic and hexane) crude extracts of cyanobacteria isolated from estuarine ecosystems was studied using different bioassays. The assessment of DNA damage on the SOS gene repair region of mutant PQ37 strain of Escherichia coli was performed. Antiviral activity was evaluated against influenza virus, HRV-2, CVB3 and HSV-1 viruses using crystal violet dye uptake on HeLa, MDCK and GMK cell lines. Cytotoxicity evaluation was performed with L929 fibroblasts by MTT assay. Of a total of 18 cyanobacterial isolates studied, only the crude methanolic extract of LEGE 06078 proved to be genotoxic (IF > 1.5) in a dose-dependent manner and other four were putative candidates to induce DNA damage. Furthermore, the crude aqueous extract of LEGE 07085 showed anti- herpes type 1 activity (IC50 = 174.10 μg dry extract mL(-1)) while not presenting any cytotoxic activity against GMK cell lines. Of the 54 cyanobacterial extracts tested, only the crude methanolic and hexane ones showed impair on metabolic activity of L929 fibroblasts after long exposure (48-72 h). The inhibition of HSV-1 and the strong cytotoxicity against L929 cells observed emphasizes the importance of evaluating the impact of those estuarine cyanobacteria on aquatic ecosystem and on human health. The data also point out their potential application in HSV-1 treatment and pharmacological interest. PMID:21396440

  9. Antiviral agents for herpes simplex virus.

    PubMed

    Vere Hodge, R Anthony; Field, Hugh J

    2013-01-01

    This review starts with a brief description of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), the clinical diseases they cause, and the continuing clinical need for antiviral chemotherapy. A historical overview describes the progress from the early, rather toxic antivirals to acyclovir (ACV) which led the way for its prodrug, valacyclovir, to penciclovir and its prodrug, famciclovir (FCV). These compounds have been the mainstay of HSV therapy for two decades and have established a remarkable safety record. This review focuses on these compounds, the preclinical studies which reveal potentially important differences, the clinical trials, and the clinical experience through two decades. Some possible areas for further investigation are suggested. The focus shifts to new approaches and novel compounds, in particular, the combination of ACV with hydrocortisone, known as ME609 or zovirax duo, an HSV helicase-primase inhibitor, pritelivir (AIC316), and CMX001, the cidofovir prodrug for treating resistant HSV infection in immunocompromised patients. Letermovir has established that the human cytomegalovirus terminase enzyme is a valid target and that similar compounds could be sought for HSV. We discuss the difficulties facing the progression of new compounds. In our concluding remarks, we summarize the present situation including a discussion on the reclassification of FCV from prescription-only to pharmacist-controlled for herpes labialis in New Zealand in 2010; should this be repeated more widely? We conclude that HSV research is emerging from a quiescent phase. PMID:23885997

  10. In vitro inhibition of herpes simplex virus type 1 replication by Mentha suaveolens essential oil and its main component piperitenone oxide.

    PubMed

    Civitelli, Livia; Panella, Simona; Marcocci, Maria Elena; De Petris, Alberto; Garzoli, Stefania; Pepi, Federico; Vavala, Elisabetta; Ragno, Rino; Nencioni, Lucia; Palamara, Anna Teresa; Angiolella, Letizia

    2014-05-15

    Several essential oils exert in vitro activity against bacteria and viruses and, among these latter, herpes simplex virus type 1 (HSV-1) is known to develop resistance to commonly used antiviral agents. Thus, the effects of the essential oil derived from Mentha suaveolens (EOMS) and its active principle piperitenone oxide (PEO) were tested in in vitro experimental model of infection with HSV-1. The 50% inhibitory concentration (IC50) was determined at 5.1μg/ml and 1.4μg/ml for EOMS and PEO, respectively. Australian tea tree oil (TTO) was used as control, revealing an IC50 of 13.2μg/ml. Moreover, a synergistic action against HSV-1 was observed when each oil was added in combination with acyclovir. In order to find out the mechanism of action, EOMS, PEO and TTO were added to the cells at different times during the virus life-cycle. Results obtained by yield reduction assay indicated that the antiviral activity of both compounds was principally due to an effect after viral adsorption. Indeed, no reduction of virus yield was observed when cells were treated during viral adsorption or pre-treated before viral infection. In particular, PEO exerted a strong inhibitory effect by interfering with a late step of HSV-1 life-cycle. HSV-1 infection is known to induce a pro-oxidative state with depletion of the main intracellular antioxidant glutathione and this redox change in the cell is important for viral replication. Interestingly, the treatment with PEO corrected this deficit, thus suggesting that the compound could interfere with some redox-sensitive cellular pathways exploited for viral replication. Overall our data suggest that both EOMS and PEO could be considered good candidates for novel anti-HSV-1 strategies, and need further exploration to better characterize the targets underlying their inhibition. PMID:24629600

  11. Hydrolyzable Tannins (Chebulagic Acid and Punicalagin) Target Viral Glycoprotein-Glycosaminoglycan Interactions To Inhibit Herpes Simplex Virus 1 Entry and Cell-to-Cell Spread▿

    PubMed Central

    Lin, Liang-Tzung; Chen, Ting-Ying; Chung, Chueh-Yao; Noyce, Ryan S.; Grindley, T. Bruce; McCormick, Craig; Lin, Ta-Chen; Wang, Guey-Horng; Lin, Chun-Ching; Richardson, Christopher D.

    2011-01-01

    Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors that can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases of emerging acyclovir-resistant strains of herpesvirus. We report that chebulagic acid (CHLA) and punicalagin (PUG), two hydrolyzable tannins isolated from the dried fruits of Terminalia chebula Retz. (Combretaceae), inhibit HSV-1 entry at noncytotoxic doses in A549 human lung cells. Experiments revealed that both tannins targeted and inactivated HSV-1 viral particles and could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection. The antiviral effect from either of the tannins was not associated with induction of type I interferon-mediated responses, nor was pretreatment of the host cell protective against HSV-1. Their inhibitory activities targeted HSV-1 glycoproteins since both natural compounds were able to block polykaryocyte formation mediated by expression of recombinant viral glycoproteins involved in attachment and membrane fusion. Our results indicated that CHLA and PUG blocked interactions between cell surface glycosaminoglycans and HSV-1 glycoproteins. Furthermore, the antiviral activities from the two tannins were significantly diminished in mutant cell lines unable to produce heparan sulfate and chondroitin sulfate and could be rescued upon reconstitution of heparan sulfate biosynthesis. We suggest that the hydrolyzable tannins CHLA and PUG may be useful as competitors for glycosaminoglycans in the management of HSV-1 infections and that they may help reduce the risk for development of viral drug resistance during therapy with nucleoside analogues. PMID:21307190

  12. Downregulation of Cellular c-Jun N-Terminal Protein Kinase and NF-κB Activation by Berberine May Result in Inhibition of Herpes Simplex Virus Replication

    PubMed Central

    Song, Siwei; Qiu, Min; Chu, Ying; Chen, Deyan; Wang, Xiaohui; Su, Airong

    2014-01-01

    Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. Some reports show that berberine exhibits anti-inflammatory, antitumor, and antiviral properties by modulating multiple cellular signaling pathways, including p53, nuclear factor κB (NF-κB), and mitogen-activated protein kinase. In the present study, we investigated the antiviral effect of berberine against herpes simplex virus (HSV) infection. Current antiherpes medicines such as acyclovir can lessen the recurring activation when used early at infection but are unable to prevent or cure infections where treatment has selected for resistant mutants. In searching for new antiviral agents against herpesvirus infection, we found that berberine reduced viral RNA transcription, protein synthesis, and virus titers in a dose-dependent manner. To elucidate the mechanism of its antiviral activity, the effect of berberine on the individual steps of viral replication cycle of HSV was investigated via time-of-drug addition assay. We found that berberine acted at the early stage of HSV replication cycle, between viral attachment/entry and genomic DNA replication, probably at the immediate-early gene expression stage. We further demonstrated that berberine significantly reduced HSV-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. Moreover, we found that berberine also depressed HSV-induced c-Jun N-terminal kinase (JNK) phosphorylation but had little effect on p38 phosphorylation. Our results suggest that the berberine inhibition of HSV infection may be mediated through modulating cellular JNK and NF-κB pathways. PMID:24913175

  13. Vaccines for herpes simplex virus infections.

    PubMed

    Koelle, David M

    2006-02-01

    Infections with herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2) can have serious medical consequences. Although antiviral medications can suppress symptomatic disease, asymptomatic shedding and transmission, they neither cure nor alter the natural history of HSV infections. Manipulation of the immune response is one potential method to decrease disease burden. Current research on prophylactic and therapeutic vaccination approaches is discussed in this review, with a focus on compounds that have entered clinical trials or that display novel compositions or proposed mechanisms of action. One such vaccine is an alum and monophosphoryl lipid A-adjuvanted subunit glycoprotein D2 vaccine that has demonstrated activity in the prevention of HSV-2 infection and disease in HSV-uninfected women in a phase III clinical trial. Further confirmatory clinical trials of this vaccine are currently underway. Other vaccine formats also in development include attenuated live or replication-incompetent HSV-2 strains and technologies that target virus-specific CD8 T-cell responses. PMID:16499283

  14. Herpes simplex virus duodenitis accompanying Crohn's disease.

    PubMed

    Lee, Byung Hoo; Um, Wook Hyun; Jeon, Seong Ran; Kim, Hyun Gun; Lee, Tae Hee; Kim, Wan Jung; Kim, Jin-Oh; Jin, So Young

    2013-11-01

    Herpes simplex virus (HSV) is a recognized cause of gastrointestinal infection in immunodeficient patients. Although a few cases of HSV gastritis and colitis in immunocompromised patients have been reported, there are no reports of HSV duodenitis in patients with Crohn's disease (CD). A 74-year-old female was admitted with general weakness and refractory epigastric pain. She had been diagnosed with CD three years ago. Esophagogastroduodenoscopy (EGD) revealed diffuse edematous and whitish mucosa with multiple erosions in the duodenum. Considering the possibility of viral co-infection, cytomegalovirus (CMV) immunohistochemical staining, PCR, and cultures of duodenal biopsies were performed, all of which were negative with the exception of the isolation of HSV in culture. After administration of intravenous acyclovir for 1 week, follow-up EGD showed almost complete resolution of the lesions and the patient's symptoms improved. In CD patients with refractory gastro-intestinal symptoms, HSV, as well as CMV, should be considered as a possible cause of infection, so that the diagnosis of viral infection is not delayed and the appropriate antiviral treatment can be initiated. PMID:24262595

  15. Uncoating the Herpes Simplex Virus Genome

    PubMed Central

    Newcomb, William W.; Brown, Jay C.

    2007-01-01

    Summary Initiation of infection by herpes simplex virus (HSV-1) involves a step in which the parental virus capsid docks at a nuclear pore and injects its DNA into the nucleus. Once “uncoated” in this way, the virus DNA can be transcribed and replicated. In an effort to clarify the mechanism of DNA injection, we examined DNA release as it occurs in purified capsids incubated in vitro. DNA ejection was observed following two different treatments, trypsin digestion of capsids in solution, and heating of capsids after attachment to a solid surface. In both cases, electron microscopic analysis revealed that DNA was ejected as a single double helix with ejection occurring at one vertex presumed to be the portal. In the case of trypsin-treated capsids, DNA release was found to correlate with cleavage of a small proportion of the portal protein, UL6, suggesting UL6 cleavage may be involved in making the capsid permissive for DNA ejection. In capsids bound to a solid surface, DNA ejection was observed only when capsids were warmed above 4°C. The proportion of capsids releasing their DNA increased as a function of incubation temperature with nearly all capsids ejecting their DNA when incubation was at 37°C. The results demonstrate heterogeneity among HSV-1 capsids with respect to their sensitivity to heat-induced DNA ejection. Such heterogeneity may indicate a similar heterogeneity in the ease with which capsids are able to deliver DNA to the infected cell nucleus. PMID:17540405

  16. 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

  17. Effects of herpes simplex virus on mRNA stability.

    PubMed Central

    Strom, T; Frenkel, N

    1987-01-01

    Herpes simplex virus virions contain one or more functions which mediate shutoff of host protein synthesis, disaggregation of host polyribosomes, and degradation of host mRNA. We studied aspects of the host shutoff mechanism by using herpes simplex virus type 1 mutants deficient in virion-induced shutoff of host protein synthesis (G. S. Read and N. Frenkel, J. Virol. 46:498-512, 1983). Shutoff of host protein synthesis by the wild-type virus was associated with degradation of host mRNAs, including beta-actin, alpha-tubulin, and heat shock protein 70. In contrast, the virion host shutoff (vhs) mutants were deficient to various degrees in their ability to induce host mRNA degradation; the extent of mRNA degradation correlated well with the extent of inhibition of host protein synthesis. This finding suggests that inhibition of host protein synthesis and degradation of host mRNA were mediated by the same virion-associated function. Virion-induced degradation of host mRNA was not prevented by inhibitors of ribosome translocation, nor could it be augmented, for mutant vhs-1, by drugs which disaggregate polyribosomes. This suggests that mRNA in polyribosomes, as well as nonpolyribosomal mRNA, is susceptible to virion-induced degradation. Finally, the half-life of viral transcripts was also prolonged in cells infected with the vhs-1 mutant virus, suggesting that the vhs function indiscriminately decreased the half-lives of both host and viral mRNAs. The vhs function may thus play a dual role in virus infection. (i) It inhibits host gene expression, and (ii) it enables rapid transitions in the expression of viral genes which are sequentially transcribed as infection progresses. Images PMID:3035220

  18. 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

  19. 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

  20. [The lysate and recombinant antigens in ELISA-test-systems for diagnostic of herpes simplex].

    PubMed

    Ganova, L A; Kovtoniuk, G V; Korshun, L N; Kiseleva, E K; Tereshchenko, M I; Vudmaska, M I; Moĭsa, L N; Shevchuk, V A; Spivak, N Ia

    2014-08-01

    The lysate and recombinant antigens of various production included informula of ELISA-test-systems were analyzed. The ELISA-test-systems are used for detection of IgG to Herpes simplex virus type I and II. For testing the panel of serums PTH 201 (BBI Inc.) were used. The samples of this panel contain antibodies to Herpes simplex virus type I and II in mixed titers. The 69 serums of donors were used too (17 samples had IgG to Herpes simplex virus type I, 23 samples to Herpes simplex virus type II and 29 samples had no antibodies to Herpes simplex virus). The diagnostic capacity of mixture of recombinant antigens gG1 Herpes simplex virus type I and gG2 Herpes simplex virus type II (The research-and-production complex "DiaprofMed") was comparable with mixture of lysate antigen Herpes simplex virus type I and II (Membrane) EIE Antigen ("Virion Ltd."). In the test-systems for differentiation of IgG to Herpes simplex virus type I the recombinant antigen gG1 Herpes simplex virus type I proved to be comparable with commercial analogue Herpes simplex virus-1 gG1M ("Viral Therapeutics Inc."'). At the same time, capacity to detect IgG to Herpes simplex virus type II in recombinant protein gG2 Herpes simplex virus type II is significantly higher than in its analogue Herpes simplex virus-2 gG2c ("Viral Therapeutics Inc."). PMID:25552056

  1. 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)

  2. 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)

  3. 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

  4. Intrauterine herpes simplex virus infection presenting with hypopigmented lesions.

    PubMed

    Low, Lynette C M; Carton, James; Walker, Marjorie; Tudor-Williams, Gareth; Hardman, Catherine

    2012-01-01

    Genital herpes simplex virus (HSV) is a sexually transmitted infection that can be transmitted from mother to child in utero, perinatally, or postnatally. Cutaneous infection with HSV commonly presents as vesicles affecting the skin, eyes, or mouth. In our case, we report a well child with cutaneous hypopigmented patches at birth that preceded typical blistering. PMID:22010816

  5. Recurrent Lymphocytic Meningitis Positive for Herpes Simplex Virus Type 2

    PubMed Central

    Seppänen, Mikko; Kautiainen, Hannu; Lokki, Marja-Liisa; Lappalainen, Maija; Valtonen, Ville; Färkkilä, Markus; Kalso, Eija

    2009-01-01

    We found the prevalence of recurrent lymphocytic meningitis associated with herpes simplex virus type 2 (HSV-2) was 2.2/100,000 population in Finland during 1996–2006, higher than previous estimates. PCR was most sensitive in detecting HSV-2 DNA from cerebrospinal fluid if the sample was taken 2–5 days after symptom onset. PMID:19624935

  6. Recurrent lymphocytic meningitis positive for herpes simplex virus type 2.

    PubMed

    Kallio-Laine, Katariina; Seppänen, Mikko; Kautiainen, Hannu; Lokki, Marja Liisa; Lappalainen, Maija; Valtonen, Ville; Färkkilä, Markus; Kalso, Eija

    2009-07-01

    We found the prevalence of recurrent lymphocytic meningitis associated with herpes simplex virus type 2 (HSV-2) was 2.2/100,000 population in Finland during 1996-2006, higher than previous estimates. PCR was most sensitive in detecting HSV-2 DNA from cerebrospinal fluid if the sample was taken 2-5 days after symptom onset. PMID:19624935

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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. PMID:25341185

  13. 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

  14. Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host-cell interaction

    NASA Astrophysics Data System (ADS)

    Hu, Yu-Peng; Lin, Shu-Yi; Huang, Cheng-Yen; Zulueta, Medel Manuel L.; Liu, Jing-Yuan; Chang, Wen; Hung, Shang-Cheng

    2011-07-01

    Cell surface carbohydrates play significant roles in a number of biologically important processes. Heparan sulfate, for instance, is a ubiquitously distributed polysulfated polysaccharide that is involved, among other things, in the initial step of herpes simplex virus type 1 (HSV-1) infection. The virus interacts with cell-surface heparan sulfate to facilitate host-cell attachment and entry. 3-O-Sulfonated heparan sulfate has been found to function as an HSV-1 entry receptor. Achieving a complete understanding of these interactions requires the chemical synthesis of such oligosaccharides, but this remains challenging. Here, we present a convenient approach for the synthesis of two irregular 3-O-sulfonated heparan sulfate octasaccharides, making use of a key disaccharide intermediate to acquire different building blocks for the oligosaccharide chain assembly. Despite substantial structural differences, the prepared 3-O-sulfonated sugars blocked viral infection in a dosage-dependent manner with remarkable similarity to one another.

  15. Autism and Herpes Simplex Encephalitis. Brief Report.

    ERIC Educational Resources Information Center

    Ghaziuddin, Mohammad; And Others

    1992-01-01

    This paper presents two case studies of children who developed herpes virus infection in the intrauterine or early postnatal period and presented with features of autism around two years of age. Other research suggesting a link between herpes and autism is reviewed. (DB)

  16. Regulation of viral gene expression by the herpes simplex virus 1UL24 protein (HSV-1UL24 inhibits accumulation of viral transcripts).

    PubMed

    Sanabria-Solano, Carolina; Gonzalez, Carmen Elena; Richerioux, Nicolas; Bertrand, Luc; Dridi, Slimane; Griffiths, Anthony; Langelier, Yves; Pearson, Angela

    2016-08-01

    UL24 is conserved among all Herpesviridae. In herpes simplex virus 1 (HSV-1), UL24 mutations lead to reduced viral titers both in cell culture and in vivo, and reduced pathogenicity. The human cytomegalovirus ortholog of UL24 has a gene regulatory function; however, it is not known whether other UL24 orthologs also affect gene expression. We discovered that in co-transfection experiments, expression of UL24 correlated with a reduction in the expression of several viral proteins and transcripts. Substitution mutations targeting conserved residues in UL24 impaired this function. Reduced transcript levels did not appear attributable to changes in mRNA stability. The UL24 ortholog of Herpes B virus exhibited a similar activity. An HSV-1 mutant that does not express UL24 produced more viral R1 and R2 transcripts than the wild type or rescue virus relative to the amount of viral DNA. These results reveal a new role for HSV-1UL24 in regulating viral mRNA accumulation. PMID:27214229

  17. Fatal Neonatal Herpes Simplex Infection Likely from Unrecognized Breast Lesions.

    PubMed

    Field, Scott S

    2016-02-01

    Type 1 herpes simplex virus (HSV-1) is very prevalent yet in rare circumstances can lead to fatal neonatal disease. Genital acquisition of type 2 HSV is the usual mode for neonatal herpes, but HSV-1 transmission by genital or extragenital means may result in greater mortality rates. A very rare scenario is presented in which the mode of transmission was likely through breast lesions. The lesions were seen by nurses as well as the lactation consultant and obstetrician in the hospital after delivery of the affected baby but not recognized as possibly being caused by herpes. The baby died 9 days after birth with hepatic failure and disseminated intravascular coagulation. Peripartum health care workers need to be aware of potential nongenital (including from the breast[s]) neonatal herpes acquisition, which can be lethal. PMID:26185119

  18. Antiviral activity of sandalwood oil against herpes simplex viruses-1 and -2.

    PubMed

    Benencia, F; Courrèges, M C

    1999-05-01

    Sandalwood oil, the essential oil of Santalum album L., was tested for in vitro antiviral activity against Herpes simplex viruses-1 and -2. It was found that the replication of these viruses was inhibited in the presence of the oil. This effect was dose-dependent and more pronounced against HSV-1. A slight diminution of the effect was observed at higher multiplicity of infections. The oil was not virucidal and showed no cytotoxicity at the concentrations tested. PMID:10374251

  19. 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

  20. Herpes simplex encephalitis in a domestic rabbit (Oryctolagus cuniculus).

    PubMed

    Grest, P; Albicker, P; Hoelzle, L; Wild, P; Pospischil, A

    2002-05-01

    An adult domestic rabbit showing neurological signs was subjected to euthanasia. At necropsy, macroscopical lesions were absent. Histopathologically, extensive lesions were seen, particularly in the cerebral cortex. Non-suppurative meningitis was present and there was lymphocytic and plasmacytic perivascular cuffing in the neuropil. The cerebral cortex showed extensive segmental neuronal and glial necrosis. Within the necrotic areas, large amphophilic intranuclear inclusion bodies were present in neurons and glial cells. Immunohistochemically, neurons and glial cells in the affected areas were labelled by polyclonal antibodies against both herpes simplex virus-1 (HSV-1) and HSV-2. The agent was classified as HSV-1 by polymerase chain reaction analysis. This is only the second reported natural case of herpes simplex infection in a rabbit. PMID:12056779

  1. 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.

  2. 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

  3. Herpes simplex virus induces the replication of foreign DNA.

    PubMed Central

    Danovich, R M; Frenkel, N

    1988-01-01

    Plasmids containing the simian virus 40 (SV40) DNA replication origin and the large T gene are replicated efficiently in Vero monkey cells but not in rabbit skin cells. Efficient replication of the plasmids was observed in rabbit skin cells infected with herpes simplex virus type 1 (HSV-1) and HSV-2. The HSV-induced replication required the large T antigen and the SV40 replication origin. However, it produced concatemeric molecules resembling replicative intermediates of HSV DNA and was sensitive to phosphonoacetate at concentrations known to inhibit the HSV DNA polymerase. Therefore, it involved the HSV DNA polymerase itself or a viral gene product(s) which was expressed following the replication of HSV DNA. Analyses of test plasmids lacking SV40 or HSV DNA sequences showed that, under some conditions, HSV also induced low-level replication of test plasmids containing no known eucaryotic replication origins. Together, these results show that HSV induces a DNA replicative activity which amplifies foreign DNA. The relevance of these findings to the putative transforming potential of HSV is discussed. Images PMID:2850486

  4. Herpes simplex virus induces the replication of foreign DNA

    SciTech Connect

    Danovich, R.M.; Frenkel, N.

    1988-08-01

    Plasmids containing the simian virus 40 (SV40) DNA replication origin and the large T gene are replicated in Vero monkey cells but not in rabbit skin cells. Efficient replication of the plasmids was observed in rabbit cells infected with herpes simplex virus type 1 (HSV-1) and HSV-2. The HSV-induced replication required the large T antigen and the SV40 replication origin. However, it produced concatemeric molecules resembling replicative intermediates of HSV DNA and was sensitive to phosphonoacetate at concentrations known to inhibit the HSV DNA polymerase. Therefore, it involved the HSV DNA polymerase itself or a viral gene product(s) which was expressed following the replication of HSV DNA. Analyses of test plasmids lacking SV40 or HSV DNA sequences showed that, under some conditions. HSV also induced low-level replication of test plasmids containing no known eucaryotic replication origins. Together, these results show that HSV induces a DNA replicative activity which amplifies foreign DNA. The relevance of these findings to the putative transforming potential of HSV is discussed.

  5. 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.

  6. Herpes simplex viruses lacking glycoprotein D are unable to inhibit virus penetration: quantitative evidence for virus-specific cell surface receptors

    SciTech Connect

    Johnson, D.C.; Ligas, M.W.

    1988-12-01

    Herpes simplex virus (HSV) glycoprotein D (gD) plays an essential role in the entry of virus into cells. HSV mutants unable to express gD were constructed. The mutants can be propagated on VD60 cells, which supply the viruses with gD; however, virus particles lacking gD were produced in mutant-infected Vero cells. Virus particles with or without gD adsorbed to a large number of sites on the cell surface; however, virions lacking gD did not enter cells. Cells pretreated with UV-inactivated virions containing gD were resistant to infection with HSV type 1 (HSV-1) and HSV-2. In contrast, cell pretreated with UV-inactivated virions lacking gD could be infected with HSV-1 and HSV-2. If infectious HSV-1 was added prior to UV-inactivated virus particles containing gD, the infectious virus entered cells and replicated. Therefore, virus particles containing gD appear to block specific cell surface receptors which are very limited in number. Particles lacking gD are presumably unable to interact with these receptors, suggesting that gD is an essential receptor-binding polypeptide.

  7. Evolutionary Origins of Human Herpes Simplex Viruses 1 and 2

    PubMed Central

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

    2014-01-01

    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. PMID:24916030

  8. 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

  9. Herpes simplex virus latency in isolated human neurons.

    PubMed Central

    Wigdahl, B; Smith, C A; Traglia, H M; Rapp, F

    1984-01-01

    Herpes simplex virus is most probably maintained in the ganglion neurons of the peripheral nervous system of humans in a latent form that can reactivate to produce recurrent disease. As an approximation of this cell-virus interaction, we have constructed a herpes simplex virus latency in vitro model system using human fetus sensory neurons as the host cell. Human fetus neurons were characterized as neuronal in origin by the detection of the neuropeptide substance P and the neuron-specific plasma membrane A2B5 antigen. Virus latency was established by blocking complete expression of the virus genome by treatment of infected human neurons with a combination of human leukocyte interferon and (E)-5-(2-bromovinyl)-2'-deoxyuridine for 7 days. After removal of inhibitors, virus latency was maintained for at least 9 days. This in vitro model will provide a system to analyze, in a primary human neuron, the state of the herpes simplex virus genome during establishment and maintenance of experimental latency. Images PMID:6091142

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

    PubMed Central

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

    1981-01-01

    Herpes simplex virus type 1 is photosensitized by treatment with fluorescein isothiocyante (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 micrograms/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 micrograms/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. Images PMID:6262783

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

    PubMed

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

    1981-02-01

    Herpes simplex virus type 1 is photosensitized by treatment with fluorescein isothiocyante (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 micrograms/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 micrograms/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. PMID:6262783

  12. 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.

  13. Herpes simplex virus latency-associated transcript is a stable intron.

    PubMed Central

    Farrell, M J; Dobson, A T; Feldman, L T

    1991-01-01

    The latency-associated transcript (LAT) is the major viral transcript detected by in situ hybridization of mouse and human sensory ganglia latently infected with herpes simplex virus type 1. The last 750 bases of LAT are complementary to infected-cell polypeptide 0, a herpes simplex virus type 1 immediate-early gene that encodes a transactivating protein that may facilitate re-activation of the virus from the latent state. Several laboratories have shown that LAT accumulates in the nucleus and is not polyadenylylated. Recently, we showed that the promoter for LAT lies 688 bases upstream from its 5' end. We report here that LAT is actually a uniquely stable intron. Furthermore, LAT effectively inhibits transactivation of gene expression by infected-cell polypeptide 0 in transient transfection assays. Images PMID:1846963

  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. PMID:19023806

  15. Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro.

    PubMed

    Schuhmacher, A; Reichling, J; Schnitzler, P

    2003-01-01

    The virucidal effect of peppermint oil, the essential oil of Mentha piperita, against herpes simplex virus was examined. The inhibitory activity against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) was tested in vitro on RC-37 cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of peppermint oil for herpes simplex virus plaque formation was determined at 0.002% and 0.0008% for HSV-1 and HSV-2, respectively. Peppermint oil exhibited high levels of virucidal activity against HSV-1 and HSV-2 in viral suspension tests. At noncytotoxic concentrations of the oil, plaque formation was significantly reduced by 82% and 92% for HSV-1 and HSV-2, respectively. Higher concentrations of peppermint oil reduced viral titers of both herpesviruses by more than 90%. A clearly time-dependent activity could be demonstrated, after 3 h of incubation of herpes simplex virus with peppermint oil an antiviral activity of about 99% could be demonstrated. In order to determine the mode of antiviral action of the essential oil, peppermint oil was added at different times to the cells or viruses during infection. Both herpesviruses were significantly inhibited when herpes simplex virus was pretreated with the essential oil prior to adsorption. These results indicate that peppermint oil affected the virus before adsorption, but not after penetration into the host cell. Thus this essential oil is capable to exert a direct virucidal effect on HSV. Peppermint oil is also active against an acyclovir resistant strain of HSV-1 (HSV-1-ACV(res)), plaque formation was significantly reduced by 99%. Considering the lipophilic nature of the oil which enables it to penetrate the skin, peppermint oil might be suitable for topical therapeutic use as virucidal agent in recurrent herpes infection. PMID:13678235

  16. Immunity to herpes simplex virus type 2. Suppression of virus-induced immune responses in ultraviolet B-irradiated mice

    SciTech Connect

    Yasumoto, S.; Hayashi, Y.; Aurelian, L.

    1987-10-15

    Ultraviolet B irradiation (280 to 320 nm) of mice at the site of intradermal infection with herpes simplex virus type 2 increased the severity of the herpes simplex virus type 2 disease and decreased delayed-type hypersensitivity (DTH) responses to viral antigen. Decrease in DTH resulted from the induction of suppressor T cells, as evidenced by the ability of spleen cells from UV-irradiated mice to inhibit DTH and proliferative responses after adoptive transfer. Lymph node cells from UV-irradiated animals did not transfer suppression. DTH was suppressed at the induction but not the expression phase. Suppressor T cells were Lyt-1+, L3T4+, and their activity was antigen-specific. However, after in vitro culture of spleen cells from UV-irradiated mice with herpes simplex virus type 2 antigen, suppressor activity was mediated by Lyt-2+ cells. Culture supernatants contained soluble nonantigen-specific suppressive factors.

  17. Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research

    PubMed Central

    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

  18. 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

  19. Herpes simplex virus 2 infection impacts stress granule accumulation.

    PubMed

    Finnen, Renée L; Pangka, Kyle R; Banfield, Bruce W

    2012-08-01

    Interference with stress granule (SG) accumulation is gaining increased appreciation as a common strategy used by diverse viruses to facilitate their replication and to cope with translational arrest. Here, we examined the impact of infection by herpes simplex virus 2 (HSV-2) on SG accumulation by monitoring the localization of the SG components T cell internal antigen 1 (TIA-1), Ras-GTPase-activating SH3-domain-binding protein (G3BP), and poly(A)-binding protein (PABP). Our results indicate that SGs do not accumulate in HSV-2-infected cells and that HSV-2 can interfere with arsenite-induced SG accumulation early after infection. Surprisingly, SG accumulation was inhibited despite increased phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), implying that HSV-2 encodes previously unrecognized activities designed to maintain translation initiation downstream of eIF2α. SG accumulation was not inhibited in HSV-2-infected cells treated with pateamine A, an inducer that works independently of eIF2α phosphorylation. The SGs that accumulated following pateamine A treatment of infected cells contained G3BP and PABP but were largely devoid of TIA-1. We also identified novel nuclear structures containing TIA-1 that form late in infection. These structures contain the RNA binding protein 68-kDa Src-associated in mitosis (Sam68) and were noticeably absent in infected cells treated with inhibitors of viral DNA replication, suggesting that they arise as a result of late events in the virus replicative cycle. PMID:22623775

  20. Antiviral activity of 1-docosanol, an inhibitor of lipid-enveloped viruses including herpes simplex.

    PubMed Central

    Katz, D H; Marcelletti, J F; Khalil, M H; Pope, L E; Katz, L R

    1991-01-01

    This article reports that 1-docosanol, a 22-carbon-long saturated alcohol, exerts a substantial inhibitory effect on replication of certain viruses (e.g., herpes simplex virus and respiratory syncytial virus) within primary target cells in vitro. To study the basis for its viral inhibitory activity, a suspension of 1-docosanol was formulated in an inert and nontoxic surfactant, Pluronic F-68; this suspension exerted potent inhibitory activity on the ability of susceptible viruses to infect cultured target cells. Susceptible viruses included wild-type herpes simplex viruses 1 and 2 as well as acyclovir-resistant herpes simplex virus 2 and also respiratory syncytial virus--all of which are lipid-enveloped. In contrast, nonenveloped poliovirus was not susceptible to the inhibitory action of 1-docosanol. Although the precise mechanism has yet to be defined, current evidence suggests that 1-docosanol inhibits viral replication by interfering with the early intracellular events surrounding viral entry into target cells. It is possible that interaction between the highly lipophilic compound and components of target cell membranes renders such target cells less susceptible to viral fusion and/or entry. If this mechanism proves to be correct, 1-docosanol may provide a broad spectrum activity against many different viruses, especially those with lipid-containing envelopes. Images PMID:1660151

  1. [Role of herpes simplex virus in the development of exudative erythema multiforme].

    PubMed

    Samgin, M A; Ivanov, O L; Kuzheleva, S A; Biriukov, A V; L'vov, N D

    1990-03-01

    The paper presents analysis of current knowledge on etiology and immunopathogenesis of multiform exudative erythema (MEE). Among a variety of pathogenetic actions of herpes simplex on immune system are those relevant to MEE onset. These variants are dealt with in detail. The view on MEE as resultant from herpes simplex infection promises appearance of new prospective modes of etiotropic therapy. PMID:2370760

  2. 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

  3. Herpes Simplex Virus-2 Esophagitis in a Young Immunocompetent Adult

    PubMed Central

    Kadayakkara, Deepak K.; Candelaria, Angela; Kwak, Ye Eun; Loeser, Caroline

    2016-01-01

    Herpes simplex esophagitis (HSE) is commonly identified in immunosuppressed patients. It is rare among immunocompetent patients and almost all of the reported cases are due to HSV-1 infection. HSV-2 esophagitis is extremely rare. We report the case of a young immunocompetent male who presented with dysphagia, odynophagia, and epigastric pain. Endoscopy showed multitudes of white nummular lesions in the distal esophagus initially suspected to be candida esophagitis. However, classic histopathological findings of multinucleated giant cells with eosinophilic intranuclear inclusions and positive HSV-2 IgM confirmed the diagnosis of HSV-2 esophagitis. The patient rapidly responded to acyclovir treatment. Although HSV-2 is predominantly associated with genital herpes, it can cause infections in other parts of the body previously attributed to only HSV-1 infection. PMID:27195158

  4. Autophagy Stimulation Abrogates Herpes simplex Virus-1 Infection

    PubMed Central

    Yakoub, Abraam M.; Shukla, Deepak

    2015-01-01

    Herpes simplex virus-1 (HSV-1) is a double-stranded DNA virus that causes life-long infections. HSV-1 infections may lead to herpetic stromal keratitis that may advance to corneal blindness. HSV-1 infections can also cause fatal conditions, such as herpes encephalitis, or neonatal disease. A major virulence mechanism of HSV-1 is the control of autophagy, an innate immune defense strategy that could otherwise degrade viral particles. Here, to investigate a new mechanism for antiviral therapy, we tested the effect of various autophagy inducers (physiological and pharmacological) on infection. Autophagy stimulation was confirmed to significantly suppress HSV-1 infection in various cell types, without affecting cell viability. This study establishes the importance of autophagy for regulating HSV-1 infection, and provides a proof-of-principle evidence for a novel antiviral mechanism. PMID:25856282

  5. Herpes Simplex Virus-2 Esophagitis in a Young Immunocompetent Adult.

    PubMed

    Kadayakkara, Deepak K; Candelaria, Angela; Kwak, Ye Eun; Loeser, Caroline

    2016-01-01

    Herpes simplex esophagitis (HSE) is commonly identified in immunosuppressed patients. It is rare among immunocompetent patients and almost all of the reported cases are due to HSV-1 infection. HSV-2 esophagitis is extremely rare. We report the case of a young immunocompetent male who presented with dysphagia, odynophagia, and epigastric pain. Endoscopy showed multitudes of white nummular lesions in the distal esophagus initially suspected to be candida esophagitis. However, classic histopathological findings of multinucleated giant cells with eosinophilic intranuclear inclusions and positive HSV-2 IgM confirmed the diagnosis of HSV-2 esophagitis. The patient rapidly responded to acyclovir treatment. Although HSV-2 is predominantly associated with genital herpes, it can cause infections in other parts of the body previously attributed to only HSV-1 infection. PMID:27195158

  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. Herpes simplex virus hepatitis 4 years after liver transplantation.

    PubMed

    Bissig, Karl-Dimiter; Zimmermann, Arthur; Bernasch, Dirke; Furrer, Hansjakob; Dufour, Jean-FranCois

    2003-01-01

    If not promptly recognized and treated, herpes simplex virus (HSV) hepatitis is associated with a high mortality. A patient transplanted for primary sclerosing cholangitis required, 4 years later, a colectomy for a steroid-resistant flare of ulcerative colitis. He subsequently developed fever, with genital and oral ulcerations. He was hospitalized for diabetic decompensation with massive elevation of serum aminotransferases. Examination revealed vesicles on the hands. Liver biopsy showed Cowdry type B inclusions. Therapy with acyclovir was immediately initiated and the patient recovered. This case illustrates the diagnostic importance of mucocutaneous lesions in the assessment of complications after liver transplantation. PMID:14614611

  8. Herpes Simplex Virus Oncolytic Therapy for Pediatric Malignancies

    PubMed Central

    Friedman, Gregory K; Pressey, Joseph G; Reddy, Alyssa T; Markert, James M; Gillespie, G Yancey

    2009-01-01

    Despite improving survival rates for children with cancer, a subset of patients exist with disease resistant to traditional therapies such as surgery, chemotherapy, and radiation. These patients require newer, targeted treatments used alone or in combination with more traditional approaches. Oncolytic herpes simplex virus (HSV) is one of these newer therapies that offer promise for several difficult to treat pediatric malignancies. The potential benefit of HSV therapy in pediatric solid tumors including brain tumors, neuroblastomas, and sarcomas is reviewed along with the many challenges that need to be addressed prior to moving oncolytic HSV therapy from the laboratory to the beside in the pediatric population. PMID:19367259

  9. Stimulation of human lymphocytes by Herpes simplex virus antigens.

    PubMed Central

    Starr, S E; Karatela, S A; Shore, S L; Duffey, A; Nahmias, A J

    1975-01-01

    Lymphocytes from individuals with laboratory evidence of prior infection with herpes simplex virus (HSV) type 1 or type 2 demonstrated transformation (av antigens. Higher stimulation indexes were obtained when lymphocytes were incubated with the homologous as compared with the heterologous antigen. Higher mean lymphocyte stimulation indexes were also demonstrated in seropositive as compared with seronegative individuals. Lymphocytes from children with HSV-1 stomatitis usually became responsive to HSV-1 antigen within 2 to 6 weeks after the onset of illness. Lymphocytes from infants with neonatal HSV-2 infection were stimulated by HSV-2 antigen. PMID:163788

  10. 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

  11. Novel agents and strategies to treat herpes simplex virus infections.

    PubMed

    Kleymann, Gerald

    2003-02-01

    The quiet pandemic of herpes simplex virus (HSV) infection has plagued humanity since ancient times, causing mucocutaneous infection, such as herpes labialis and herpes genitalis. Disease symptoms often interfere with everyday activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immunocompromised patient population. After primary or initial infection the virus persists for life in a latent form in neurons of the host, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently, no cure is available. In the mid-1950s the first antiviral, idoxuridine, was developed for topical treatment of herpes disease and, in 1978, vidarabine was licensed for systemic use to treat HSV encephalitis. Acyclovir (Zovirax), a potent, specific and tolerable nucleosidic inhibitor of the herpes DNA polymerase, was a milestone in the development of antiviral drugs in the late 1970s. In the mid-1990s, when acyclovir became a generic drug, valacyclovir (Valtrex) and famciclovir (Famvir), prodrugs of the gold standard and penciclovir (Denavir), Vectavir), a close analogue, were launched. Though numerous approaches and strategies were tested and considerable effort was expended in the search of the next generation of an antiherpetic therapy, it proved difficult to outperform acyclovir. Notable in this regard was the award of a Nobel Prize in 1988 for the elucidation of mechanistic principles which resulted in the development of new drugs such as acyclovir. Vaccines, interleukins, interferons, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or nonspecific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. Recently though, new inhibitors of the HSV helicase-primase with potent in vitro

  12. A Case Series: Herpes Simplex Virus as an Occupational Hazard

    PubMed Central

    Browning, William D; McCarthy, James P

    2012-01-01

    Statement of the Problem Herpes labialis infections are common and present a serious risk to the dental team. Purpose of the Study The purpose is to make dentists aware of the risks involved with treatment of patients with active herpes labialis. In addition, evidence-based risk-management strategies are presented. Methods and Materials The incidence and natural history of herpes simplex virus type 1 (HSV-1) are reviewed. Four previously unreported case histories are presented to illustrate the impact common sequelae of HSV-1 can have on the dental team. The differences between HSV-1 and the blood-borne diseases which are the focus of universal precautions are discussed. In particular, the highly contagious, highly transmissible nature of HSV-1 and its transmission through aerosols are highlighted. Finally, the need to include protection against aerosols in the profession's understanding of universal precautions is noted. Results The authors suggest limiting the treatment of patients with active lesions to urgent care only, and treating active HSV-1 lesions to reduce time of healing. For four common clinical situations involving HSV-1 infections, evidence-based methods for protecting the dental team and the patient from cross-contamination are also presented. Conclusion While it is clear that the treatment of patients with active herpes labialis lesions increases risk of cross-infection, there are good protocols for controlling this risk. CLINICAL SIGNIFICANCE By bringing common vectors of cross-infection to light and providing evidence-based protocols for preventing them, this article provides practitioners with positive steps that can be taken for controlling the risk of spreading herpes infections to the dental team. (J Esthet Restor Dent 24:61–67, 2012) PMID:22296698

  13. 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

  14. The inhibitory effect of essential oils on herpes simplex virus type-1 replication in vitro.

    PubMed

    Minami, Masato; Kita, Masakazu; Nakaya, Takaaki; Yamamoto, Toshiro; Kuriyama, Hiroko; Imanishi, Jiro

    2003-01-01

    The antiviral effect of 12 essential oils on herpes simplex virus type-1 (HSV-1) replication was examined in vitro. The replication ability of HSV-1 was suppressed by incubation of HSV-1 with 1% essential oils at 4 C for 24 hr. Especially, lemongrass completely inhibited the viral replication even at a concentration of 0.1%, and its antiviral activity was dependent on the concentrations of the essential oil. When Vero cells were treated with the essential oil before or after viral adsorption, no antiviral activity was found, which suggests that the antiviral activity of essential oils including lemongrass may be due to the direct interaction with virions. PMID:14584615

  15. Preventing herpes simplex virus transmission to the neonate.

    PubMed

    Brown, Zane

    2004-08-01

    Neonatal herpes simplex virus (HSV) infection can have severe consequences. Skin, eye and mouth infection is rarely fatal, but disseminated or central nervous system (CNS) disease has a mortality rate of 80% in the absence of therapy, and most surviving infants have neurological sequelae. Aciclovir therapy can improve the outcome of neonatal herpes, but is often delayed due to the early non-specific symptoms of the disease. Even with early therapy, some infants develop disseminated infection or CNS complications. The virus is usually vertically transmitted to the neonate from an infected mother during delivery. As such, the optimal strategy for reducing the morbidity of neonatal herpes is to prevent the neonate from acquiring HSV infection at delivery. The highest risk of neonatal infection occurs when the mother sheds HSV at labour, which happens more frequently in women who acquire genital herpes in the third trimester. Therefore, one approach for reducing maternal-fetal transmissions is to prevent HSV acquisition in late pregnancy. Definitive classification of genital HSV infection during pregnancy as either primary, non-primary first episode or recurrent can be accomplished only when clinical evaluation is accompanied by laboratory testing, including the use of gG-specific serological tests. The serological status of the mother's sexual partner should be considered when determining her risk of infection. The use of weekly viral cultures in pregnant women with confirmed genital herpes is not warranted, as they do not predict an infant's risk of acquisition of HSV at delivery and are not cost-effective. High-risk susceptible women should be counselled about abstinence and reducing oral-genital contact near term. Observational studies suggest that caesarean section can reduce transmission of neonatal herpes, and is warranted for women who shed HSV at delivery, although different countries vary in their approach to caesarean sections and so universal

  16. Effect of the ionophore monensin on herpes simplex virus type 1-induced cell fusion, glycoprotein synthesis, and virion infectivity.

    PubMed

    Kousoulas, K G; Bzik, D J; Person, S

    1983-01-01

    The ionophore monensin inhibited the formation of mature, fully glycosylated glycoproteins gB, gC, and gD during herpes simplex virus type 1 infection of human embryonic lung cells. Underglycosylated forms, including the apparent high-mannose precursor forms of the major glycoproteins, appeared. Monensin inhibited virus-induced cell fusion. Infectious virions produced in the presence of monensin appeared to contain predominantly underglycosylated glycoproteins. PMID:6307921

  17. 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.

  18. Isolation of a protein kinase induced by herpes simplex virus type 1

    SciTech Connect

    Blue, W.T.; Stobbs, D.G.

    1981-04-01

    Researchers have isolated a new cyclic AMP-independent protein kinase activity induced in HeLa cells by infection with herpes simplex virus type 1. Induction of the enzyme does not occur in cells treated with cycloheximide at the time of infection, or in cells infected with UV-inactivated herpes simplex virus type 1. The amount of enzyme induced in infected cells is dependent upon the multiplicity of infection. An enzyme with identical properties to the appearing in infected HeLa cells is also induced by herpes simplex virus type 1 in BHK cells.

  19. Inhibition of herpes simplex type 1 and type 2 infections by Oximacro(®), a cranberry extract with a high content of A-type proanthocyanidins (PACs-A).

    PubMed

    Terlizzi, Maria Elena; Occhipinti, Andrea; Luganini, Anna; Maffei, Massimo E; Gribaudo, Giorgio

    2016-08-01

    In the absence of efficient preventive vaccines, topical microbicides offer an attractive alternative in the prevention of Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. Because of their recognized anti-adhesive activity against bacterial pathogens, cranberry (Vaccinium macrocarpon Ait.) extracts may represent a natural source of new antiviral microbicides. However, few studies have addressed the applications of cranberry extract as a direct-acting antiviral agent. Here, we report on the ability of the novel cranberry extract Oximacro(®) and its purified A-type proanthocyanidins (PACs-A), to inhibit HSV-1 and HSV-2 replication in vitro. Analysis of the mode of action revealed that Oximacro(®) prevents adsorption of HSV-1 and HSV-2 to target cells. Further mechanistic studies confirmed that Oximacro(®) and its PACs-A target the viral envelope glycoproteins gD and gB, thus resulting in the loss of infectivity of HSV particles. Moreover, Oximacro(®) completely retained its anti-HSV activity even at acidic pHs (3.0 and 4.0) and in the presence of 10% human serum proteins; conditions that mimic the physiological properties of the vagina - a potential therapeutic location for Oximacro(®). Taken together, these findings indicate Oximacro(®) as an attractive candidate for the development of novel microbicides of natural origin for the prevention of HSV infections. PMID:27321663

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

    PubMed Central

    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. PMID:25320695

  1. PARAMETERS DISTINGUISHING HERPES SIMPLEX VIRUS TYPE 2-TRANSFORMED TUMORIGENIC AND NONTUMORIGENIC RAT CELLS

    EPA Science Inventory

    A newly developed experimental model system was used to determine in vitro transformation-specific parameters which correlate with tumorigenicity. The data suggested that clonal herpes simplex virus type 2-transformed syngeneic rat embryo cells with intermediate, transformed rat ...

  2. Detection of herpes simplex virus-specific DNA sequences in latently infected mice and in humans.

    PubMed Central

    Efstathiou, S; Minson, A C; Field, H J; Anderson, J R; Wildy, P

    1986-01-01

    Herpes simplex virus-specific DNA sequences have been detected by Southern hybridization analysis in both central and peripheral nervous system tissues of latently infected mice. We have detected virus-specific sequences corresponding to the junction fragment but not the genomic termini, an observation first made by Rock and Fraser (Nature [London] 302:523-525, 1983). This "endless" herpes simplex virus DNA is both qualitatively and quantitatively stable in mouse neural tissue analyzed over a 4-month period. In addition, examination of DNA extracted from human trigeminal ganglia has shown herpes simplex virus DNA to be present in an "endless" form similar to that found in the mouse model system. Further restriction enzyme analysis of latently infected mouse brainstem and human trigeminal DNA has shown that this "endless" herpes simplex virus DNA is present in all four isomeric configurations. Images PMID:3003377

  3. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

    SciTech Connect

    Perna, J.J.; Mannix, M.L.; Rooney, J.F.; Notkins, A.L.; Straus, S.E.

    1987-09-01

    Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation.

  4. Fulminant hepatitis following primary herpes simplex virus infection.

    PubMed

    Al Midani, A; Pinney, J; Field, N; Atkinson, C; Haque, T; Harber, M

    2011-01-01

    Fulminant hepatic failure (FHF) is a rare but well-recognized complication of primary herpes simplex virus (HSV) infection in immunocompromised patients. Here, we report two cases of acute hepatitis and FHF secondary to primary HSV type 1 infection following renal transplantation in the absence of any mucocutaneous manifestation. High levels of HSV type-1 DNA were detected in the blood. Both patients were seronegative for HSV 1 and HSV 2 immunoglobulin G (IgG) before transplantation, whereas the donor of patient 1 was HSV 1 IgG-positive but had no viremia and the donor of patient 2 was HSV-seronegative. Patient 1 recovered with acyclovir and immunoglobulin whereas patient 2 did not respond and succumbed to death. HSV-seronegative patients are potentially at risk of developing severe primary HSV disease following transplantation, particularly in the absence of routine anti-viral prophylaxis. HSV infection should always be excluded in transplant patients with hepatic dysfunction. PMID:21196623

  5. 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

  6. 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

  7. Chromatin assembly on herpes simplex virus genomes during lytic infection

    PubMed Central

    Lu, Xu; Triezenberg, Steven J

    2009-01-01

    The human herpes simplex viruses HSV-1 and HSV-2 infect a significant portion of the human population. Both viruses can undergo lytic infection in epithelial cells and establish lifelong latency in neuronal cells. The large HSV-1 DNA genomes have long been considered to be devoid of histones both inside the virion particle and inside the cell during lytic infection, but to be packaged in repressive chromatin during latency. However, recent reports indicate that many histone and non-histone chromosomal proteins can associate with viral DNA during lytic infection and may influence important events during the HSV-1 lytic cycle. In this article, we summarize recent developments in this field and their implications. PMID:19682614

  8. Encephalitis herpes simplex: aural rehabilitation following bilateral deafness.

    PubMed

    Montano, J J; Melley, C C; Karam, D B

    1983-10-01

    Aural rehabilitation is a critical and often neglected aspect of a hearing-impaired patient's total rehabilitation. This case description illustrates the need for implementation of aural rehabilitation services. A 59-year-old woman exhibited bilateral profound sensorineural hearing loss following the onset of encephalitis herpes simplex. Auditory amplification attempts were unsuccessful. Aural rehabilitation was initiated immediately, and she was seen for lipreading and vibrotactile stimulation training. Goals progressed from identification of single words within a category to phonemic recognition. Vibrotactile stimulation was used to facilitate environmental awareness. Therapy goals reflected the patient's increased motivation to communicate within her environment. This patient's communicative status is viewed on a continuum: from success in individual treatment goals, extending to successful communication within the structure of the entire rehabilitation setting, and finally to functional communication within her home environment. PMID:6625883

  9. 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.

  10. Advance in herpes simplex viruses for cancer therapy.

    PubMed

    Liu, Shanglong; Dai, Meihua; You, Lei; Zhao, Yupei

    2013-04-01

    Oncolytic virotherapy is an attractive approach that uses live viruses to selectively kill cancer cells. Oncolytic viruses can be genetically engineered to induce cell lyses through virus replication and cytotoxic protein expression. Herpes simplex virus (HSV) has become one of the most widely clinically used oncolytic agent. Various types of HSV have been studied in basic or clinical research. Combining oncolytic virotherapy with chemotherapy or radiotherapy generally produces synergic action with unclear molecular mechanisms. Arming HSV with therapeutic transgenes is a promising strategy and can be used to complement conventional therapies. As an efficient gene delivery system, HSV has been successfully used to deliver various immunomodulatory molecules. Arming HSV with therapeutic genes merits further investigation for potential clinical application. PMID:23564184

  11. 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

  12. 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

  13. 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. PMID:27224245

  14. 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

  15. 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…

  16. 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. PMID:27171680

  17. Hypomethylation of host cell DNA synthesized after infection or transformation of cells by herpes simplex virus

    SciTech Connect

    Macnab, J.C.M.; Adams, R.L.P.; Rinaldi, A.; Orr, A.; Clark, L.

    1988-04-01

    Infection of rat embryo cells with herpes simplex virus type 2 caused undermethylation of host cell DNA synthesized during infection. DNA made prior to infection was not demethylated, but some of its degradation products, including methyl dCMP, were incorporated into viral DNA. The use of mutant virus showed that some viral DNA synthesis appears to be required for the inhibition of methylation. Inhibition of methylation cannot be explained by an absence of DNA methyltransferase as the activity of this enzyme did not change during the early period of infection. Inhibition of host cell DNA methylation may be an important step in the transformation of cells by herpesviruses, and various transformed cell lines tested showed reduced levels of DNA methylation.

  18. Successful treatment of hypertrophic herpes simplex genitalis in HIV-infected patient with topical imiquimod.

    PubMed

    Deza, Gustavo; Martin-Ezquerra, Gemma; Curto-Barredo, Laia; Villar García, Judit; Pujol, Ramon M

    2015-12-01

    Hypertrophic herpes simplex genitalis is an atypical presentation of genital herpes described in the context of immunosuppression, particularly HIV-positive patients. This situation can become a diagnostic and therapeutic challenge. For this reason, alternative therapies are currently being discussed in the literature. We report a case of hypertrophic genital herpes in a HIV-positive patient who was successfully treated with topical 5% imiquimod after treatment failures with oral and i.v. antivirals. PMID:26074211

  19. Treatment of colon cancer with oncolytic herpes simplex virus in preclinical models.

    PubMed

    Yang, H; Peng, T; Li, J; Wang, Y; Zhang, W; Zhang, P; Peng, S; Du, T; Li, Y; Yan, Q; Liu, B

    2016-05-01

    Cancer stem cells (CSCs), which are a rare population in any type of cancer, including colon cancer, are tumorigenic and responsible for cancer recurrence and metastasis. CSCs have been isolated from a number of different solid tumors recently, although the isolation of CSCs in colon cancer is still challenging. We cultured colon cancer cells in stem cell medium to obtain colonosphere cells. These cells possessed the characteristics of CSCs, with a high capacity of tumorigenicity, migration and invasion in vitro and in vivo. The isolation and identification of CSCs have provided new targets for the therapeutics. Oncolytic herpes simplex viruses (oHSV) are an effective strategy for killing colon cancer cells in preclinical models. Here, we examined the efficacy of an oncolytic herpes simplex virus type 2 (oHSV2) in killing colon cancer cells and colon cancer stem-like cells (CSLCs). oHSV2 was found to be highly cytotoxic to the adherent and sphere cells in vitro, and oHSV2 treatment in vivo significantly inhibited tumor growth. This study demonstrates that oHSV2 is effective against colon cancer cells and colon CSLCs and could be a promising strategy for treating colon cancer patients. PMID:26871935

  20. Herpes simplex virus colitis complicating ulcerative colitis: A case report and brief review on superinfections.

    PubMed

    Schunter, Marco Oliver; Walles, Thorsten; Fritz, Peter; Meyding-Lamadé, Uta; Thon, Klaus-Peter; Fellermann, Klaus; Stange, Eduard Friedrich; Lamadé, Wolfram

    2007-09-01

    In patients with inflammatory bowel disease herpes simplex virus infection has been described as a major cause of morbidity and mortality, especially in immunocompromised individuals. Here we present the case of a 35-year old woman with an exacerbation of ulcerative colitis caused by herlpes simplex virus infection (HSV-2). The diagnosis was confirmed histologically following subtotal colectomy. After intravenous treatment with aciclovir for 2 weeks postoperative hematochezia stopped. Herpes simplex virus colitis is a rare but potentially fatal complication of immunosuppressive treatment in patients with inflammatory bowel disease. Prompt diagnosis and efficient antiviral therapy are mandatory to improve prognosis. PMID:21172183

  1. 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

  2. Differential stability of host mRNAs in Friend erythroleukemia cells infected with herpes simplex virus type 1

    SciTech Connect

    Mayman, B.A.; Nishioka, Y.

    1985-01-01

    The consequences of herpes simplex virus type 1 infection on cellular macromolecules were investigated in Friend erythroleukemia cells. The patterns of protein synthesis, examined by polyacrylamide gel electrophoresis, demonstrated that by 4 h postinfection the synthesis of many host proteins, with the exception of histones, was inhibited. Examination of the steady-state level of histone H3 mRNA by molecular hybridization of total RNA to a cloned mouse histone H3 complementary DNA probe demonstrated that the ratio of histone H3 mRNA to total RNA remained unchanged for the first 4 h postinfection. In contrast, the steady-state levels of globin and actin mRNAs decreased progressively at early intervals postinfection. Studies on RNA synthesis in isolated nuclei demonstrated that the transcription of the histone H3 gene was inhibited to approximately the same extent as that of actin gene. It was concluded that the stabilization of preexisting histone H3 mRNA was responsible for the persistence of H3 mRNA and histone protein synthesis in herpes simplex virus type 1-infected Friend erythroleukemia cells. The possible mechanisms influencing the differential stability of host mRNAs during the course of productive infection with herpes simplex virus type 1 are discussed.

  3. Involvement of DNA polymerase alpha in host cell reactivation of UV-irradiated herpes simplex virus

    SciTech Connect

    Nishiyama, Y.; Yoshida, S.; Maeno, K.

    1984-02-01

    Aphidicolin is a potent inhibitor of both host cell DNA polymerase alpha and herpes simplex virus (HSV)-induced DNA polymerase but has no effect on DNA polymerases beta and gamma of host cells. By using an aphidicolin-resistant mutant (Aphr) of HSV, a possible involvement of DNA polymerase alpha in host cell reactivation of UV-damaged HSV was studied. Plaque formation by UV-irradiated Aphr was markedly inhibited by 1 microgram of aphidicolin per ml, which did not affect the plating efficiency of nonirradiated Aphr. Aphidicolin added before 12 h postinfection inhibited plaque formation by irradiated Aphr, which became aphidicolin insensitive after 36 h postinfection. The results strongly suggest that host cell DNA polymerase alpha is involved in the repair of UV-irradiated HSV DNA.

  4. The Vaginal Acquisition and Dissemination of HIV-1 Infection in a Novel Transgenic Mouse Model Is Facilitated by Coinfection with Herpes Simplex Virus 2 and Is Inhibited by Microbicide Treatment

    PubMed Central

    Seay, Kieran; Khajoueinejad, Nazanin; Zheng, Jian Hua; Kiser, Patrick; Ochsenbauer, Christina; Kappes, John C.; Herold, Betsy

    2015-01-01

    have reported that genital herpes simplex virus 2 (HSV-2) infection increases the risk of HIV-1 sexual acquisition by severalfold. Understanding the underlying mechanisms by which HSV-2 facilitates HIV-1 infection and optimizing the efficacy of therapies to inhibit HIV-1 infection during HSV-2 coinfection should contribute to reducing HIV-1 transmission. Using our novel transgenic hCD4/R5/cT1 mouse model infectible with HIV-1, we demonstrated that HSV-2 infection enhances vaginal transmission and dissemination of HIV-1 infection while stimulating recruitment and activation of CD4+ T cells and dendritic cells in the lower genital tract. HIV acquisition by hCD4/R5/cT1 mice vaginally coinfected with HSV-2 could be completely prevented in almost half the mice by preexposure prophylaxis (PrEP) with a novel gel containing tenofovir disoproxil fumarate (TDF), the tenofovir prodrug, but not with the tenofovir microbicide gel utilized in CAPRISA-004, VOICE, and FACTS-001 clinical trials. The hCD4/R5/cT1 mice represent a new preclinical mouse model to evaluate vaginal HIV-1 acquisition. PMID:26157126

  5. 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

  6. 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

  7. 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. PMID:26243746

  8. The herpes simplex virus virion host shutoff function.

    PubMed Central

    Kwong, A D; Frenkel, N

    1989-01-01

    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. Images PMID:2552156

  9. 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

  10. Herpes simplex virus encephalitis in Peru: a multicentre prospective study.

    PubMed

    Montano, S M; Mori, N; Nelson, C A; Ton, T G N; Celis, V; Ticona, E; Sihuincha, M; Tilley, D H; Kochel, T; Zunt, J R

    2016-06-01

    Herpes simplex virus (HSV) is one of the most commonly identified infectious aetiologies of encephalitis in North America and Europe. The epidemiology of encephalitis beyond these regions, however, is poorly defined. During 2009-2012 we enrolled 313 patients in a multicentre prospective study of encephalitis in Peru, 45 (14·4%) of whom had confirmed HSV infection. Of 38 patients with known HSV type, 84% had HSV-1 and 16% had HSV-2. Patients with HSV infection were significantly more likely to present in the summer months (44·4% vs. 20·0%, P = 0·003) and have nausea (60·0% vs. 39·8%, P = 0·01) and rash (15·6% vs. 5·3%, P = 0·01) compared to patients without HSV infection. These findings highlight differences in the epidemiology and clinical presentation of HSV encephalitis outside of the Northern Hemisphere that warrant further investigation. Furthermore, there is an urgent need for improved HSV diagnostic capacity and availability of intravenous acyclovir in Peru. PMID:26733400

  11. Herpes Simplex Virus Products in Productive and Abortive Infection

    PubMed Central

    Spring, Susan B.; Roizman, Bernard; Schwartz, Jerome

    1968-01-01

    Herpes simplex virus strain MPdk− multiplies in HEp-2 cells, but not in dog kidney (DK) cells. Strain MPdk+sp, a multistep mutant of MPdk−, multiplies in both HEp-2 and DK cells. Stabilized lysates of productively infected cells yield three macromolecular aggregates of viral deoxyribonucleic acid and protein banding in CsCl gradients at densities of 1.285 g/cm3 (α), 1.325 g/cm3 (β), and 1.37 to 1.45 g/cm3 (γ). Similar lysates from abortively infected cells yield only the β and γ bands. Electron microscopic examination revealed that (i) the α band contained enveloped nucleocapsids, whereas the β band contained naked nucleocapsids and particles tentatively identified as internal components of the nucleocapsids, and that (ii) the enveloped virions and reduplication of cellular membranes observed in thin sections of productively infected cells were absent from abortively infected cells. Studies of the surface antigens of infected cells in a cytolytic system described previously revealed that abortively infected cells contained approximately 10-fold less virus-induced surface antigen than did productively infected cells. From these and other data published previously, we concluded that infectious MPdk− virions are not made in DK cells because (i) functional viral products necessary for the envelopment of the nucleocapsid are not made, and (ii) capsid proteins and some nonstructural products specified by the virus malfunction. Images PMID:4316018

  12. Cervical cancer: is herpes simplex virus type II a cofactor?

    PubMed Central

    Jones, C

    1995-01-01

    In many ways, cervical cancer behaves as a sexually transmitted disease. The major risk factors are multiple sexual partners and early onset of sexual activity. Although high-risk types of human papillomaviruses (HPV) play an important role in the development of nearly all cases of cervical cancer, other sexually transmitted infectious agents may be cofactors. Herpes simplex virus type 2 (HSV-2) is transmitted primarily by sexual contact and therefore has been implicated as a risk factor. Several independent studies suggest that HSV-2 infections correlate with a higher than normal incidence of cervical cancer. In contrast, other epidemiological studies have concluded that infection with HSV-2 is not a major risk factor. Two separate transforming domains have been identified within the HSV-2 genome, but continued viral gene expression apparently is not necessary for neoplastic transformation. HSV infections lead to unscheduled cellular DNA synthesis, chromosomal amplifications, and mutations. These observations suggest that HSV-2 is not a typical DNA tumor virus. It is hypothesized that persistent or abortive infections induce permanent genetic alterations that interfere with differentiation of cervical epithelium and subsequently induce abnormal proliferation. Thus, HSV-2 may be a cofactor in some but not all cases of cervical cancer. PMID:8665469

  13. Higher Throughput Quantification of Neutralizing Antibody to Herpes Simplex Viruses

    PubMed Central

    Blevins, Tamara P.; Mitchell, Michelle C.; Korom, Maria; Wang, Hong; Yu, Yinyi; Morrison, Lynda A.; Belshe, Robert B.

    2015-01-01

    We report a rapid, higher throughput method for measuring neutralizing antibody to herpes simplex virus (HSV) in human sera. Clinical isolates and sera from the Herpevac Trial for Women were used in a colorimetric assay in which infection of tissue culture (lack of neutralization) was indicated by substrate metabolism by beta-galactosidase induced in the ELVIS cell line. The neutralization assay was optimized by addition of guinea pig complement, which particularly enhanced neutralizing antibody titers to HSV-2. Higher neutralizing antibody titers were also achieved using virus particles isolated from the supernatant of infected cells rather than lysate of infected cells as the source of virus. The effect of assay incubation time and incubation time with substrate were also optimized. We found that incubating with substrate until a standard optical density of 1.0 was reached permitted a better comparison among virus isolates, and achieved reliable measurement of neutralizing antibody activity. Interestingly, in contrast to results in the absence of complement, addition of complement allowed sera from HSV-2 gD-vaccinated subjects to neutralize HSV-1 and HSV-2 clinical and laboratory isolates with equal potency. PMID:26658766

  14. Seroreactive recombinant herpes simplex virus type 2-specific glycoprotein G.

    PubMed Central

    Parkes, D L; Smith, C M; Rose, J M; Brandis, J; Coates, S R

    1991-01-01

    The herpes simplex virus type 2 (HSV-2) genome codes for an envelope protein, glycoprotein G (gG), which contains predominantly type 2-specific epitopes. A portion of this gG gene has been expressed as a fusion protein in Escherichia coli. Expression was regulated by a lambda phage pL promoter. The 60,000-molecular-weight recombinant protein was purified by ion-exchange chromatography. Amino acid sequence analysis confirmed the N terminus of the purified protein. Mice immunized with recombinant gG developed antibodies reactive with native HSV-2 protein, but not with HSV-1 protein, in an indirect immunofluorescence assay. The serological activity of this purified recombinant gG protein was evaluated by immunoblot assay. This protein was reactive with an HSV-2 gG monoclonal antibody. It was also reactive with HSV-2 rabbit antiserum but not with HSV-1 rabbit antiserum. Of 15 patient serum samples known to have antibody to HSV-2, 14 were reactive with this recombinant type 2-specific gG protein, and none of 15 HSV antibody-negative patient serum samples showed reactivity. In agreement with the expected prevalence of HSV-2 infection, 27.6% of 134 serum samples from random normal individuals had antibodies reactive with recombinant gG. This recombinant gG protein may be of value in detecting HSV-2-specific antibody responses in patients infected with HSV-2. Images PMID:1653787

  15. Clinical Correlates of Herpes Simplex Virus Viremia Among Hospitalized Adults

    PubMed Central

    Berrington, William R.; Jerome, Keith R.; Cook, Linda; Wald, Anna; Corey, Lawrence; Casper, Corey

    2009-01-01

    Background The quantification of herpes simplex virus (HSV) DNA from the peripheral blood is often used to evaluate patients suspected of having disseminated HSV infection. Few studies have examined the clinical correlates of HSV viremia among adults. Methods We conducted a retrospective analysis of blood samples sent to a reference molecular virology diagnostic facility at a university hospital for quantification of HSV DNA between October 2001 and June 2006. Medical records of patients with detectable HSV DNA were reviewed to abstract relevant clinical characteristics. Results HSV DNA was detected in 37 (4.0%) of 951 samples from 29 individual patients. 19 (65.5%) were >16 years of age, and detailed medical records were available for review from 13 (68.4%) of 19 adults patients. Of the 10 patients whose HSV infection was typed, 6 (60%) had HSV-2, 3 (30%) had HSV-1, and one had evidence of both HSV-1 and HSV-2 infection. All viremic patients were treated with antiviral medications. The most common clinical findings were hepatitis (62%), fever (54%), CNS alterations (46%), skin lesions (38%), abdominal pain (31%), and sepsis (31%). Respiratory failure (23%) was uncommon. Patients with HSV viremia were observed to have a high mortality rate (6 of 10 immunocompromised and 1 of 3 immunocompetent individuals). Conclusions HSV viremia may be associated with a variety of morbid signs and symptoms in hospitalized immunocompetent and immunocompromised adults, and is associated with high rates of mortality, though causality can only be determined by additional studies. PMID:19807272

  16. 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

  17. Higher Throughput Quantification of Neutralizing Antibody to Herpes Simplex Viruses.

    PubMed

    Blevins, Tamara P; Mitchell, Michelle C; Korom, Maria; Wang, Hong; Yu, Yinyi; Morrison, Lynda A; Belshe, Robert B

    2015-01-01

    We report a rapid, higher throughput method for measuring neutralizing antibody to herpes simplex virus (HSV) in human sera. Clinical isolates and sera from the Herpevac Trial for Women were used in a colorimetric assay in which infection of tissue culture (lack of neutralization) was indicated by substrate metabolism by beta-galactosidase induced in the ELVIS cell line. The neutralization assay was optimized by addition of guinea pig complement, which particularly enhanced neutralizing antibody titers to HSV-2. Higher neutralizing antibody titers were also achieved using virus particles isolated from the supernatant of infected cells rather than lysate of infected cells as the source of virus. The effect of assay incubation time and incubation time with substrate were also optimized. We found that incubating with substrate until a standard optical density of 1.0 was reached permitted a better comparison among virus isolates, and achieved reliable measurement of neutralizing antibody activity. Interestingly, in contrast to results in the absence of complement, addition of complement allowed sera from HSV-2 gD-vaccinated subjects to neutralize HSV-1 and HSV-2 clinical and laboratory isolates with equal potency. PMID:26658766

  18. 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.

  19. Treatment of Herpes simplex virus infections with topical antiviral agents.

    PubMed

    Hamuy, R; Berman, B

    1998-01-01

    Clinical studies of topical therapy against Herpes simplex virus (HSV) infections have been reviewed. Idoxuridine (IDU) 15% in dimethyl sulfoxide (DMSO), interferons, and penciclovir result in significant clinical benefit against this virus. IDU reduced pain duration and decreased time to loss of crust in a study of 301 patients. Alpha-interferon has shown synergism with other anti-HSV drugs such as caffeine, trifluorothymidine (TFT), DMSO, and nonoxynol-9. Finally, in a study of over 2,000 patients, application of penciclovir cream, both early and late in the course of HSV infection, decreased the duration of lesions, pain, and viral shedding. Acyclovir (ACV)-resistant strains of HSV are susceptible to (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and ascorbic acid shows promising effects against HSV. Using a vehicle that enhances skin penetration of a drug or possibly further exploring combination therapy may result in efficacious treatment of HSV. The possibility of topical vaccination or topical gene therapy may also prove beneficial in the future. PMID:9683881

  20. 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.

  1. Cutaneous Co-infected Cytomegalovirus and Herpes Simplex Virus Perigenital Ulcers in Human Immunodeficiency Virus Patients.

    PubMed

    Schoenfeld, Jason; Cannon, Sarah; Cam, Kristin; Keller, Matthew

    2013-10-01

    There is uncertainty regarding the pathogenic nature of cytomegalovirus in cutaneous lesions co-infected with herpes simplex virus. It is widely believed that herpes simplex virus is the main pathogenic factor in such lesions and that cytomegalovirus plays little if any role. There are, however, isolated case reports that describe cytomegalovirus as an important driving pathogen in such lesions. The authors present two human immunodeficiency virus patients who have cytomegalovirus and herpes simplex virus co-infected perigenital ulcers, one of whom improved on valacyclovir, while the other, who was already on valacyclovir for chronic herpes simplex virus suppression, showed no improvement with a single dose of cidofovir. He only showed rapid improvement when treated with valganciclovir. The latter patient underscores the viewpoint that at least in some cases, cytomegalovirus may be an important driving force behind the formation of such lesions. The authors therefore recommend that clinicians be aware of the possible pathogenic role of cytomegalovirus in these ulcers, and, in nonhealing ulcers, use anti-cytomegalovirus agents to prevent the onset of systemic disease. These results warrant further study of the pathogenesis of cytomegalovirus in co-infected herpes simplex virus ulcers. PMID:24155993

  2. Antiviral activity of the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2.

    PubMed

    Allahverdiyev, A; Duran, N; Ozguven, M; Koltas, S

    2004-11-01

    Melissa officinalis L. (Lamiaceae) has been used in a variety of practical applications in medical science. Our objective in the current study was to determine the effects of the volatile oil components of M. officinalis on Herpes simplex virus type 2 (HSV-2) replication in HEp-2 cells. Four different concentrations (25, 50, 100, 150 and 200 microg/ml) of volatile oils were examined. Experiments were carried out using HEp-2 cells. M. officinalis volatile oil was found to be non-toxic to HEp-2 cells up to a concentration of 100 micro/ml. It was, however, found to be slightly toxic at a concentration over of 100 microg/ml. The antiviral activity of non-toxic concentrations against HSV-2 was tested. The replication of HSV-2 was inhibited, indicating that the M. officinalis L. extract contains an anti-HSV-2 substance. PMID:15636181

  3. 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. PMID:27241721

  4. Stable erythrocyte diagnostic preparation for passive haemagglutination test with herpes simplex virus antigen.

    PubMed

    Krichevskaya, G I; Basova, N N

    1976-10-01

    A method for the preparation of stable suspensions of erythrocytes sensitized with herpes simplex virus (HSV) antigen and for their use in the passive haemagglutination test (PHAT) was developed. Formolized sheep erythrocytes were treated with tannin and sensitized with HSV antigen prepared from infected chick embryo cell culture by ultrasonication and virus extraction with alkaline glycine buffer. Antibody titres determined in the PHAT were higher than titres of neutralizing antibody. The specificity of the results was checked by the passive haemagglutination-inhibition test (PHAIT). The sensitized erythrocytes retained their activity for 5 months (the observation period) and gave reproducible results. The availability of stable erythrocyte diagnostic preparations simplifies the detection of herpesvirus antibody and makes the method widely applicable. PMID:11670

  5. 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

  6. Polyhydroxylated sulfated steroids derived from 5α-cholestanes as antiviral agents against herpes simplex virus.

    PubMed

    Pujol, Carlos A; Sepúlveda, Claudia S; Richmond, Victoria; Maier, Marta S; Damonte, Elsa B

    2016-07-01

    Twelve polyhydroxylated sulfated steroids synthesized from a 5α-cholestane skeleton with different substitutions in C-2, C-3 and C-6 were evaluated for cytotoxicity and antiviral activity against herpes simplex virus (HSV) by a virus plaque reduction assay. Four compounds elicited a selective inhibitory effect against HSV. The disodium salt of 2β,3α-dihydroxy-6E-hydroximine-5α-cholestane-2,3-disulfate, named compound 7, was the most effective inhibitor of HSV-1, HSV-2 and pseudorabies virus (PrV) strains, including acyclovir-resistant variants, in human and monkey cell lines. Preliminary mechanistic studies demonstrated that compound 7 did not affect the initial steps of virus entry but inhibited a subsequent event in the infection process of HSV. PMID:27101075

  7. In vitro virucidal activity of a styrylpyrone derivative against herpes simplex virus strain KOS-1

    NASA Astrophysics Data System (ADS)

    Moses, Micheal; Nor, Norefrina Shafinaz Md.; Ibrahim, Nazlina

    2014-09-01

    In this study, styrylpyrone derivative (SPD) extracted from Goniothalamus umbrosus root was tested against herpes simplex virus (HSV) strain KOS-1. Firstly, the cytotoxicity of SPD on Vero cells was tested and the value of cytotoxic concentration, CC50, was 44 μM (8.88 μg/mL), and the 50% Effective Concentration, EC50, was 3.35 μM (0.67 μg/mL). Selectivity index of SPD against HSV Kos-1 was more than 13 indicating potential as antiviral agent. Three treatments were used in the antiviral test; 1) post-treatment, 2) pre-treatment, and 3) virucidal. The results revealed that the post-treatment was more effective in inhibiting viral replication compared to pre-treatment. The findings indicated that the SPD from G. umbrosus has good potential for prospective nature-based antiviral drug.

  8. Structure and origin of defective genomes contained in serially passaged herpes simplex virus type 1 (Justin).

    PubMed Central

    Locker, H; Frenkel, N

    1979-01-01

    Restriction enzyme and hybridization analyses have revealed that high-density DNA prepared from passage 15 of serially passaged herpes simplex virus type 1 (Justin) contains three major classes of modified viral DNA molecules, each composed of distinct but closely related types of repeate units. The DNA sequences within the three types of repeat units are colinear with the DNA sequences located at the right end (between coordinates 0.94 and 1.0) of the parental herpes simplex virus type 1 genome. Thus, the three types of repeat units each contain the entire repeat sequence (ac) (which brackets the unique sequences of the small [S] component of herpes simplex virus type 1 DNA) and differ only with respect to the amount of unique S sequences which they contain. The three classes of high-density DNA molecules were found to be stably propagated between passages 6 and 15 of this series. Images PMID:221666

  9. Latency of Herpes Simplex Virus in Absence of Neutralizing Antibody: Model for Reactivation

    NASA Astrophysics Data System (ADS)

    Sekizawa, Tsuyoshi; Openshaw, Harry; Wohlenberg, Charles; Notkins, Abner Louis

    1980-11-01

    Mice inoculated with herpes simplex virus (type 1) by the lip or corneal route and then passively immunized with rabbit antibody to herpes simplex virus developed a latent infection in the trigeminal ganglia within 96 hours. Neutralizing antibody to herpes simplex virus was cleared from the circulation and could not be detected in most of these mice after 2 months. Examination of ganglia from the antibody-negative mice revealed latent virus in over 90 percent of the animals, indicating that serum neutralizing antibody is not necessary to maintain the latent state. When the lips or corneas of these mice were traumatized, viral reactivation occurred in up to 90 percent of the mice, as demonstrated by the appearance of neutralizing antibody. This study provides a model for identifying factors that trigger viral reactivation.

  10. 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

  11. 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

  12. Phosphonoacetic Acid-Resistant Herpes Simplex Virus Infection in Hairless Mice1

    PubMed Central

    Klein, Richard J.; Friedman-Kien, Alvin E.

    1975-01-01

    Phosphonoacetic acid (PAA)-resistant type 1 herpes simplex virus population was isolated by repeated passage of the virus in the presence of this inhibitor. Hairless mice infected percutaneously with the inhibitor-resistant or the parental inhibitor-susceptible virus were treated intraperitoneally with PAA and 9-β-d-arabinofuranosyl-adenine by using several different dosage schedules. Whereas 9-β-d-arabinofuranosyl-adenine was effective both in the PAA-susceptible and PAA-resistant herpes simplex virus-induced skin infection, PAA suppressed only the infection induced by the parental PAA-susceptible virus. PMID:166611

  13. Interactome analysis of herpes simplex virus 1 envelope glycoprotein H.

    PubMed

    Hirohata, Yoshitaka; Kato, Akihisa; Oyama, Masaaki; Kozuka-Hata, Hiroko; Koyanagi, Naoto; Arii, Jun; Kawaguchi, Yasushi

    2015-06-01

    Herpes simplex virus 1 (HSV-1) envelope glycoprotein H (gH) is important for viral entry into cells and nuclear egress of nucleocapsids. To clarify additional novel roles of gH during HSV-1 replication, host cell proteins that interact with gH were screened for by tandem affinity purification coupled with mass spectrometry-based proteomics in 293T cells transiently expressing gH. This screen identified 123 host cell proteins as potential gH interactors. Of these proteins, general control nonderepressive-1 (GCN1), a trans-acting positive effector of GCN2 kinase that regulates phosphorylation of the α subunit of translation initiation factor 2 (eIF2α), was subsequently confirmed to interact with gH in HSV-1-infected cells. eIF2α phosphorylation is known to downregulate protein synthesis, and various viruses have evolved mechanisms to prevent the accumulation of phosphorylated eIF2α in infected cells. Here, it was shown that GCN1 knockdown reduces phosphorylation of eIF2α in HSV-1-infected cells and that the gH-null mutation increases eIF2α in HSV-1-infected cells, whereas gH overexpression in the absence of other HSV-1 proteins reduces eIF2α phosphorylation. These findings suggest that GCN1 can regulate eIF2α phosphorylation in HSV-1-infected cells and that the GCN1-binding viral partner gH is necessary and sufficient to prevent the accumulation of phosphorylated eIF2α. Our database of 123 host cell proteins potentially interacting with gH will be useful for future studies aimed at unveiling further novel functions of gH and the roles of cellular proteins in HSV-1-infected cells. PMID:25808324

  14. 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.

  15. Chronic urticaria associated with recurrent genital herpes simplex infection and success of antiviral therapy--a report of two cases.

    PubMed

    Zawar, Vijay; Godse, Kiran; Sankalecha, Sudhir

    2010-06-01

    The role of infectious agents as a cause of chronic idiopathic urticaria (CIU) is uncertain. The objective of this study was to investigate whether genital herpes simplex infection is causally related to CIU. We identified two patients with recurrent genital herpes simplex infections associated with CIU. Episodes of genital herpes were especially associated with acute exacerbation of urticaria. Anti-herpes simplex 2 antibodies and Tzanck smears were done in both patients, along with other relevant investigations for CIU. Acyclovir was added to antihistamine therapy. Both patients were apparently in good health and appeared clinically immunologically stable, though one of them was found to be diabetic. Clinical and laboratory investigations for genital lesions supported a diagnosis of herpes simplex. Anti-herpes simplex 2 antibodies were markedly raised in both patients. The Tzanck smear was positive in one case and negative in the other, despite a definitive clinical diagnosis of herpes progenitalis. CIU, which was inadequately controlled with antihistamines alone, responded dramatically to the addition of acyclovir therapy. Our results may not be applicable to other patients with CIU, especially when there is inadequate evidence of an association with genital herpes. CIU may be associated with recurrent genital herpes simplex infection. In such situations, the addition of acyclovir to therapy may be beneficial. PMID:19699670

  16. The AGMA1 poly(amidoamine) inhibits the infectivity of herpes simplex virus in cell lines, in human cervicovaginal histocultures, and in vaginally infected mice.

    PubMed

    Donalisio, Manuela; Quaranta, Paola; Chiuppesi, Flavia; Pistello, Mauro; Cagno, Valeria; Cavalli, Roberta; Volante, Marco; Bugatti, Antonella; Rusnati, Marco; Ranucci, Elisabetta; Ferruti, Paolo; Lembo, David

    2016-04-01

    The development of topical microbicides is a valid approach to protect the genital mucosa from sexually transmitted infections that cannot be contained with effective vaccination, like HSV and HIV infections. A suitable target of microbicides is the interaction between viral proteins and cell surface heparan sulfate proteoglycans (HSPGs). AGMA1 is a prevailingly cationic agmatine-containing polyamidoamine polymer previously shown to inhibit HSPGs dependent viruses, including HSV-1, HSV-2, and HPV-16. The aim of this study was to elucidate the mechanism of action of AGMA1 against HSV infection and assess its antiviral efficacy and biocompatibility in preclinical models. The results show AGMA1 to be a non-toxic inhibitor of HSV infectivity in cell cultures and human cervicovaginal histocultures. Moreover, it significantly reduced the burden of infection of HSV-2 genital infection in mice. The investigation of the mechanism of action revealed that AGMA1 reduces cells susceptibility to virus infection by binding to cell surface HSPGs thereby preventing HSV attachment. This study indicates that AGMA1 is a promising candidate for the development of a topical microbicide to prevent sexually transmitted HSV infections. PMID:26854390

  17. 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

  18. Herpes simplex virus infection: part I--Biology, clinical presentation and latency.

    PubMed

    Yarom, N; Buchner, A; Dayan, D

    2005-01-01

    Oro-facial manifestations of herpes simplex virus (HSV) infections are very common, and include primary herpetic gingivo-stomatitis, recurrent herpes labialis and recurrent intra-oral herpes. Recent research in molecular biology has advanced our knowledge of the HSV pathogenesis and behavior. Understanding the exact mechanism of HSV latency and reactivation enables improvement of drug therapy and prevention strategies of HSV infections. The aim of this review is to update the recent development in the biological and clinical research related to HSV infection, focusing on oral and perioral lesions. PMID:15786655

  19. Herpes simplex virus 2 infection: molecular association with HIV and novel microbicides to prevent disease.

    PubMed

    Suazo, Paula A; Tognarelli, Eduardo I; Kalergis, Alexis M; González, Pablo A

    2015-04-01

    Infection with herpes simplex viruses is one of the most ancient diseases described to affect humans. Infection with these viruses produces vexing effects to the host, which frequently recur. Infection with herpes simplex viruses is lifelong, and currently there is no vaccine or drug to prevent or cure infection. Prevalence of herpes simplex virus 2 (HSV-2) infection varies significantly depending on the geographical region and nears 20% worldwide. Importantly, HSV-2 is the first cause of genital ulcers in the planet. HSV-2 affects approximately 500 million people around the globe and significantly increases the likelihood of acquiring the human immunodeficiency virus (HIV), as well as its shedding. Thus, controlling HSV-2 infection and spread is of public health concern. Here, we review the diseases produced by herpes simplex viruses, the factors that modulate HSV-2 infection, the relationship between HSV-2 and HIV and novel therapeutic and prophylactic microbicides/antivirals under development to prevent infection and pathological outcomes produced by this virus. We also review mutations associated with HSV-2 resistance to common antivirals. PMID:25209142

  20. Herpes simplex colitis in a child with combined liver and small bowel transplant.

    PubMed

    Delis, S; Kato, T; Ruiz, P; Mittal, N; Babinski, L; Tzakis, A

    2001-10-01

    Herpes simplex virus (HSV) has been a rare cause of gastrointestinal (GI) infection, especially in immunocompromised patients. A variety of GI sites may be involved; however, only three reported cases of HSV colitis have been documented in the literature. To our knowledge, this is the first report of HSV colitis in a small bowel transplant recipient. PMID:11560759

  1. Herpes simplex virus (HSV) colitis in a bone marrow transplant recipient.

    PubMed

    Naik, H R; Chandrasekar, P H

    1996-02-01

    Herpes simplex virus (HSV) infections are common in bone marrow transplantation patients. Unusual sites may be involved, however colonic disease with HSV is rare. We report a successfully treated case of colitis due to HSV, cytomegalovirus, Clostridium difficile and graft-versus-host disease in an allogeneic marrow recipient. PMID:8640181

  2. Herpes simplex virus lymphadenitis: case report and review of the literature.

    PubMed

    Witt, Mallory D; Torno, Mauro S; Sun, Nora; Stein, Tomiko

    2002-01-01

    Localized or regional necrotizing lymphadenitis is an extremely uncommon manifestation of herpes simplex virus (HSV) infection. We report a case of necrotizing HSV lymphadenitis in a patient with both common variable immunodeficiency and natural killer cell deficiency and review the literature on this unusual complication of HSV infection. PMID:11731938

  3. Intraoral herpes simplex virus infection in a patient with common variable immunodeficiency.

    PubMed

    Villa, Alessandro; Treister, Nathaniel S

    2013-10-01

    We report a challenging case of an atypical presentation of recrudescent herpes simplex virus infection in a patient with common variable immunodeficiency. Oral infections in immunosuppressed patients may present with unusual clinical features that can mimic non-infectious diseases. This report discusses the diagnostic steps necessary for definitive diagnosis and to guide appropriate and effective management. PMID:23933299

  4. 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:…

  5. 75 FR 59611 - Microbiology Devices; Reclassification of Herpes Simplex Virus Types 1 and 2 Serological Assays...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... final rule that appeared in the Federal Register of August 25, 2009 (74 FR 42773). The direct final rule... INFORMATION: In the Federal Register of August 25, 2009 (74 FR 42773), FDA solicited comments concerning the... Herpes Simplex Virus Types 1 and 2 Serological Assays; Confirmation of Effective Date AGENCY: Food...

  6. Molluscum contagiosum and herpes simplex in Maasai pastoralists; refeeding activation of virus infection following famine?

    PubMed

    Murray, M J; Murray, A B; Murray, N J; Murray, M B; Murray, C J

    1980-01-01

    An epidemic of molluscum contagiosum and oro-genital herpes simplex was observed in Maasai pastoralists of the Rift Valley. It coincided with a period of refeeding following famine, when the relief diet was different from normal milk fare. We propose that refeeding may be an important mechanism for activation of certain viral infections previously suppressed by famine. PMID:7434431

  7. Acute retinal necrosis secondary to herpes simplex virus type 2 with preexisting chorioretinal scarring.

    PubMed

    Moesen, Ingemarie; Khemka, Sneh; Ayliffe, William

    2008-01-01

    Acute retinal necrosis in children is a devastating disease that requires early diagnosis and treatment. The authors describe a rarely reported case of bilateral acute retinal necrosis in a child caused by neonatal herpes simplex virus type 2, where the presence of previous chorioretinal scarring made diagnosis challenging. PMID:18286969

  8. Quantitative autoradiographic mapping of focal herpes simplex virus encephalitis using a radiolabeled antiviral drug

    SciTech Connect

    Price, R.

    1984-12-18

    A method of mapping herpes simplex viral infection comprising administering a radiolabeled antiviral active 5-substituted 1-(2'-deoxy-2'-substituted-D-arabinofuranosyl) pyrimidine nucleoside to the infected subject, and scanning the area in which the infection is to be mapped for the radiolabel.

  9. Amino-terminal sequence of glycoprotein D of herpes simplex virus types 1 and 2

    SciTech Connect

    Eisenberg, R.J.; Long, D.; Hogue-Angeletti, R.; Cohen, G.H.

    1984-01-01

    Glycoprotein D (gD) of herpes simplex virus is a structural component of the virion envelope which stimulates production of high titers of herpes simplex virus type-common neutralizing antibody. The authors caried out automated N-terminal amino acid sequencing studies on radiolabeled preparations of gD-1 (gD of herpes simplex virus type 1) and gD-2 (gD of herpes simplex virus type 2). Although some differences were noted, particularly in the methionine and alanine profiles for gD-1 and gD-2, the amino acid sequence of a number of the first 30 residues of the amino terminus of gD-1 and gD-2 appears to be quite similar. For both proteins, the first residue is a lysine. When we compared out sequence data for gD-1 with those predicted by nucleic acid sequencing, the two sequences could be aligned (with one exception) starting at residue 26 (lysine) of the predicted sequence. Thus, the first 25 amino acids of the predicted sequence are absent from the polypeptides isolated from infected cells.

  10. Influence of herpes simplex virus infection on benzo(a)pyrene metabolism in monkey kidney cells

    SciTech Connect

    Degenhardt, J.H.; Whitcomb, B.; Hall, M.R.

    1984-01-01

    Current research in our laboratory is designed to investigate the intracellular interactions of BP with oncogenic DNA viruses of animals and humans. In this study, our purpose was to determine whether BP is metabolized in herpes simplex virus type 2 (HSV-2) infected cells and whether HSV-2 infection affects intracellular levels of the aryl hydrocarbon hydroxylase system necessary for BP metabolism.

  11. 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.

  12. 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

  13. 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

  14. Anti-herpes simplex virus activity of polysaccharides from Eucheuma gelatinae.

    PubMed

    Jin, Fujun; Zhuo, Cuiqin; He, Zhe; Wang, Huailin; Liu, Wei; Zhang, Rong; Wang, Yifei

    2015-03-01

    Acyclovir is a commonly-used drug for treating herpes simplex virus (HSV) infections, but with its wide clinical application, more and more resistant strains have been found. Therefore, seeking a drug that can act against acyclovir-resistant virus has become an important goal of drug screening and development. In this study, plaque reduction assay, real-time PCR, Western blot, and immunofluorescence technique were used to investigate the antiviral effect of Eucheuma gelatinae polysaccharide (EGP) on HSV and to preliminarily clarify the in vitro anti-HSV mechanism of EGP. EGP was found to significantly inhibit HSV infection in vitro and displayed a good inhibitory effect on acyclovir-resistant strains. More detailed experiments have shown that EGP prevented early HSV-1 infection through directly inactivating HSV-1 particles and impairing virus attachment, but without effect on viral penetration. EGP also inhibited the RNA synthesis of HSV-1 early gene and late gene as well as viral DNA replication; no effect on immediate-early gene synthesis was observed. Besides, through immunofluorescence and western blot, we found that EGP significantly affected the protein synthesis of HSV-1. Taken together, these results demonstrate that EGP exerts its anti-HSV activity mainly through impeding early HSV-1 infection and inhibiting viral RNA and DNA syntheses. The weak cytotoxicity, strong viral inactivation as well as attachment inhibition activity enable EGP to be a virucide candidate for HSV therapy, especially for drug-resistant strains. PMID:25604263

  15. A DNA Fragment of Herpes Simplex 2 and Its Transcription in Human Cervical Cancer Tissue

    PubMed Central

    Frenkel, Niza; Roizman, Bernard; Cassai, Enzo; Nahmias, Andre

    1972-01-01

    A human cervical tumor, free of detectable infectious herpes simplex 2 virus, contained a fragment comprising 39% of herpes viral DNA. Renaturation kinetics indicate that an average of 1 to 3.5 DNA fragments of herpes simplex virus are present per cell, depending on the ploidy of the cells in this particular tumor. Virus-specific sequences were found linked to highly repetitive sequences of host DNA, which reassociated under conditions designed to preclude reassociation of viral sequences. The tumor also contained RNA transcripts complementary to 5% of the viral DNA. The fraction of viral DNA template transcribed in the cervical tumor is considerably less than that transcribed in productively infected cells (50%). PMID:4345508

  16. Fatal herpes simplex infection in a pygmy African hedgehog (Atelerix albiventris).

    PubMed

    Allison, N; Chang, T C; Steele, K E; Hilliard, J K

    2002-01-01

    An adult pygmy African hedgehog developed acute posterior paresis attributed to a prolapsed intervertebral disc diagnosed by C-T scan. Corticosteroid therapy resulted in prompt resolution of the ataxia, but 2 weeks later the animal became anorexic and died. Macroscopically, the liver was stippled with punctate off-white foci which were confirmed microscopically to be foci of necrosis. Numerous hepatocytes contained intranuclear inclusions and syncytial cell formation was also present. A herpes virus was isolated and identified by fluorescent antibody and polymerase chain reaction studies as herpesvirus simplex type 1. To our knowledge, this is the first report of herpes infection in the African hedgehog and the first time herpes simplex has been identified as a cause of disease in insectivores. PMID:11814325

  17. Activity investigation of pinostrobin towards herpes simplex virus-1 as determined by atomic force microscopy.

    PubMed

    Wu, Nan; Kong, Yu; Zu, Yuangang; Fu, Yujie; Liu, Zhiguo; Meng, Ronghua; Liu, Xia; Efferth, Thomas

    2011-01-15

    In the present study, the antiviral activity of pinostrobin towards herpes simplex virus-1 (HSV-1) was investigated by MTT assay and atomic force microscopy. Pinostrobin can inhibit HSV-1 replication with 50% effective concentration (EC(50)) of 22.71 ± 1.72 μg/ml. MTT assay showed HSV-1 was significantly inhibited when pretreated with pinostrobin, with the inhibition of 85.69 ± 2.59%. Significant changes in morphology and size of HSV-1 were observed by atomic force microscopy (AFM) in response to pinostrobin treatment. AFM topography and phase images showed that with increasing time, the envelope was shedded and damaged, finally leading to virus inactivation. With increasing concentration, pinostrobin caused a gradual leakage, also contributing to breakage of the envelope and virus inactivation. Treatment effect of oral pinostrobin in vivo showed that pinostrobin (50mg/kg/dose) possesses definite therapeutical effect in the development of lesion score. In general, the results showed that AFM represents a powerful technique for the investigation of morphology and size of HSV-1 treated by antiviral agents. AFM is applicable to study chemically induced morphological changes at the nanometer level. PMID:20739162

  18. Non-traumatic acquisition of herpes simplex virus infection through the eye.

    PubMed Central

    Kaye, S B; Shimeld, C; Grinfeld, E; Maitland, N J; Hill, T J; Easty, D L

    1992-01-01

    Primary ocular herpes is usually seen as a follicular conjunctivitis and blepharitis, with or without involvement of the cornea. It is unknown, however, to what extent asymptomatic and/or subclinical primary disease occurs, and whether primary ocular herpes follows direct droplet spread to the eye. Previous models of murine ocular herpes have used trauma (scarification) to introduce virus into the cornea, producing disease which results in significant corneal scarring. To mimic a likely route of infection in humans, a droplet containing virus was placed on the mouse eye and clinical disease recorded. At least 1 month after inoculation, serum was assayed for neutralising antibodies and the cornea, iris, and trigeminal ganglion were investigated for evidence of herpes simplex virus type 1, by cocultivation and the polymerase chain reaction. Some animals showed a severe ulcerative blepharitis with little to no involvement of the cornea, while disease was undetectable in others. The development of disease depended on the dose and strain of virus and age of the animal, with older mice appearing more resistant. Virus was isolated from the trigeminal ganglion of younger animals inoculated with higher doses of virus, after 21 days in culture, suggesting that latency had been established. Neutralising antibodies were present in most mice irrespective of the presence of recognisable clinical disease. Using primers for the thymidine kinase and glycoprotein C regions of the viral genome, herpes simplex virus type 1 DNA was found in the cornea, iris, and trigeminal ganglion of most animals and showed a good correlation with the presence of neutralising antibodies. It would thus appear that herpes simplex virus type 1 is able to accede into the cornea, iris, and trigeminal ganglion following nontraumatic application of virus onto the mouse eye. This model mimics primary ocular disease in humans and may be useful for studies on recurrent disease and the spread of ocular herpes

  19. Herpes Simplex Virus Sepsis in a Young Woman with Crohn's Disease.

    PubMed

    Haag, Lea-Maxie; Hofmann, Jörg; Kredel, Lea Isabell; Holzem, Christina; Kühl, Anja A; Taube, Eliane T; Schubert, Stefan; Siegmund, Britta; Epple, Hans-Jörg

    2015-12-01

    We present the case of a herpes simplex virus-1 [HSV-1] sepsis with severe herpes hepatitis in a young female treated with triple immunosuppressive therapy [adalimumab, azathioprine, prednisolone] for refractory Crohn's disease [CD]. The patient presented with high fever, generalised abdominal tenderness, strongly elevated transaminases, coagulopathy, and pancytopenia. Comprehensive diagnostics including blood HSV-1 polymerase chain reaction [PCR], liver biopsy, and immunohistochemistry revealed the diagnosis of fulminant herpes hepatitis. HSV-1 positivity of cutaneous lesions proved the disseminated nature of the infection. Early treatment with intravenous acyclovir led to a rapid improvement of the patient's condition and resulted in a full recovery of her liver function. This is the first reported case of HSV-sepsis in a patient with CD. Physicians treating inflammatory bowel disease [IBD] patients with combined immunosuppressive therapy should be aware of the possibility of herpes hepatitis, and early empirical antiviral therapy should be considered in immunosuppressed patients presenting with fever and severe anicteric hepatitis. PMID:26351382

  20. New concepts in herpes simplex virus vaccine development: notes from the battlefield

    PubMed Central

    Dasgupta, Gargi; Chentoufi, Aziz A; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

    2009-01-01

    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. PMID:19627185

  1. [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. PMID:12688217

  2. Effect of Prior Immunization on Induction of Cervical Cancer in Mice by Herpes Simplex Virus Type 2

    NASA Astrophysics Data System (ADS)

    Budd Wentz, W.; Heggie, Alfred D.; Anthony, Donald D.; Reagan, James W.

    1983-12-01

    Previous studies at this laboratory showed that repeated application of inactivated herpes simplex virus type 2 to the mouse cervix produces premalignant and malignant lesions. In the present study mice were inoculated with inactivated herpes simplex virus type 2 or control solution and Freund's adjuvant by intraperitoneal and subcutaneous routes before exposure of the cervix to inactivated virus. It appears that immunization with inactivated virus conferred a protection against the induction of cervical carcinoma.

  3. 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

  4. Replication of herpes simplex virus DNA: localization of replication recognition signals within defective virus genomes.

    PubMed Central

    Vlazny, D A; Frenkel, N

    1981-01-01

    Serially passaged herpes simplex virus type 1 (HSV-1) strain Justin was previously shown to contain defective virus genomes consisting of head-to-tail reiterations of sequences derived from the end of the S component of the standard virus DNA. Cotransfection of purified monomeric defective genome repeat units with foster helper virus DNAs onto rabbit skin cells resulted in regeneration and replication of concatemeric defective DNA molecules which were successfully encapsidated. Thus, defective HSV-1 (Justin) genomes contain, within their limited DNA sequences, a sufficient set of recognition sites required for HSV DNA replication and packaging. The arrangement of repeat units within the regenerated defective virus genomes was consistent with their replication by a rolling circle mechanism in which a single repeat unit served as the circularized template. This replication occurred most actively late after infection and could be shown to be inhibited by low concentrations of phosphonoacetate known to inhibit the HSV-specified viral DNA polymerase selectively. The resultant concatemers were shown to be cleaved to Mr 100 X 10(6) DNA molecules which were terminated at one end with the proper ac end sequence of the parental standard virus DNA. Images PMID:6262768

  5. Genetic studies of cell fusion induced by herpes simplex virus type 1

    SciTech Connect

    Read, G.S.; Person, S.; Keller, P.M.

    1980-07-01

    Eight cell fusion-causing syn mutants were isolated from the KOS strain of herpes simplex virus type 1. Unlike the wild-type virus, the mutants produced plaques containing multinucleated cells, or syncytia. Fusion kinetics curves were established with a Coulter Counter assay for the mutants and wild-type virus in single infections of human embryonic lung (HEL) cells, for the mutants and wild-type virus in mixed infections (dominance test), and for pairs of mutants in mixed infection and proceeded with an exponential decrease in the number of small single cells. At some later time that was characteristic of the mutant, there was a significant reduction in the rate of fusion for all but possibly one of the mutants. Although the wild-type virus did not produce syncytial plaques, it did induce a small amount of fusion that stopped abruptly about 2 h after it started. These data are consistent with the hypothesis that both mutants and wild type induce an active fusion inducer and that the activity of this inducer is subsequently inhibited. The extent of fusion is apparently determined by the length of the interval during which the fusion inducer is active. That fusion is actively inhibited in wild-type infections is indicated by the observation that syn mutant-infected cells fused more readily with uninfected cells than with wild type-infected cells.

  6. The adeno-associated virus rep gene suppresses herpes simplex virus-induced DNA amplification.

    PubMed Central

    Heilbronn, R; Bürkle, A; Stephan, S; zur Hausen, H

    1990-01-01

    Herpes simplex virus (HSV) induces within the host cell genome DNA amplification which can be suppressed by coinfection with adeno-associated virus (AAV). To characterize the AAV functions mediating this effect, cloned AAV type 2 wild-type or mutant genomes were transfected into simian virus 40 (SV40)-transformed hamster cells together with the six HSV replication genes (encoding UL5, UL8, major DNA-binding protein, DNA polymerase, UL42, and UL52) which together are necessary and sufficient for the induction of SV40 DNA amplification (R. Heilbronn and H. zur Hausen, J. Virol. 63:3683-3692, 1989). The AAV rep gene was identified as being responsible for the complete inhibition of HSV-induced SV40 DNA amplification. Likewise, rep inhibited origin-dependent HSV replication. rep neither killed the transfected host cells nor interfered with gene expression from the cotransfected amplification genes. This points to a specific interference with HSV-induced DNA amplification. Images PMID:2159559

  7. Identification of a herpes simplex virus function that represses late gene expression from parental viral genomes.

    PubMed Central

    Godowski, P J; Knipe, D M

    1985-01-01

    The expression of herpes simplex virus gamma 2 (late) genes is inhibited before the onset of viral DNA replication. We report that the block in the expression of certain gamma 2 genes is relieved, at least in part, by defects in the beta ICP8 protein. We have examined the expression of the gamma 2 gene encoding glycoprotein C (gC) in cells infected with a temperature-sensitive ICP8 mutant. Under conditions in which viral DNA replication is inhibited, cells infected with the ICP8 mutant overproduce the gC family of mRNAs relative to the level observed in cells infected with a wild-type virus. The gC mRNA synthesized in cells infected with the ICP8 mutant virus is correctly initiated and spliced and is translated with the same relative efficiency as in cells infected with a replicating wild-type virus. These results suggest that ICP8 is involved in the negative regulation of gamma 2 genes expressed from parental viral genomes. The level of gC expression was greatest in cells infected with a replicating wild-type virus. These data suggest that DNA replication and genome amplification are not absolute requirements for gamma 2 gene expression but may facilitate full-level expression of these genes. Images PMID:2991561

  8. In vitro and in vivo antiviral activity of scopadulcic acid B from Scoparia dulcis, Scrophulariaceae, against herpes simplex virus type 1.

    PubMed

    Hayashi, K; Niwayama, S; Hayashi, T; Nago, R; Ochiai, H; Morita, N

    1988-09-01

    The antiviral activity of five diterpenoids isolated from Scoparia dulcis L., Scrophulariaceae, was examined in vitro against herpes simplex virus type 1. Among these compounds, only scopadulcic acid B was found to inhibit the viral replication with the in vitro therapeutic index of 16.7. The action of scopadulcic acid B was not due to a direct virucidal effect or inhibition of virus attachment to host cells. Single-cycle replication experiments indicated that the compound interfered with considerably early events of virus growth. The influence of scopadulcic acid B on the course of the primary corneal herpes simplex virus infection was investigated by means of a hamster test model. When the treatment was initiated immediately after virus inoculation, scopadulcic acid B, when applied orally or intraperitoneally, effectively prolonged both the appearance of herpetic lesions and the survival time at the dose of 100 and 200 mg/kg per day. PMID:2852487

  9. Herpes simplex Virus Esophagitis in an Immunocompetent Patient with Ebstein-Barr Virus Infection.

    PubMed

    Tzouvala, M; Gaglia, A; Papantoniou, N; Triantafyllou, K; Karamanolis, G

    2008-09-01

    Epstein-Barr virus infectious mononucleosis can cause transient immune deficiency which may predispose to reactivation of latent herpes simplex virus (HSV) infection in the immunocompetent host. We report the case of a 15-year-old male who presented with severe odynophagia and herpes labialis during the course of Epstein-Barr virus infectious mononucleosis that had been diagnosed ten days before. Esophagoscopy revealed extensive ulcerations with distinct borders and whitish exudates at the mid and distal esophagus. Polymerase chain reaction detected HSV-1 DNA in the biopsy specimens. The patient was treated with intravenous acyclovir. The symptoms resolved rapidly within 3 days, in accordance with improved endoscopic findings. PMID:21897798

  10. 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.

  11. Identification of TRIM27 as a Novel Degradation Target of Herpes Simplex Virus 1 ICP0

    PubMed Central

    Conwell, Sara E.; White, Anne E.; Harper, J. Wade

    2014-01-01

    ABSTRACT The herpes simplex virus 1 (HSV-1) immediate early protein ICP0 performs many functions during infection, including transactivation of viral gene expression, suppression of innate immune responses, and modification and eviction of histones from viral chromatin. Although these functions of ICP0 have been characterized, the detailed mechanisms underlying ICP0's complex role during infection warrant further investigation. We thus undertook an unbiased proteomic approach to identifying viral and cellular proteins that interact with ICP0 in the infected cell. Cellular candidates resulting from our analysis included the ubiquitin-specific protease USP7, the transcriptional repressor TRIM27, DNA repair proteins NBN and MRE11A, regulators of apoptosis, including BIRC6, and the proteasome. We also identified two HSV-1 early proteins involved in nucleotide metabolism, UL39 and UL50, as novel candidate interactors of ICP0. Because TRIM27 was the most statistically significant cellular candidate, we investigated the relationship between TRIM27 and ICP0. We observed rapid, ICP0-dependent loss of TRIM27 during HSV-1 infection. TRIM27 protein levels were restored by disrupting the RING domain of ICP0 or by inhibiting the proteasome, arguing that TRIM27 is a novel degradation target of ICP0. A mutant ICP0 lacking E3 ligase activity interacted with endogenous TRIM27 during infection as demonstrated by reciprocal coimmunoprecipitation and supported by immunofluorescence data. Surprisingly, ICP0-null mutant virus yields decreased upon TRIM27 depletion, arguing that TRIM27 has a positive effect on infection despite being targeted for degradation. These results illustrate a complex interaction between TRIM27 and viral infection with potential positive or negative effects of TRIM27 on HSV under different infection conditions. IMPORTANCE During productive infection, a virus must simultaneously redirect multiple cellular pathways to replicate itself while evading detection by the

  12. Herpes Simplex Virus: Genome Size and Redundancy Studied by Renaturation Kinetics

    PubMed Central

    Frenkel, Niza; Roizman, Bernard

    1971-01-01

    Herpes simplex virus subtype 1 deoxyribonucleic acid (DNA) was sheared in a French press to uniform fragments, denatured by heating, then allowed to reassociate. The renaturation reaction followed second-order kinetics with a single rate constant indicating that at least 95% of the genome was unique and that repetitive sequences, if present, were not detectable by this technique. The kinetic complexity of the herpes simplex genome was determined by DNA renaturation kinetics to be (95 ± 1) × 106 daltons. Since this value is in excellent agreement with the molecular weight of viral DNA [(99 ± 5) × 106 daltons] obtained from velocity sedimentation studies, it is concluded that virions contain only one species of double-stranded DNA molecules 95 × 106 to 99 × 106 daltons in molecular weight. PMID:4331657

  13. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells

    SciTech Connect

    Redfield, D.C.; Richman, D.D.; Oxman, M.N.; Kronenberg, L.H.

    1981-06-01

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays.

  14. Targeted Entry of Enveloped Viruses: Measles and Herpes Simplex Virus I

    PubMed Central

    Navaratnarajah, Chanakha K.; Miest, Tanner S.; Carfi, Andrea; Cattaneo, Roberto

    2011-01-01

    We compare the receptor-based mechanisms that a small RNA virus and a larger DNA virus have evolved to drive the fusion of viral and cellular membranes. Both systems rely on tight control over triggering the concerted refolding of a trimeric fusion protein. While measles virus entry depends on a receptor-binding protein and a fusion protein only, the herpes simplex virus is more complex and requires four viral proteins. Nevertheless, in both viruses a receptor-binding protein is required for triggering the membrane fusion process. Moreover, specificity domains can be appended to these receptor-binding proteins to target virus entry to cells expressing a designated receptor. We discuss how principles established with measles and herpes simplex virus can be applied to targeting other enveloped viruses, and alternatively how retargeted envelopes can be fitted on foreign capsids. PMID:22440965

  15. Herpes simplex virus type 1 entry into epithelial MDCKII cells: role of VASP activities.

    PubMed

    Jaeger, Verena; Hoppe, Sven; Petermann, Philipp; Liebig, Timo; Jansen, Matthias K; Renné, Thomas; Knebel-Mörsdorf, Dagmar

    2010-09-01

    VASP is an actin-regulatory protein that links signalling to remodelling of the cytoskeleton. We investigated the role of VASP during entry of herpes simplex viruses into epithelial MDCKII cells. As VASP functions are regulated by phosphorylations, the phosphorylation pattern was determined upon infection. Phosphorylated VASP decreased temporarily at 15 and 30 min after infection. The impact of phosphorylated VASP was addressed by overexpression of phosphomimetic VASP mutants. Our results revealed that phosphorylated VASP slightly reduced the number of infected cells. Expression studies with deletion mutants further indicated minor effects of VASP on infection efficiency, whereas RNA interference studies demonstrated that reduced VASP expression did not suppress infection. We conclude that VASP activities alone may contribute to herpes simplex virus infection to only a minor extent. PMID:20463151

  16. Which plant for which skin disease? Part 1: Atopic dermatitis, psoriasis, acne, condyloma and herpes simplex.

    PubMed

    Reuter, Juliane; Wölfle, Ute; Weckesser, Steffi; Schempp, Christoph

    2010-10-01

    Plant extracts and isolated compounds are increasingly used in cosmetics and food supplements to improve skin conditions. We first introduce the positive plant monographs with dermatological relevance of the former German Commission E. Subsequently clinical studies with botanicals for atopic dermatitis, psoriasis, acne, condylomata acuminata and herpes simplex are discussed. The best studies have been conducted with atopic dermatitis and psoriasis patients. Mahonia aquifolium, Hypericum perforatum, Glycyrrhiza glabra and certain traditional Chinese therapies have been shown to be effective in the treatment of atopic dermatitis. Mahonia aquifolium, Indigo naturalis and Capsicum frutescens are effective treatments for psoriasis. Green tea extract and tea tree oil have been investigated in the treatment of acne. Podophyllin and green tea extract are effective treatments for condylomata acuminata. Balm mint and a combination of sage and rhubarb have been shown to be effective in the treatment of herpes simplex in proof of concept studies. PMID:20707875

  17. Pathogenesis of herpes simplex labialis: correlation of vesicle fluid interferon with lesion age and virus titer.

    PubMed Central

    Spruance, S L; Green, J A; Chiu, G; Yeh, T J; Wenerstrom, G; Overall, J C

    1982-01-01

    Of 51 patients with herpes simplex labialis, 50 had detectable interferon (IFN) in samples of lesion vesicle fluid. The median titer of vesicle fluid IFN was 8,200 U. and the range of values was 400 to 63,600 U. The amount of vesicle fluid IFN was correlated with lesion age (r = 0.32, P = 0.024) and vesicle fluid virus titer (r = 0.59, P = 0.00004), but not with the clinical severity of the disease. The presence of vesicle fluid IFN (1,500 to 28,600 U) in 15 lesions less than 12 h old emphasizes the need for early treatment in studies of antiviral agents for herpes simplex labialis. PMID:6178690

  18. Rapid isolation of herpes simplex virus by using mink lung and rhabdomyosarcoma cell cultures.

    PubMed Central

    Johnston, S L; Wellens, K; Siegel, C S

    1990-01-01

    Highly sensitive and rapid results can be obtained by isolating herpes simplex virus from clinical specimens in simple cell culture with rhabdomyosarcoma (RD) cells. In this study, 3,186 clinical specimens were inoculated into locally produced, equivalent-age RD and mink lung (ML) cells. Of 727 positive isolates, all (100%) were isolated from RD cells and only 691 (95%) were isolated from ML cells. Furthermore, 162 of the positive isolates (22%) were isolated in RD cells earlier than in ML cells. RD cells are continuous and can be cultivated in house without decreasing sensitivity as the passage number increases. They produce a highly distinguishable cytopathic effect in response to herpes simplex virus and maintain intense confirmatory staining patterns. PMID:2177754

  19. Herpes simplex virus type 1 infection in two pet marmosets in Japan.

    PubMed

    Imura, Kei; Chambers, James Kenn; Uchida, Kazuyuki; Nomura, Shunsuke; Suzuki, Satoshi; Nakayama, Hiroyuki; Miwa, Yasutsugu

    2014-12-01

    An 8-month-old common marmoset (Callithrix jacchus) was presented with tic-like symptoms, and a 2-year-old pigmy marmoset (Callithrix pygmaea) was presented with dyspnea and hypersalivation. Both monkeys died within a few days, and necropsies were performed. Histopathological examinations revealed ulcerative stomatitis with epithelial cell swelling and eosinophilic intranuclear inclusion bodies in the oral epithelium of both cases. In the central and peripheral nervous systems, neuronal cell degeneration with intranuclear inclusion bodies was observed. Immunohistochemical examination using anti-herpes simplex virus type 1 antibody revealed virus antigens in both cases. Both animals had been kept as pets with limited exposure to the ambient environment except via their owners. Therefore, herpes simplex virus type-1 was probably acquired from close contact with their owners. PMID:25649955

  20. Herpes Simplex Virus Type 1 Infection in Two Pet Marmosets in Japan

    PubMed Central

    IMURA, Kei; CHAMBERS, James Kenn; UCHIDA, Kazuyuki; NOMURA, Shunsuke; SUZUKI, Satoshi; NAKAYAMA, Hiroyuki; MIWA, Yasutsugu

    2014-01-01

    An 8-month-old common marmoset (Callithrix jacchus) was presented with tic-like symptoms, and a 2-year-old pigmy marmoset (Callithrix pygmaea) was presented with dyspnea and hypersalivation. Both monkeys died within a few days, and necropsies were performed. Histopathological examinations revealed ulcerative stomatitis with epithelial cell swelling and eosinophilic intranuclear inclusion bodies in the oral epithelium of both cases. In the central and peripheral nervous systems, neuronal cell degeneration with intranuclear inclusion bodies was observed. Immunohistochemical examination using anti-herpes simplex virus type 1 antibody revealed virus antigens in both cases. Both animals had been kept as pets with limited exposure to the ambient environment except via their owners. Therefore, herpes simplex virus type-1 was probably acquired from close contact with their owners. PMID:25649955

  1. Herpes simplex virus-mediated human hypoxanthine-guanine phosphoribosyltransferase gene transfer into neuronal cells

    SciTech Connect

    Palella, T.D.; Silverman, L.J.; Schroll, C.T.; Homa, F.L.; Levine, M.; Kelley, W.N.

    1988-01-01

    The virtually complete deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a devastating neurological disease, Lesch-Nyhan syndrome. Transfer of the HPRT gene into fibroblasts and lymphoblasts in vitro and into hematopoietic cells in vivo has been accomplished by other groups with retroviral-derived vectors. It appears to be necessary, however, to transfer the HPRT gene into neuronal cells to correct the neurological dysfunction of this disorder. The neurotropic virus herpes simplex virus type 1 has features that make it suitable for use as a vector to transfer the HPRT gene into neuronal tissue. This report describes the isolation of an HPRT-deficient rat neuroma cell line, designated B103-4C, and the construction of a recombinant herpes simplex virus type 1 that contained human HPRT cDNA. These recombinant viruses were used to infect B103-4C cells. Infected cells expressed HPRT activity which was human in origin.

  2. 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.

  3. 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. PMID:25535792

  4. 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 ...

  5. Topical and systemic therapies for oral and perioral herpes simplex virus infections.

    PubMed

    Stoopler, Eric T; Balasubramaniam, Ramesh

    2013-04-01

    Oral and perioral herpes simplex virus (HSV) infections in healthy individuals often present with signs and symptoms that are clearly recognized by oral health care providers (OHCPs). Management of these infections is dependent upon a variety of factors and several agents may be used for treatment to accelerate healing and decrease symptoms associated with lesions. This article will review the pertinent aspects of topical and systemic therapies of HSV infections for the OHCP. PMID:23705241

  6. Vessel wall enhancement in herpes simplex virus central nervous system vasculitis.

    PubMed

    Guerrero, Waldo R; Dababneh, Haitham; Hedna, Shushrutha; Johnson, James A; Peters, Keith; Waters, Michael F

    2013-09-01

    Infection is a well-known cause of cerebral vasculopathy and vasculitis. We report a 36-year-old woman with cerebral vasculitis and ischemic stroke secondary to herpes simplex virus (HSV). MRI studies revealed a pontine stroke with basilar artery stenosis and vessel wall gadolinium enhancement. This case demonstrates the ability of HSV to cause a focal brainstem vasculitis and the utility of enhanced MRI in the diagnosis of stroke related to HSV central nervous system vasculitis. PMID:23517674

  7. Multiple strokes associated with herpes simplex virus type-2 infection: case report.

    PubMed

    Joshi, Prajwol

    2016-04-01

    Herpes simplex virus (HSV) type-2 is known to cause meningitis and usually runs a benign course. Association of such infection with vasculitis of the central nervous system is not well known. Presented here is a case initially diagnosed as aseptic meningitis that subsequently evolved as stroke and exhibited angiographic evidence of widespread vasculitis of the intracranial vessels in association with a positive polymerase chain reaction (PCR) for HSV-2 in the cerebrospinal fluid (CSF). PMID:26443565

  8. Slipping and Sliding: frameshift mutations in herpes simplex virus thymidine kinase and drug-resistance

    PubMed Central

    Griffiths, Anthony

    2011-01-01

    Some of the most successful antiviral agents currently available are effective against herpes simplex virus. However, resistance to these drugs is frequently associated with significant morbidity, particularly in immunocompromised patients. In addition to the clinical implications of drug resistance, the range of biological processes exploited by the virus to attain resistance while maintaining pathogenicity is proving to be surprising. These mechanisms, which include ribosomal frameshifting, induced infidelity of the DNA polymerase, and internal ribosome entry, are discussed. PMID:21940196

  9. Proton MR spectroscopy in herpes simplex encephalitis: Assessment of neuronal loss

    SciTech Connect

    Menon, D.K.; Sargentoni, J.; Peden, C.J.; Bell, J.D.; Cox, I.J.; Coutts, G.A.; Baudouin, C.; Newman, C.G. )

    1990-05-01

    We present here the case of an 11-year-old boy with herpes simplex encephalitis diagnosed on the basis of clinical features, serology, and response to acyclovir, who relapsed after 3 weeks of therapy. In vivo proton magnetic resonance spectroscopy (1H MRS) of the brain, at 8 and 16 weeks after the onset of symptoms, showed abnormalities, most prominently a reduction in the N-acetylaspartate/choline ratio. The role of 1H MRS in assessing disease activity is discussed.

  10. In vitro activity of extracts of Persea americana leaves on acyclovir-resistant and phosphonoacetic resistant Herpes simplex virus.

    PubMed

    Miranda, M M; Almeida, A P; Costa, S S; Santos, M G; Lagrota, M H; Wigg, M D

    1997-12-01

    The lyophilized aqueous crude extract (LACE) from leaves of Persea americana (Lauraceae) species showed a strong inhibitory effect on acyclovir (ACG(r)4 and dlsp TK mutants) and PAA-resistant (PAA(r)5 mutant) herpes simplex virus. After exhaustive washing of LACE using methanol, the soluble fraction was chromatographed on a reverse-phase column giving 11 fractions that were revealed by thin-layer chromatography. Analysis of the antiviral effect of the fractions showed the extract contained compounds that were able to inhibit extracellular virus and the replication of resistant acyclovir HSV. The virucidal effect was concentrated from fraction 4 up to 8. Fraction 7 mainly contains the flavonoid isoquercitrin, and fraction 8 the flavonoid quercitrin. The flavonoid afzelin that is the major substance present in the fraction 9 showed virustatic effect with no virucidal effect. These results show P. americana is a potential plant extract for treatment of herpes simplex virus infections either alone or associated with acyclovir. PMID:23195586

  11. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

    SciTech Connect

    Pei, Ying; Chen, Zhen-Ping; Ju, Huai-Qiang; Komatsu, Masaaki; Ji, Yu-hua; Liu, Ge; Guo, Chao-wan; Zhang, Ying-Jun; Yang, Chong-Ren; Wang, Yi-Fei; Kitazato, Kaio

    2011-02-11

    Research highlights: {yields} We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. {yields} Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. {yields} Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7{sup -/-} cells (autophagy-defective cells) derived from an atg7{sup -/-} knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

  12. Transient fasting enhances replication of oncolytic herpes simplex virus in glioblastoma.

    PubMed

    Esaki, Shinichi; Rabkin, Samuel D; Martuza, Robert L; Wakimoto, Hiroaki

    2016-01-01

    Short-term nutritional restriction (fasting) has been shown to enhance the efficacy of chemotherapy by sensitizing cancer cells and protecting normal cells in a variety of cancer models, including glioblastoma (GBM). Cancer cells, unlike normal cells, respond to fasting by promoting oncogenic signaling and protein synthesis. We hypothesized that fasting would increase the replication of oncolytic herpes simplex virus (oHSV) in GBM. Patient-derived GBM cell lines were fasted by growth in glucose and fetal calf serum restricted culture medium. "Transient fasting", 24-hour fasting followed by 24-hour recovery in complete medium, increased late virus gene expression and G47Δ yields about 2-fold in GBM cells, but not in human astrocytes, and enhanced G47Δ killing of GBM cells. Mechanistically, "transient fasting" suppressed phosphorylation of the subunit of eukaryotic initiation factor 2α (eIF2α) and c-Jun N-terminal kinases (JNK) in GBM cells, but not in astrocytes. Pharmacological inhibition of JNK also increased G47Δ yield. In vivo, transient fasting (48-hour food restriction and 24-hour recovery) doubled luciferase activity after intratumoral G47Δ-US11fluc injection into orthotopic GBM xenografts. Thus, "transient fasting" increases G47Δ replication and oncolytic activity in human GBM cells. These results suggest that "transient fasting" may be effectively combined to enhance oncolytic HSV therapy of GBM. PMID:27186404

  13. Protein arginine methyltransferase 1 regulates herpes simplex virus replication through ICP27 RGG-box methylation

    SciTech Connect

    Yu, Jungeun; Shin, Bongjin; Park, Eui-Soon; Yang, Sujeong; Choi, Seunga; Kang, Misun; Rho, Jaerang

    2010-01-01

    Protein arginine methylation is involved in viral infection and replication through the modulation of diverse cellular processes including RNA metabolism, cytokine signaling, and subcellular localization. It has been suggested previously that the protein arginine methylation of the RGG-box of ICP27 is required for herpes simplex virus type-1 (HSV-1) viral replication and gene expression in vivo. However, a cellular mediator for this process has not yet been identified. In our current study, we show that the protein arginine methyltransferase 1 (PRMT1) is a cellular mediator of the arginine methylation of ICP27 RGG-box. We generated arginine substitution mutants in this domain and examined which arginine residues are required for methylation by PRMT1. R138, R148 and R150 were found to be the major sites of this methylation but additional arginine residues serving as minor methylation sites are still required to sustain the fully methylated form of ICP27 RGG. We also demonstrate that the nuclear foci-like structure formation, SRPK interactions, and RNA-binding activity of ICP27 are modulated by the arginine methylation of the ICP27 RGG-box. Furthermore, HSV-1 replication is inhibited by hypomethylation of this domain resulting from the use of general PRMT inhibitors or arginine mutations. Our data thus suggest that the PRMT1 plays a key role as a cellular regulator of HSV-1 replication through ICP27 RGG-box methylation.

  14. Transient fasting enhances replication of oncolytic herpes simplex virus in glioblastoma

    PubMed Central

    Esaki, Shinichi; Rabkin, Samuel D; Martuza, Robert L; Wakimoto, Hiroaki

    2016-01-01

    Short-term nutritional restriction (fasting) has been shown to enhance the efficacy of chemotherapy by sensitizing cancer cells and protecting normal cells in a variety of cancer models, including glioblastoma (GBM). Cancer cells, unlike normal cells, respond to fasting by promoting oncogenic signaling and protein synthesis. We hypothesized that fasting would increase the replication of oncolytic herpes simplex virus (oHSV) in GBM. Patient-derived GBM cell lines were fasted by growth in glucose and fetal calf serum restricted culture medium. “Transient fasting”, 24-hour fasting followed by 24-hour recovery in complete medium, increased late virus gene expression and G47Δ yields about 2-fold in GBM cells, but not in human astrocytes, and enhanced G47Δ killing of GBM cells. Mechanistically, “transient fasting” suppressed phosphorylation of the subunit of eukaryotic initiation factor 2α (eIF2α) and c-Jun N-terminal kinases (JNK) in GBM cells, but not in astrocytes. Pharmacological inhibition of JNK also increased G47Δ yield. In vivo, transient fasting (48-hour food restriction and 24-hour recovery) doubled luciferase activity after intratumoral G47Δ-US11fluc injection into orthotopic GBM xenografts. Thus, “transient fasting” increases G47Δ replication and oncolytic activity in human GBM cells. These results suggest that “transient fasting” may be effectively combined to enhance oncolytic HSV therapy of GBM. PMID:27186404

  15. Interaction of humic acids and humic-acid-like polymers with herpes simplex virus type 1

    NASA Astrophysics Data System (ADS)

    Klöcking, Renate; Helbig, Björn

    The study was performed in order to compare the antiviral activity against herpes simplex virus type 1 (HSV-1) of synthetic humic-acid-like polymers to that of their low-molecular-weight basic compounds and naturally occurring humic acids (HA) in vitro. HA from peat water showed a moderate antiviral activity at a minimum effective concentration (MEC) of 20 µg/ml. HA-like polymers, i.e. the oxidation products of caffeic acid (KOP), hydrocaffeic acid (HYKOP), chlorogenic acid (CHOP), 3,4-dihydroxyphenylacetic acid (3,4-DHPOP), nordihydroguaretic acid (NOROP), gentisinic acid (GENOP), pyrogallol (PYROP) and gallic acid (GALOP), generally inhibit virus multiplication, although with different potency and selectivity. Of the substances tested, GENOP, KOP, 3,4-DHPOP and HYKOP with MEC values in the range of 2 to 10 µg/ml, proved to be the most potent HSV-1 inhibitors. Despite its lower antiviral potency (MEC 40 µg/ml), CHOP has a remarkable selectivity due to the high concentration of this polymer that is tolerated by the host cells (>640 µg/ml). As a rule, the antiviral activity of the synthetic compounds was restricted to the polymers and was not preformed in the low-molecular-weight basic compounds. This finding speaks in favour of the formation of antivirally active structures during the oxidative polymerization of phenolic compounds and, indirectly, of corresponding structural parts in different HA-type substances.

  16. Molecular evaluation of extracellular activity of medicinal herb Clinacanthus nutans against herpes simplex virus type-2.

    PubMed

    Vachirayonstien, Thaveechai; Promkhatkaew, Duanthanorm; Bunjob, Malee; Chueyprom, Asawachai; Chavalittumrong, Pranee; Sawanpanyalert, Pathom

    2010-02-01

    Clinacanthus nutans (Burm. f.) Lindau (C. nutans), a medicinal herb belonging to the family Acanthaceae, has traditionally been used in herpes simplex virus (HSV) treatment in Thailand. Clinical trials have indicated that topical preparations produced from its extracts were effective in HSV-2 treatment. However, there is no clear evidence of the mechanism of action or a molecular target of C. nutans. In this study, the extracellular activity of C. nutans extracts against HSV-2 infected on HEp-2 cells was investigated in terms of its molecular aspects. HSV-2 was treated with the extracts and adsorped into the HEp-2 cells. After infection, HSV-2 DNA quantities in the infected cells were assessed and compared by the quantitative dot blot hybridisation technique. The results showed that treating the viruses with either less or more highly purified extracts before infection resulted in great reductions of viral infectivity. Further investigation was performed by Western blot analysis to determine the activities of the extracts on the viral proteins. At least eight viral proteins of the infected cell proteins (ICP) and some structural proteins, including 146, 125, 78, 69, 55, 44, 40 and 20 KDa proteins, were depleted and reduced gradually with higher and lower concentrated herb extracts, respectively. These suggest that the C. nutans extracts highly inactivated or inhibited HSV-2 before infection. PMID:20140802

  17. Activity of Porphyridium sp. polysaccharide against herpes simplex viruses in vitro and in vivo.

    PubMed

    Huheihel, Mahmoud; Ishanu, Vladimir; Tal, Jacov; Arad, Shoshana Malis

    2002-01-01

    The cell wall sulfated polysaccharide of the red microalga Porphyridium sp. exhibited impressive antiviral activity against herpes simplex virus types 1 and 2 (HSV-1 and -2) both in vitro (cell culture) and in vivo (rats and rabbits). Depending on the concentration, this polysaccharide completely inhibited or slowed down the development of the cytopathic effect in HSV-infected cells, but did not show any cytotoxic effects on vero cells even when a concentration as high as 250 microg/ml was used. There was indirect evidence for a strong interaction between the polysaccharide and HSV and a weak interaction with the cell surface. When tested in vivo, Porphyridium sp. polysaccharide conferred significant and efficient protection against HSV-1 infection: at a concentration as low as 100 microg/ml, it prevented the appearance and development of symptoms of HSV-1 infection in rats and rabbits. The polysaccharide did not exhibit any cytotoxic effects at a concentration of 2 mg/ml in vivo. PMID:11741707

  18. Chromatin structure is required to block transcription of the methylated herpes simplex virus thymidine kinase gene

    SciTech Connect

    Buschhausen, G.; Wittig, B.; Graessmann, M.; Graessmann, A.

    1987-03-01

    Inhibition of herpes simplex virus (HSV) thymidine kinase (TK) gene transcription (pHSV-106, pML-BPV-TK4) by DNA methylation is an indirect effect, which occurs with a latency period of approx. 8 hr microinjection of the DNA into TK/sup -/ rat 2 and mouse LTK/sup -/ cells. The authors have strong evidence that chromatin formation is critical for the transition of the injected DNA from methylation insensitivity to methylation sensitivity. Chromatin was reconstituted in vitro by using methylated and mock-methylated HSV TK DNA and purified chicken histone octamers. After microinjection, the methylated chromatin was always biologically inactive, as tested by autoradiography of the cells after incubation with (/sup 3/H)thymidine and by RNA dot blot analysis. However, in transformed cell lines, reactivation of the methylated chromatic occurred after treatment with 5-azacytidine. Furthermore, integration of the TK chromatin into the host genome is not required to block expression of the methylated TK gene. Mouse cells that contained the pML-BPV-TK4 chromatin permanently in an episomal state also did not support TK gene expression as long as the TK DNA remained methylated.

  19. Mathematical modeling of herpes simplex virus-2 suppression with pritelivir predicts trial outcomes.

    PubMed

    Schiffer, Joshua T; Swan, David A; Magaret, Amalia; Corey, Lawrence; Wald, Anna; Ossig, Joachim; Ruebsamen-Schaeff, Helga; Stoelben, Susanne; Timmler, Burkhard; Zimmermann, Holger; Melhem, Murad R; Van Wart, Scott A; Rubino, Christopher M; Birkmann, Alexander

    2016-02-01

    Pharmacokinetic and pharmacodynamic models estimate the potency of antiviral agents but do not capture viral and immunologic factors that drive the natural dynamics of infection. We designed a mathematical model that synthesizes pharmacokinetics, pharmacodynamics, and viral pathogenesis concepts to simulate the activity of pritelivir, a DNA helicase-primase inhibitor that targets herpes simplex virus. Our simulations recapitulate detailed viral kinetic shedding features in five dosage arms of a phase 2 clinical trial. We identify that in vitro estimates of median effective concentration (EC50) are lower than in vivo values for the drug. Nevertheless, pritelivir potently decreases shedding at appropriate doses based on its mode of action and long half-life. Although pritelivir directly inhibits replication in epithelial cells, our model indicates that pritelivir also indirectly limits downstream viral spread from neurons to genital keratinocytes, within genital ulcers, and from ulcer to new mucosal sites of infection. We validate our model based on its ability to predict outcomes in a subsequent trial with a higher dose. The model can therefore be used to optimize dose selection in clinical practice. PMID:26843190

  20. 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

  1. 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

  2. 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

  3. 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. PMID:25505043

  4. Agents and strategies in development for improved management of herpes simplex virus infection and disease.

    PubMed

    Kleymann, Gerald

    2005-02-01

    The quiet pandemic of herpes simplex virus (HSV) infections has plagued humanity since ancient times, causing mucocutaneous infection such as herpes labialis and herpes genitalis. Disease symptoms often interfere with every-day activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immuno-compromised patient population. After infection the virus persists for life in neurons of the host in a latent form, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently no cure is available. So far, vaccines, ILs, IFNs, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or non-specific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. The recently discovered inhibitors of the HSV helicase-primase are the most potent development candidates today. These antiviral agents act by a novel mechanism of action and display low resistance rates in vitro and superior efficacy in animal models. This review summarises the current therapeutic options, discusses the potential of preclinical or investigational drugs and provides an up-to-date interpretation of the challenge to establish novel treatments for herpes simplex disease. PMID:15757392

  5. 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

  6. CAP37-derived antimicrobial peptides have in vitro antiviral activity against adenovirus and herpes simplex virus type 1

    PubMed Central

    Gordon, Y. Jerold; Romanowski, Eric G.; Shanks, Robert M. Q.; Yates, Kathleen A.; Hinsley, Heather; Pereira, H. Anne

    2009-01-01

    Purpose The antiviral activity of an established antibacterial CAP37 domain and its extracellular mechanism of action were investigated. Methods CAP37-derived peptides modified to assess the importance of disulfide bonds were evaluated in cytotoxicity, and antiviral assays (direct time kill, dose-dependency and TOTO-1) for adenovirus (Ad) and herpes simplex virus type 1 (HSV-1). Results Variable virus, adenovirus serotype-dependant, and dose-dependent inhibition were demonstrated without cytotoxicity. For Peptide A (CAP3720-44), TOTO-1 dye uptake was demonstrated for Ad5 and HSV-1. Conclusions Unlike the antibacterial activity of this CAP37 domain, its antiviral activity is not fully dependent upon disulfide bond formation. Viral inhibition appears to result, in part, from disruption of the envelope and/or capsid. PMID:19274533

  7. Secretory IgA specific for herpes simplex virus in lacrimal fluid from patients with herpes keratitis--a possible diagnostic parameter.

    PubMed Central

    Pedersen, B; Møller Andersen, S; Klauber, A; Ottovay, E; Prause, J U; Zhong, C U; Norrild, B

    1982-01-01

    In the present study a solid-phase radioimmune assay was used for the demonstration of herpes simplex virus-specific IgG and secretory IgA antibodies in the lacrimal fluid from patients with active recurrent herpes keratitis. The method was quantitative and made it possible to test specifically for the production of secretory IgA antibodies produced during an active herpes simplex virus infection. The production of secretory IgA was followed in 2 patients with fresh recurrent lesions. The HSV-specific secretory IgA could be demonstrated during the first 10 days of infection, where the maximal concentration was reached 3-5 days after the first symptoms occurred. The secretory antibodies were locally produced, and it is shown for the first time that herpes virus-specific secretory antibodies were of diagnostic value. PMID:6288066

  8. [Japanese guidelines for the management of herpes simplex encephalitis; comparison with those from the International Management Herpes Forum].

    PubMed

    Shoji, Hiroshi

    2006-11-01

    Herpes simplex encephalitis (HSE) is still recognized as a severe sporadic encephalitis, although the mortality and morbidity rates have been decreased to 10% and 30%, respectively. This disease is diagnosed using clinical symptoms, CSF, EEG, CT, MRI, and virologic tests such as polymerase chain reaction (PCR) or enzyme immunosorbent assay (EIA). Early diagnosis and treatment are essential for HSE. However, the early symptoms of this disease are various, and the laboratory diagnostic criteria are unclear to the non-specialist. In 2005, Japanese guidelines for the management of HSE have been issued via two sets of Workshops at the Japanese Neuroinfectious Disease Congress. The diagnostic and therapeutic criteria were discussed in comparison with those from the International Management Herpes Forum (IMHF) in 2004. For a definitive diagnosis, CSF PCR for herpes simplex virus (HSV) is recommended, and the detection rate has been reported to be 60 to 80% within the 7th day of the illness. In the IMHF, the PCR method has also been the primary method for early diagnosis and for monitoring the therapy. Further, quantitative real-time PCR has become available for measuring the effectiveness of aciclovir therapy. To measure HSV antibody levels, complement antibody (CF), neutralizing antibody (NT), or enzyme-linked immunosorbent assay (ELISA or EIA) are available. Significant elevation of EIA IgG or intrathecal HSV antibody production should be shown, although these antibody responses often appear two weeks after the onset of HSE. Regarding anti-herpesvirus drugs, in both Japanese and IMHF guidelines aciclovir is consistent with the first choice, and it is recommended that its administration would be started as soon as HSE is suspected on the basis of clinical pictures, CT * MRI, EEG, or CSF findings. However, antiviral therapy may be discontinued if a negative CSF HSV PCR is obtained at > 72 hours after onset. A recent Japanese study shows the efficacy of a combination

  9. Adeno-Associated Virus Type 2 Rep68 Can Bind to Consensus Rep-Binding Sites on the Herpes Simplex Virus 1 Genome

    PubMed Central

    Seyffert, Michael; Glauser, Daniel L.; Tobler, Kurt; Georgiev, Oleg; Vogel, Rebecca; Vogt, Bernd; Agúndez, Leticia; Linden, Michael; Büning, Hildegard; Ackermann, Mathias

    2015-01-01

    Adeno-associated virus type 2 is known to inhibit replication of herpes simplex virus 1 (HSV-1). This activity has been linked to the helicase- and DNA-binding domains of the Rep68/Rep78 proteins. Here, we show that Rep68 can bind to consensus Rep-binding sites on the HSV-1 genome and that the Rep helicase activity can inhibit replication of any DNA if binding is facilitated. Therefore, we hypothesize that inhibition of HSV-1 replication involves direct binding of Rep68/Rep78 to the HSV-1 genome. PMID:26292324

  10. Genetic studies of cell fusion induced by herpes simplex virus type 1.

    PubMed Central

    Read, G S; Person, S; Keller, P M

    1980-01-01

    Eight cell fusion-causing syn mutants were isolated from the KOS strain of herpes simplex virus type 1. Unlike the wild-type virus, the mutants produced plaques containing multinucleated cells, or syncytia. Fusion kinetics curves were established with a Coulter Counter assay for the mutants and wild-type virus in single infections of human embryonic lung (HEL) cells, for the mutants and wild-type virus in mixed infections (dominance test), and for pairs of mutants in mixed infections (complementation test). In single infections, fusion began 4 to 6 h after infection and proceeded with an exponential decrease in the number of small single cells. At some later time that was characteristic of the mutant, there was a significant reduction in the rate of fusion for all but possibly one of the mutants. Although the wild-type virus did not produce syncytial plaques, it did induce a small amount of fusion that stopped abruptly about 2 h after it started. These data are consistent with the hypothesis that both mutants and wild type induce an active fusion inducer and that the activity of this inducer is subsequently inhibited. The extent of fusion is apparently determined by the length of the interval during which the fusion inducer is active. That fusion is actively inhibited in wild-type infections is indicated by the observation that syn mutant-infected cells fused more readily with uninfected cells than with wild-type infected cells. Fusion was decreased in mixed infections with the mutants and wild-type virus, but the mutants displayed a codominant fusion phenotype. Fusion was not decreased in mixed infection with pairs of mutants, indicating that the mutants, with one possible exception, are members of the same complementation group. A linkage map was established for six of the mutants by analysis of recombination frequencies. PMID:6251259