Antibody class capture assays for varicella-zoster virus.

PubMed Central

Forghani, B; Myoraku, C K; Dupuis, K W; Schmidt, N J

1984-01-01

Pooled monoclonal antibodies to varicella-zoster virus (VZV) were used as "detector" antibodies in a four-phase enzyme immunofluorescence assay for determination of immunoglobulin M (IgM), IgA, and IgG antibodies to VZV. Polyclonal antisera specific for heavy chains of human IgM, IgA, and IgG were employed as "capture" antibodies on the solid phase. The antibody class capture assay (ACCA) for VZV IgM antibody detected high titers of virus-specific IgM in all patients with varicella and in 5 of 10 zoster patients. VZV IgM antibody was not detected in patients with primary herpes simplex virus infections or in other individuals without active VZV infection, with one exception, a patient with encephalitis who had other serological findings compatible with a reactivated VZV infection. VZV-specific IgA and IgG antibody titers demonstrable by ACCA were compared with those measured by solid-phase indirect enzyme immunofluorescence assay (EIFA). VZV IgA antibody titers detected in patients with varicella and zoster were variable and could not be considered to be reliable markers of active VZV infection. IgA antibody titers detected by ACCA tended to be higher than those demonstrated by solid-phase indirect EIFA in varicella and zoster patients. VZV IgG antibody titers detected by ACCA in patients with varicella, and to a lesser extent in zoster patients, were as high as or higher than those demonstrated by solid-phase indirect EIFA. However, ACCA was totally insensitive in detecting VZV IgG antibody in individuals with past infections with VZV and would not be a suitable approach for determination of immunity status to VZV. PMID:6330163

Salivary Varicella Zoster Virus in Astronauts and in Patients of Herpes Zoster

NASA Technical Reports Server (NTRS)

Mehta, Satish; Pierson, Duane L.

2010-01-01

Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpes viruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpesviruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors? offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

Varicella zoster virus latency

PubMed Central

Eshleman, Emily; Shahzad, Aamir; Cohrs, Randall J

2011-01-01

Primary infection by varicella zoster virus (VZV) typically results in childhood chickenpox, at which time latency is established in the neurons of the cranial nerve, dorsal root and autonomic ganglia along the entire neuraxis. During latency, the histone-associated virus genome assumes a circular episomal configuration from which transcription is epigenetically regulated. The lack of an animal model in which VZV latency and reactivation can be studied, along with the difficulty in obtaining high-titer cell-free virus, has limited much of our understanding of VZV latency to descriptive studies of ganglia removed at autopsy and analogy to HSV-1, the prototype alphaherpesvirus. However, the lack of miRNA, detectable latency-associated transcript and T-cell surveillance during VZV latency highlight basic differences between the two neurotropic herpesviruses. This article focuses on VZV latency: establishment, maintenance and reactivation. Comparisons are made with HSV-1, with specific attention to differences that make these viruses unique human pathogens. PMID:21695042

Herpes zoster in childhood.

PubMed

Leung, Alexander K C; Robson, W Lane M; Leong, Alexander G

2006-01-01

Herpes zoster is caused by reactivation of latent varicella-zoster virus that resides in a dorsal root ganglion. Herpes zoster can develop any time after a primary infection. Because varicella vaccine is a live attenuated virus, herpes zoster can develop in a vaccine recipient. The incidence of herpes zoster among vaccine recipients is about 14 cases per 100,000 person-years. In young children, herpes zoster has a predilection for areas supplied by the cervical and sacral dermatomes. The most common complications are secondary bacterial infection, depigmentation, and scarring. Although the diagnosis of herpes zoster is based on a distinct clinical appearance, viral DNA analysis of the lesion by polymerase chain reaction or restriction fragment length polymorphism is necessary to differentiate wild from vaccine-type viruses. Acyclovir is the treatment of choice for herpes zoster.

Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia

PubMed Central

Steain, Megan; Sutherland, Jeremy P.; Rodriguez, Michael; Cunningham, Anthony L.; Slobedman, Barry

2014-01-01

ABSTRACT Varicella-zoster virus (VZV) is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes latency within the sensory ganglia and can reactivate to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had active herpes zoster. Ganglia innervating the site of the cutaneous herpes zoster rash showed evidence of necrosis, secondary to vasculitis, or localized hemorrhage. Despite this, there was limited evidence of VZV antigen expression, although a large inflammatory infiltrate was observed. Characterization of the infiltrating T cells showed a large number of infiltrating CD4+ T cells and cytolytic CD8+ T cells. Many of the infiltrating T cells were closely associated with neurons within the reactivated ganglia, yet there was little evidence of T cell-induced neuronal apoptosis. Notably, an upregulation in the expression of major histocompatibility complex class I (MHC-I) and MHC-II molecules was observed on satellite glial cells, implying these cells play an active role in directing the immune response during herpes zoster. This is the first detailed characterization of the interaction between T cells and neuronal cells within ganglia obtained from patients suffering herpes zoster at the time of death and provides evidence that CD4+ and cytolytic CD8+ T cell responses play an important role in controlling VZV replication in ganglia during active herpes zoster. IMPORTANCE VZV is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes a life-long dormant infection within the sensory ganglia and can reawaken to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had

Varicella Zoster Virus and Relapsing Remitting Multiple Sclerosis

PubMed Central

Sotelo, Julio; Corona, Teresa

2011-01-01

Multiple sclerosis (MS) is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV) with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS. PMID:22096629

Subclinical Shed of Infectious Varicella zoster Virus in Astronauts

NASA Technical Reports Server (NTRS)

Cohrs, Randall J.; Mehta, Satish K.; Schmid, D. Scott; Gilden, Donald H.; Pierson, Duane L.

2007-01-01

Aerosol borne varicella zoster virus (VZV) enters the nasopharynx and replicates in tonsillar T-cells, resulting in viremia and varicella (chickenpox). Virus then becomes latent in cranial nerve, dorsal root and autonomic nervous system ganglia along the entire neuraxis (1). Decades later, as cell-mediated immunity to VZV declines (4), latent VZV can reactivate to produce zoster (shingles). Infectious VZV is present in patients with varicella or zoster, but shed of infectious virus in the absence of disease has not been shown. We previously detected VZV DNA in saliva of astronauts during and shortly after spaceflight, suggesting stress induced subclinical virus reactivation (3). We show here that VZV DNA as well as infectious virus in present in astronaut saliva. VZV DNA was detected in saliva during and after a 13-day spaceflight in 2 of 3 astronauts (Fig. panel A). Ten days before liftoff, there was a rise in serum anti-VZV antibody in subjects 1 and 2, consistent with virus reactivation. In subject 3, VZV DNA was not detected in saliva, and there was no rise in anti-VZV antibody titer. Subject 3 may have been protected from virus reactivation by having zoster <10 years ago, which provides a boost in cell-medicated immunity to VZV (2). No VZV DNA was detected in astronaut saliva months before spaceflight, or in saliva of 10 age/sex-matched healthy control subjects sampled on alternate days for 3 weeks (88 saliva samples). Saliva taken 2-6 days after landing from all 3 subjects was cultured on human fetal lung cells (Fig. panel B). Infectious VZV was recovered from saliva of subjects 1 and 2 on the second day after landing. Virus specificity was confirmed by antibody staining and DNA analysis which showed it to be VZV of European descent, common in the US (5). Further, both antibody staining and DNA PCR demonstrated that no HSV-1 was detected in any infected culture. This is the first report of infectious VZV shedding in the absence of clinical disease

Varicella-zoster virus vaccine, successes and difficulties.

PubMed

Sarkadi, Julia

2013-12-01

Despite intensive efforts in recent decades to develop preventive or therapeutic vaccines against diseases caused by herpes simplex virus (HSV), or varicella-zoster virus (VZV), members of the Alpha herpes virinae subfamily of human herpes viruses,a safe and efficient vaccine has been approved for commercial development only against VZV. The VZV vaccine contains a live attenuated strain, OKA. It consists of amixture of at least 13 subpopulations of viruses, all with deletions, insertions or mutations in the genome; the most common mutations are observed in the open reading frame 62 (ORF62). Experience over more than 30 years in Japan, the USA and other countries where VZV vaccination is provided has demonstrated that the vaccine is safe and the effectiveness of two doses compared to unvaccinated children is 98-99%. When administered in a higher dose to stimulate the declining cell-mediated immunity, the same vaccine has been shown to reduce the incidence and severity of herpes zoster in immunocompetent individuals older than 60 years. Vaccination of immuno-compromised subjects with this VZV vaccine is problematic and various strategies need to be explored. Differences in the pathomechanisms of infection, latency and immune evasion of VZV and HSV, together with host genetic factors, may explain the availability of the successful VZV vaccine and the failures of the past HSV vaccine candidates.

Incidence of herpes zoster and seroprevalence of varicella-zoster virus in young adults of South Korea.

PubMed

Kang, Cheol-In; Choi, Chang-Min; Park, Tae-Sung; Lee, Dong-Jun; Oh, Myoung-don; Choe, Kang-Won

2008-05-01

This study was performed to determine the incidence of herpes zoster and seroprevalence of varicella-zoster virus (VZV) in young adults of South Korea, where VZV seroprevalence remains relatively high. In South Korea, military service is compulsory for all healthy young men and hence those in military service might provide a reflection of the general population. The computerized database of the Armed Forces Medical Command was examined to identify the number of reported herpes zoster cases. In order to evaluate VZV seroprevalence, serum samples were obtained from randomly selected subjects among those who had been admitted to the Armed Forces Capital Hospital. A total of 705 cases of herpes zoster were reported between June 2004 and May 2005. The annual incidence rate of herpes zoster was 141 (95% CI 131.0-151.8) per 100000 population. A total of 192 subjects were enrolled for the analysis of VZV seroprevalence. All subjects were male and their median age was 21 (range 19-24) years. The overall anti-VZV IgG seropositivity prevalence was 92.7% (178/192, 95% CI 88.0-95.7%). We have described a population-based study of the epidemiology of VZV infections in the military personnel of South Korea.

Efficacy of live zoster vaccine in preventing zoster and postherpetic neuralgia.

PubMed

Gilden, D

2011-05-01

Declining cell-mediated immunity to varicella zoster virus (VZV) in elderly individuals results in virus reactivation manifest by zoster (shingles) and postherpetic neuralgia (PHN). To prevent virus reactivation, a new VZV vaccine (Zostavax; Merck) that boosts cell-mediated immunity to VZV was developed. The 3-year Shingles Prevention Study showed that Zostavax significantly reduced burden of disease because of zoster and PHN. Despite its cost-effectiveness for adults aged 65-75 years, as determined in the United States, Canada and UK, <2% of immunocompetent adults over age 60 years in the United States were immunized in 2007. This was because of a combination of lack of patient awareness of the vaccine, physicians' uncertainty about the duration of protection and different cost-sharing plans for immunization. Nevertheless, zoster vaccine is safe, effective and highly recommended for immunization of immunocompetent individuals over age 60 years with no history of recent zoster. © 2011 The Association for the Publication of the Journal of Internal Medicine.

Efficacy of live zoster vaccine in preventing zoster and postherpetic neuralgia

PubMed Central

Gilden, D.

2011-01-01

Declining cell-mediated immunity to varicella zoster virus (VZV) in elderly individuals results in virus reactivation manifest by zoster (shingles) and postherpetic neuralgia (PHN). To prevent virus reactivation, a new VZV vaccine (Zostavax, Merck) that boosts cell-mediated immunity to VZV was developed. The 3-year Shingles Prevention Study showed that Zostavax significantly reduced burden of disease due to zoster and PHN. Despite its cost-effectiveness for adults ages 65 to 75 years, as determined in the US, Canada and UK, less than 2% of immunocompetent adults over age 60 years in the US were immunized in 2007. This was due to a combination of lack of patient awareness of the vaccine, physicians’ uncertainty about the duration of protection, and different cost-sharing plans for immunization. Nevertheless, zoster vaccine is safe, effective, and highly recommended for immunization of immunocompetent individuals over age 60 years with no history of recent zoster. PMID:21294791

Risk of Herpes Zoster and Disseminated Varicella Zoster in Patients Taking Immunosuppressant Drugs at the Time of Zoster Vaccination.

PubMed

Cheetham, T Craig; Marcy, S Michael; Tseng, Hung-Fu; Sy, Lina S; Liu, In-Lu Amy; Bixler, Felicia; Baxter, Roger; Donahue, James G; Naleway, Allison L; Jacobsen, Steven J

2015-07-01

To determine the risks associated with zoster vaccine when administered to patients taking immunosuppressant medications. Patients enrolled in 1 of 7 managed care organizations affiliated with the Vaccine Safety Datalink between January 1, 2006, and December 31, 2009, were eligible. The exposure of interest was zoster vaccination in patients with current or remote immunosuppressant drug use. The primary outcomes were disseminated varicella zoster virus (VZV) and herpes zoster in the 42 days after vaccination. Automated data were collected on immunosuppressant drugs and baseline medical conditions. A logistic regression model using inverse probability treatment weights was used to estimate the odds of developing VZV or herpes zoster. A total of 14,554 individuals had an immunosuppressant medication dispensed around the time of vaccination, including 4826 with current use and 9728 with remote use. Most patients were taking low-dose corticosteroids. No cases of disseminated VZV were found in the current or remote users. The risk of herpes zoster was elevated in the 42 days after vaccination in current vs remote users (adjusted odds ratio, 2.99; 95% CI, 1.58-5.70). We found that patients taking immunosuppressant medications at the time of vaccination had a modest increased risk of herpes zoster in the 42 days after vaccination. The development of herpes zoster within 42 days after vaccination suggests that this is more likely due to reactivation of latent zoster virus than dissemination of the vaccine-derived varicella virus. These findings support the current zoster vaccination guidelines. Copyright © 2015 Mayo Foundation for Medical Education and Research. All rights reserved.

Epidemic Varicella Zoster Virus among University Students, India.

PubMed

Meyers, Josh; Logaraj, Muthunarayanan; Ramraj, Balaji; Narasimhan, Padmanesan; MacIntyre, C Raina

2018-02-01

We investigated a yearlong varicella zoster virus outbreak in a highly susceptible young adult population at a large university in India. Outbreaks of varicella infection among adults are not well described in the literature. Infection control measures and vaccination policy for this age group and setting are needed.

Varicella-zoster virus complements herpes simplex virus type 1 temperature-sensitive mutants.

PubMed Central

Felser, J M; Straus, S E; Ostrove, J M

1987-01-01

Varicella-zoster virus (VZV) can complement temperature-sensitive mutants of herpes simplex virus. Of seven mutants tested, two, carrying mutations in the immediate-early ICP4 and ICP27 proteins, were complemented. This complementation was not seen in coinfections with adenovirus type 5 or cytomegalovirus. Following transfection into CV-1 cells, a DNA fragment containing the VZV short repeat sequence complemented the ICP4 mutant. These data demonstrate a functional relationship between VZV and herpes simplex virus and have allowed localization of a putative VZV immediate-early gene. PMID:3023701

Epidemic Varicella Zoster Virus among University Students, India

PubMed Central

Logaraj, Muthunarayanan; Ramraj, Balaji; Narasimhan, Padmanesan; MacIntyre, C. Raina

2018-01-01

We investigated a yearlong varicella zoster virus outbreak in a highly susceptible young adult population at a large university in India. Outbreaks of varicella infection among adults are not well described in the literature. Infection control measures and vaccination policy for this age group and setting are needed. PMID:29350152

Aberrant intracellular localization of Varicella-Zoster virus regulatory proteins during latency

PubMed Central

Lungu, Octavian; Panagiotidis, Christos A.; Annunziato, Paula W.; Gershon, Anne A.; Silverstein, Saul J.

1998-01-01

Varicella-Zoster virus (VZV) is a herpesvirus that becomes latent in sensory neurons after primary infection (chickenpox) and subsequently may reactivate to cause zoster. The mechanism by which this virus maintains latency, and the factors involved, are poorly understood. Here we demonstrate, by immunohistochemical analysis of ganglia obtained at autopsy from seropositive patients without clinical symptoms of VZV infection that viral regulatory proteins are present in latently infected neurons. These proteins, which localize to the nucleus of cells during lytic infection, predominantly are detected in the cytoplasm of latently infected neurons. The restriction of regulatory proteins from the nucleus of latently infected neurons might interrupt the cascade of virus gene expression that leads to a productive infection. Our findings raise the possibility that VZV has developed a novel mechanism for maintenance of latency that contrasts with the transcriptional repression that is associated with latency of herpes simplex virus, the prototypic alpha herpesvirus. PMID:9618542

Pathogenesis and Current Approaches to Control of Varicella-Zoster Virus Infections

PubMed Central

Gershon, Michael D.

2013-01-01

SUMMARY Varicella-zoster virus (VZV) was once thought to be a fairly innocuous pathogen. That view is no longer tenable. The morbidity and mortality due to the primary and secondary diseases that VZV causes, varicella and herpes zoster (HZ), are significant. Fortunately, modern advances, including an available vaccine to prevent varicella, a therapeutic vaccine to diminish the incidence and ameliorate sequelae of HZ, effective antiviral drugs, a better understanding of VZV pathogenesis, and advances in diagnostic virology have made it possible to control VZV in the United States. Occult forms of VZV-induced disease have been recognized, including zoster sine herpete and enteric zoster, which have expanded the field. Future progress should include development of more effective vaccines to prevent HZ and a more complete understanding of the consequences of VZV latency in the enteric nervous system. PMID:24092852

Zeroing in on zoster: a tale of many disorders produced by one virus

PubMed Central

Galetta, Kristin M.; Gilden, Don

2015-01-01

While herpes zoster infection has been recognized since antiquity, chickenpox (varicella) was confused with smallpox until the 1800s, when both illnesses became better understood. In the 20th century, varicella zoster virus (VZV) was shown to cause varicella upon primary (first-time) infection and herpes zoster (shingles) after reactivation of latent VZV. Scientific progress over the past 50 years has rapidly advanced the understanding and prevention of disease produced by VZV. Combined imaging and virological studies continue to reveal the protean neurological, ocular and visceral disorders produced by VZV. PMID:26454371

Zoster Vaccination Increases the Breadth of CD4+ T Cells Responsive to Varicella Zoster Virus

PubMed Central

Laing, Kerry J.; Russell, Ronnie M.; Dong, Lichun; Schmid, D. Scott; Stern, Michael; Magaret, Amalia; Haas, Jürgen G.; Johnston, Christine; Wald, Anna; Koelle, David M.

2015-01-01

Background. The live, attenuated varicella vaccine strain (vOka) is the only licensed therapeutic vaccine. Boost of varicella zoster virus (VZV)–specific cellular immunity is a likely mechanism of action. We examined memory CD4+ T-cell responses to each VZV protein at baseline and after zoster vaccination. Methods. Serial blood samples were collected from 12 subjects vaccinated with Zostavax and immunogenicity confirmed by ex vivo VZV-specific T-cell and antibody assays. CD4+ T-cell lines enriched for VZV specificity were generated and probed for proliferative responses to every VZV protein and selected peptide sets. Results. Zoster vaccination increased the median magnitude (2.3-fold) and breadth (4.2-fold) of VZV-specific CD4+ T cells one month post-vaccination. Both measures declined by 6 months. The most prevalent responses at baseline included VZV open reading frames (ORFs) 68, 4, 37, and 63. After vaccination, responses to ORFs 40, 67, 9, 59, 12, 62, and 18 were also prevalent. The immunogenicity of ORF9 and ORF18 were confirmed using peptides, defining a large number of discrete CD4 T-cell epitopes. Conclusions. The breadth and magnitude of the VZV-specific CD4+ T-cell response increase after zoster vaccination. In addition to glycoprotein E (ORF68), we identified antigenic ORFs that may be useful components of subunit vaccines. PMID:25784732

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vafai, A.; Wellish, M.; Devlin, M.

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 proteinsmore » in human sensory ganglia.« less

Towards Personalized Medicine Mediated by in Vitro Virus-Based Interactome Approaches

PubMed Central

Ohashi, Hiroyuki; Miyamoto-Sato, Etsuko

2014-01-01

We have developed a simple in vitro virus (IVV) selection system based on cell-free co-translation, using a highly stable and efficient mRNA display method. The IVV system is applicable to the high-throughput and comprehensive analysis of proteins and protein–ligand interactions. Huge amounts of genomic sequence data have been generated over the last decade. The accumulated genetic alterations and the interactome networks identified within cells represent a universal feature of a disease, and knowledge of these aspects can help to determine the optimal therapy for the disease. The concept of the “integrome” has been developed as a means of integrating large amounts of data. We have developed an interactome analysis method aimed at providing individually-targeted health care. We also consider future prospects for this system. PMID:24756093

Recombination of Globally Circulating Varicella-Zoster Virus

PubMed Central

Depledge, Daniel P.; Kundu, Samit; Atkinson, Claire; Brown, Julianne; Haque, Tanzina; Hussaini, Yusuf; MacMahon, Eithne; Molyneaux, Pamela; Papaevangelou, Vassiliki; Sengupta, Nitu; Koay, Evelyn S. C.; Tang, Julian W.; Underhill, Gillian S.; Grahn, Anna; Studahl, Marie; Breuer, Judith; Bergström, Tomas

2015-01-01

ABSTRACT Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. IMPORTANCE Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the

Herpes zoster

PubMed Central

Schmader, Kenneth

2016-01-01

Synopsis Herpes zoster afflicts millions of older adults annually worldwide and causes significant suffering due to acute and chronic pain, or postherpetic neuralgia (PHN). Herpes zoster is caused by the reactivation of varicella-zoster virus (VZV) in sensory ganglia in the setting of age, disease and drug-related decline in cellular immunity to VZV. VZV-induced neuronal destruction and inflammation causes the principal problems of pain, interference with activities of daily living and reduced quality of life in older adults. To address these problems, the optimal treatment of herpes zoster requires early antiviral therapy and careful pain management. For patients who develop PHN, evidence-based pharmacotherapy using topical lidocaine patch, gabapentin, pregabalin, tricyclic antidepressants, and/or opiates can reduce pain burden. The live attenuated zoster vaccine is effective in reducing pain burden and preventing herpes zoster and PHN in older adults. PMID:17631237

Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination.

PubMed

Jastrzebski, Andre; Brownstein, Seymour; Ziai, Setareh; Saleh, Solin; Lam, Kay; Jackson, W Bruce

2017-06-01

We present a case of reactivated herpes zoster keratouveitis of 6 years duration with corneal perforation requiring penetrating keratoplasty shortly after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada). Retrospective case report. A 67-year-old woman with a 5-year history of recurrent unilateral herpes zoster keratouveitis in her right eye presented with another recurrence 2 weeks after Zostavax vaccination. Three months later, she developed descemetocele and 2 months afterward, corneal perforation, which was managed by penetrating keratoplasty. Immunohistopathological examination disclosed positive staining for varicella zoster virus in most of the keratocytes adjacent to the descemetocele and perforation, most vividly in the deeper two-thirds of the stroma where the keratocytes were most dense, but not in corneal epithelium or endothelium. Electron microscopic examination showed universally severely degenerated corneal keratocytes in the corneal stroma adjacent to the perforation with variable numbers of herpes virus capsids present in half of these cells. Only a rare normal-appearing keratocyte was identified in the more peripheral corneal stroma. We present a case of reactivation of herpes keratouveitis shortly after vaccination with Zostavax in a patient with previous herpes zoster ophthalmicus. We demonstrate, for the first time, ultrastructural evidence consistent with inactive virus capsids in diffusely degenerated keratocytes in the extracted corneal tissue.

Herpes zoster could be an early manifestation of undiagnosed human immunodeficiency virus infection.

PubMed

Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu; Chen, Wen-Chi

2016-05-01

No formal epidemiological research based on systematic analysis has focused on the relationship between herpes zoster and immunodeficiency virus (HIV) infection in Taiwan. Our aim was to explore whether herpes zoster is an early manifestation of undiagnosed human HIV infection in Taiwan. This was a retrospective cohort study using the database of the Taiwan National Health Insurance Program. A total of 35,892 individuals aged ≤ 84 years with newly diagnosed herpes zoster from 1998 to 2010 were assigned to the herpes zoster group, whereas 143,568 sex-matched and age-matched, randomly selected individuals without herpes zoster served as the non-herpes zoster group. The incidence of HIV diagnosis at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence interval (CI) for risk of HIV diagnosis associated with herpes zoster and other comorbidities including drug dependence and venereal diseases. The overall incidence of HIV diagnosis was 4.19-fold greater in the herpes zoster group than that in the non-herpes zoster group (3.33 per 10,000 person-years vs. 0.80 per 10,000 person-years, 95% CI 4.04-4.35). The multivariable Cox proportional hazards regression analysis revealed that the adjusted hazard ratio of HIV diagnosis was 4.37 (95% CI 3.10-6.15) for individuals with herpes zoster and without comorbidities, as compared with individuals without herpes zoster and without comorbidities. Herpes zoster is associated with HIV diagnosis. Patients who have risk behaviors of HIV infection should receive regular surveillance for undiagnosed HIV infection when they present with herpes zoster. Copyright © 2015. Published by Elsevier B.V.

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus*

PubMed Central

Bagdonaite, Ieva; Nordén, Rickard; Joshi, Hiren J.; King, Sarah L.; Vakhrushev, Sergey Y.; Olofsson, Sigvard; Wandall, Hans H.

2016-01-01

Herpesviruses are among the most complex and widespread viruses, infection and propagation of which depend on envelope proteins. These proteins serve as mediators of cell entry as well as modulators of the immune response and are attractive vaccine targets. Although envelope proteins are known to carry glycans, little is known about the distribution, nature, and functions of these modifications. This is particularly true for O-glycans; thus we have recently developed a “bottom up” mass spectrometry-based technique for mapping O-glycosylation sites on herpes simplex virus type 1. We found wide distribution of O-glycans on herpes simplex virus type 1 glycoproteins and demonstrated that elongated O-glycans were essential for the propagation of the virus. Here, we applied our proteome-wide discovery platform for mapping O-glycosites on representative and clinically significant members of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. Because glycosylation is highly dependent on the host cell, we tested varicella zoster virus-infected cell lysates and clinically isolated virus and found evidence of consistent O-glycosites. These results present a comprehensive view of herpesvirus O-glycosylation and point to the widespread occurrence of O-glycans in regions of envelope proteins important for virus entry, formation, and recognition by the host immune system. This knowledge enables dissection of specific functional roles of individual glycosites and, moreover, provides a framework for design of glycoprotein vaccines with representative glycosylation. PMID:27129252

Modelling the impact of a combined varicella and zoster vaccination programme on the epidemiology of varicella zoster virus in England.

PubMed

van Hoek, Albert Jan; Melegaro, Alessia; Zagheni, Emelio; Edmunds, W John; Gay, Nigel

2011-03-16

This study updates previous work on modelling the incidence of varicella and Herpes Zoster (HZ) following the introduction of childhood vaccination. The updated model includes new data on age-specific contact patterns, as well as data on the efficacy of zoster vaccination in the elderly and allows for HZ among vaccinees. The current study also looks at two-dose varicella childhood programmes, and assesses the combined impact of varicella vaccination in childhood and zoster vaccination of the elderly. The results suggest that a two-dose schedule is likely to reduce the incidence of varicella to very low levels, provided first dose coverage is around 90% and second dose coverage is in excess of 70%. Single dose varicella vaccination programmes are expected to result in large numbers of breakthrough cases. Childhood vaccination is expected to increase the incidence of zoster for more than 40 years after introduction of the programme, the magnitude of this increase being influenced primarily by the duration of boosting following exposure to the varicella zoster virus. Though this increase in zoster incidence can be partly offset by vaccination of the elderly, the effectiveness of this combined strategy is limited, as much of the increase occurs in those adults too young to be vaccinated. Childhood vaccination at intermediate levels of coverage (70% and 60% for first and second dose coverage respectively) is expected to lead to an increase in adult varicella. At high coverage (90% and 80% coverage) this is unlikely to be the case. These results will be used to inform a cost-effectiveness analysis of combined varicella and zoster vaccination programmes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prediction of GCRV virus-host protein interactome based on structural motif-domain interactions.

PubMed

Zhang, Aidi; He, Libo; Wang, Yaping

2017-03-02

Grass carp hemorrhagic disease, caused by grass carp reovirus (GCRV), is the most fatal causative agent in grass carp aquaculture. Protein-protein interactions between virus and host are one avenue through which GCRV can trigger infection and induce disease. Experimental approaches for the detection of host-virus interactome have many inherent limitations, and studies on protein-protein interactions between GCRV and its host remain rare. In this study, based on known motif-domain interaction information, we systematically predicted the GCRV virus-host protein interactome by using motif-domain interaction pair searching strategy. These proteins derived from different domain families and were predicted to interact with different motif patterns in GCRV. JAM-A protein was successfully predicted to interact with motifs of GCRV Sigma1-like protein, and shared the similar binding mode compared with orthoreovirus. Differentially expressed genes during GCRV infection process were extracted and mapped to our predicted interactome, the overlapped genes displayed different tissue expression distributions on the whole, the overall expression level in intestinal is higher than that of other three tissues, which may suggest that the functions of these genes are more active in intestinal. Function annotation and pathway enrichment analysis revealed that the host targets were largely involved in signaling pathway and immune pathway, such as interferon-gamma signaling pathway, VEGF signaling pathway, EGF receptor signaling pathway, B cell activation, and T cell activation. Although the predicted PPIs may contain some false positives due to limited data resource and poor research background in non-model species, the computational method still provide reasonable amount of interactions, which can be further validated by high throughput experiments. The findings of this work will contribute to the development of system biology for GCRV infectious diseases, and help guide the

Cutaneous varicella zoster virus infection following zoster vaccination: report of post-vaccination herpes zoster skin infection and literature review of zoster vaccination efficacy and guidelines.

PubMed

Stiff, Katherine M; Cohen, Philip R

2017-06-15

BackgroundHerpes zoster vaccine is currently recommended in the United States for immune competent individuals ≥60 years. The efficacy of the herpes zoster vaccine decreases with age and with time following vaccination.PurposeAn elderly man with herpes zoster following vaccination is described. The guidelines for vaccination and issues regarding re-vaccination are reviewed. PubMed was used to search the following terms: efficacy, elderly, herpes zoster, herpes zoster incidence, herpes zoster recurrence, and vaccination. The papers and relevant citations were reviewed. The clinical features of a patient with post-vaccination herpes zoster skin infection are presented; in addition, vaccine efficacy and guidelines are reviewed.ResultsA 91-year-old man, vaccinated for herpes zoster 10 years earlier, presented with crusted erosions on his face corresponding to the area innervated by the ophthalmic division of the left trigeminal nerve. Evaluation using polymerase chain reaction confirmed the diagnosis of herpes zoster.ConclusionsHerpes zoster vaccine decreases in efficacy with both age and number of years following vaccination. Therefore, booster shots or revaccination in the older population may be of benefit.

Herpes Zoster Vaccination: Controversies and Common Clinical Questions.

PubMed

Van Epps, Puja; Schmader, Kenneth E; Canaday, David H

2016-01-01

Herpes zoster, clinically referred to as shingles, is an acute, cutaneous viral infection caused by reactivation of the varicella zoster virus, the same virus that causes chickenpox. The incidence of herpes zoster and its complications increase with decline in cell-mediated immunity, including age-associated decline. The most effective management strategy for herpes zoster is prevention of the disease through vaccination in those who are most vulnerable. Despite the demonstrated efficacy in reducing the incidence and severity of herpes zoster, the uptake of vaccine remains low. Here, we will discuss the controversies that surround the live herpes zoster vaccine and address the common clinical questions that arise. We will also discuss the new adjuvanted herpes zoster vaccine currently under investigation. © 2015 S. Karger AG, Basel.

Burning mouth syndrome associated with varicella zoster virus.

PubMed

Nagel, Maria A; Gilden, Don

2016-07-05

We present two cases of burning mouth syndrome (BMS)-of 8-month duration in a 61-year-old woman and of 2-year duration in a 63-year-old woman-both associated with increased levels of antivaricella zoster virus (VZV) IgM antibodies in serum and with pain that improved with antiviral treatment. Combined with our previous finding of BMS due to herpes simplex virus type 1 (HSV-1) infection, we recommend evaluation of patients with BMS not only for VZV or HSV-1 DNA in the saliva, but also for serum anti-VZV and anti-HSV-1 IgM antibodies. Both infections are treatable with oral antiviral agents. 2016 BMJ Publishing Group Ltd.

Chronic active VZV infection manifesting as zoster sine herpete, zoster paresis and myelopathy.

PubMed

Morita, Y; Osaki, Y; Doi, Y; Forghani, B; Gilden, D H

2003-08-15

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.

Varicella zoster virus-specific immune responses to a herpes zoster vaccine in elderly recipients with major depression and the impact of antidepressant medications.

PubMed

Irwin, Michael R; Levin, Myron J; Laudenslager, Mark L; Olmstead, Richard; Lucko, Anne; Lang, Nancy; Carrillo, Carmen; Stanley, Harold A; Caulfield, Michael J; Weinberg, Adriana; Chan, Ivan S F; Clair, Jim; Smith, Jeff G; Marchese, R D; Williams, Heather M; Beck, Danielle J; McCook, Patricia T; Zhang, Jane H; Johnson, Gary; Oxman, Michael N

2013-04-01

The Depression Substudy of the Shingles Prevention Study (SPS) was designed to evaluate the association between major depression and immune responses to a high-titer live attenuated varicella zoster virus (VZV) vaccine (zoster vaccine), which boosts cell-mediated immunity (CMI) to VZV and decreases the incidence and severity of herpes zoster (HZ). The Depression Substudy was a 2-year longitudinal cohort study in 92 community-dwelling adults≥60 years of age who were enrolled in the SPS, a large, double-blind, placebo-controlled Veterans Affairs Cooperative zoster vaccine efficacy study. Forty subjects with major depressive disorder, stratified by use of antidepressant medications, and 52 age- and sex-matched controls with no history of depression or other mental illness had their VZV-CMI measured prior to vaccination with zoster vaccine or placebo and at 6 weeks, 1 year, and 2 years postvaccination. Depressed subjects who were not treated with antidepressant medications had lower levels of VZV-CMI following administration of zoster vaccine than nondepressed controls or depressed subjects receiving antidepressants even when antidepressant medications failed to alter depressive symptom severity (P<.005). Similar results were obtained taking into account the time-varying status of depression and use of antidepressant medications, as well as changes in depressive symptoms, during the postvaccination period. Depressed patients have diminished VZV-CMI responses to zoster vaccine, and treatment with antidepressant medication is associated with normalization of these responses. Because higher levels of VZV-CMI correlate with lower risk and severity of HZ, untreated depression may increase the risk and severity of HZ and reduce the efficacy of zoster vaccine.

A rapid radioimmunoassay using /sup 125/I-labeled staphylococcal protein A for antibody to varicella-zoster virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richman, D.D.; Cleveland, P.H.; Oxman, M.N.

1981-05-01

A sensitive radioimmunoassay for serum antibody to varicella-zoster virus is described; it uses 125I-labeled staphylococcal protein A and a specially designed immunofiltration apparatus. The assay accurately distinguishes between individuals who are susceptible and those who are immune to infection with varicella-zoster virus. In addition, it can detect passive antibody in recipients of varicella-zoster immune globulin. This radioimmunoassay also detects the heterologous antibody responses that occasionally occur in patients infected with herpes simplex virus, which also have been detected by other antibody assays. The particular advantages of this assay are the use of noninfectious reagents, the speed of execution (less thanmore » 3 hr), the requirement for only small quantities of serum (30 microliters), the objectivity of end-point determination, and the capability of screening large numbers of sera. Consequently, this radioimmunoassay is especially useful for the rapid identification of susceptible individuals, which is essential for the appropriate management of patients and hospital personnel after exposure to varicella.« less

Serology indicates cytomegalovirus infection is associated with varicella-zoster virus reactivation.

PubMed

Ogunjimi, Benson; Theeten, Heidi; Hens, Niel; Beutels, Philippe

2014-05-01

Varicella-zoster virus (VZV) causes chickenpox after which the virus remains latent in neural ganglia. Subsequent reactivation episodes occur, leading mainly to subclinical detection of VZV, but also to the clinical entity herpes zoster. These reactivations are known to occur most frequently amongst immunocompromised individuals, but the incidence of herpes zoster is also known to increase with age, supposedly as a consequence of immunosenescence. Our analysis aims to explore associations between cytomegalovirus (CMV) infection and VZV reactivation by analyzing VZV-specific antibody titers as a function of age, gender, and CMV serostatus. The analysis was repeated on measles and parvovirus B19 antibody titers. At the time of the observations, measles virus circulation was virtually eliminated, whereas parvovirus B19 circulated at lower levels than VZV. Multiple linear regression analyses, using the log-transformed antibody titers, identified a positive association between ageing and VZV antibody titers suggesting that ageing increasingly stimulates VZV reactivation. CMV infection further amplified the positive association between ageing and the reactivation rate. A negative association between CMV infection and VZV antibody titers was found in young individuals, thereby supporting the hypothesis that CMV infection may have a negative effect on the number of B-cells. However, no associations between CMV infection and measles or parvovirus B19 antibody titers occurred, but ageing tended to be associated with a decrease in the antibody titer against parvovirus B19. The combined results thus suggest that both CMV-dependent and CMV-independent immunosenescence occurs. This is supported by an in-depth analysis of VZV, measles and parvovirus B19 antibody titers. © 2013 Wiley Periodicals, Inc.

Quantitative interactome reveals that porcine reproductive and respiratory syndrome virus nonstructural protein 2 forms a complex with viral nucleocapsid protein and cellular vimentin.

PubMed

Song, Tao; Fang, Liurong; Wang, Dang; Zhang, Ruoxi; Zeng, Songlin; An, Kang; Chen, Huanchun; Xiao, Shaobo

2016-06-16

Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has heavily impacted the global swine industry. The PRRSV nonstructural protein 2 (nsp2) plays crucial roles in viral replication and host immune regulation, most likely by interacting with viral or cellular proteins that have not yet been identified. In this study, a quantitative interactome approach based on immunoprecipitation and stable isotope labeling with amino acids in cell culture (SILAC) was performed to identify nsp2-interacting proteins in PRRSV-infected cells with an nsp2-specific monoclonal antibody. Nine viral proteins and 62 cellular proteins were identified as potential nsp2-interacting partners. Our data demonstrate that the PRRSV nsp1α, nsp1β, and nucleocapsid proteins all interact directly with nsp2. Nsp2-interacting cellular proteins were classified into different functional groups and an interactome network of nsp2 was generated. Interestingly, cellular vimentin, a known receptor for PRRSV, forms a complex with nsp2 by using viral nucleocapsid protein as an intermediate. Taken together, the nsp2 interactome under the condition of virus infection clarifies a role of nsp2 in PRRSV replication and immune evasion. Viral proteins must interact with other virus-encoded proteins and/or host cellular proteins to function, and interactome analysis is an ideal approach for identifying such interacting proteins. In this study, we used the quantitative interactome methodology to identify the viral and cellular proteins that potentially interact with the nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) under virus infection conditions, thus providing a rich source of potential viral and cellular interaction partners for PRRSV nsp2. Based on the interactome data, we further demonstrated that PRRSV nsp2 and nucleocapsid protein together with cellular vimentin, form a complex that may be essential for viral attachment and

Structural Organization and Strain Variation in the Genome of Varicella Zoster Virus

DTIC Science & Technology

1984-10-23

Zoster 6 Growth of VZV in tissue culture 9 Structure and proteins of VZV 15 Structure of HSV DNA 20 Classification of herpesviruses based on DNA...structure 28 Strain variation in herpesvirus DNA 31 VZV DNA 33 Specific aims 36 II. MATERIALS AND METHODS 38 Cells and viruses 38 Isolation of virus...endonuclease fragments by colony hybridization 106 21. Selected methods of restriction endonuclease mapping .... 109 22. Identification of

Varicella Zoster Complications

PubMed Central

Nagel, Maria A.; Gilden, Don

2013-01-01

Opinion statement Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines and virus reactivates to cause zoster (shingles), which can occur anywhere on the body. Skin lesions resolve within 1-2 weeks, while complete cessation of pain usually takes 4-6 weeks. Zoster can be followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, meningoencephalitis, cerebellitis, myelopathy, multiple ocular disorders and vasculopathy that can mimic giant cell arteritis. All of the neurological and ocular disorders listed above may also develop without rash. Diagnosis of VZV-induced neurological disease may require examination of CSF, serum and/ or ocular fluids. In the absence of rash in a patient with neurological disease potentially due to VZV, CSF should be examined for VZV DNA by PCR and for anti-VZV IgG and IGM. Detection of VZV IgG antibody in CSF is superior to detection of VZV DNA in CSF to diagnose vasculopathy, recurrent myelopathy, and brainstem encephalitis. Oral antiviral drugs speed healing of rash and shorten acute pain. Immunocompromised patients require intravenous acyclovir. First-line treatments for post-herpetic neuralgia include tricyclic antidepressants gabapentin, pregabalin, and topical lidocaine patches. VZV vasculopathy, meningoencephalitis, and myelitis are all treated with intravenous acyclovir. PMID:23794213

Immune response and reactogenicity of intradermal administration versus subcutaneous administration of varicella-zoster virus vaccine: an exploratory, randomised, partly blinded trial.

PubMed

Beals, Chan R; Railkar, Radha A; Schaeffer, Andrea K; Levin, Yotam; Kochba, Efrat; Meyer, Brian K; Evans, Robert K; Sheldon, Eric A; Lasseter, Kenneth; Lang, Nancy; Weinberg, Adriana; Canniff, Jennifer; Levin, Myron J

2016-08-01

The licensed live, attenuated varicella-zoster virus vaccine prevents herpes zoster in adults older than 50 years. We aimed to determine whether intradermal administration of zoster vaccine could enhance vaccine immunogenicity compared with conventional needle subcutaneous administration. In this randomised, dose-ranging study, adults aged 50 years or older who had a history of varicella or who had resided in a country with endemic varicella-zoster virus infection for 30 years or more were eligible. Participants received the approved full or a 1/3 dose of zoster vaccine given subcutaneously or one of four intradermal doses (full, 1/3, 1/10, or 1/27 dose) using the MicronJet600 device. The two subcutaneous doses and the four intradermal doses were randomised (1·5:1:1:1:1:1) by computer generated sequence with randomisation stratified by age (50-59 years or 60 years or older). The primary immunogenicity endpoint was the change from baseline in IgG antibody to varicella-zoster virus-specific glycoproteins (gpELISA) measured at 6 weeks. All patients were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, number NCT01385566. Between Sept 2, 2011, and Jan 13, 2012, 224 participants were enrolled from three clinics in the USA and 223 were randomly assigned: 52 to receive the full dose subcutaneous zoster vaccine, 34 to receive the 1/3 dose subcutaneous zoster vaccine, 34 to receive the full dose intradermal zoster vaccine, 35 to receive the 1/3 dose intradermal zoster vaccine, 34 to receive the 1/10 dose intradermal zoster vaccine, and 34 to receive the 1/27 dose intradermal zoster vaccine. Full dose zoster vaccine given subcutaneously resulted in a gpELISA geometric mean fold-rise (GMFR) of 1·74 (90% CI 1·48-2·04) at 6 weeks post-vaccination compared with intradermal administration which resulted in a significantly higher gpELISA GMFR of 3·25 (2·68-3·94; p<0·0001), which also remained high at 18 months. An apparent dose

Disseminated Herpes Zoster Ophthalmicus in an Immunocompetent 8-Year Old Boy

PubMed Central

Oladokun, Regina Eziuka; Olomukoro, Chikodili N; Owa, Adewale B.

2013-01-01

Varicella results from a primary infection with the varicella virus while herpes zoster is caused by a reactivation of a latent infection. Dissemination of herpes zoster is uncommon in immunocompetent individuals. Reports of disseminated herpes zoster in children are even less common than in adults. An unusual case of disseminated herpes zoster ophthalmicus in an 8-year old immunocompetent black boy is presented. He had a previous primary Varicella zoster virus infection at three years of age. In the current report, he presented during an on-going chicken pox outbreak and survived with no significant complications. A breakthrough varicella virus re-infection or a reactivation is possible, both of which could present as zoster. This case emphasizes the need for prevention of varicella virus infection through universal childhood immunization and effective infection control strategies in health care settings. PMID:24765504

Disseminated herpes zoster ophthalmicus in an immunocompetent 8-year old boy.

PubMed

Oladokun, Regina Eziuka; Olomukoro, Chikodili N; Owa, Adewale B

2013-08-02

Varicella results from a primary infection with the varicella virus while herpes zoster is caused by a reactivation of a latent infection. Dissemination of herpes zoster is uncommon in immunocompetent individuals. Reports of disseminated herpes zoster in children are even less common than in adults. An unusual case of disseminated herpes zoster ophthalmicus in an 8-year old immunocompetent black boy is presented. He had a previous primary Varicella zoster virus infection at three years of age. In the current report, he presented during an on-going chicken pox outbreak and survived with no significant complications. A breakthrough varicella virus re-infection or a reactivation is possible, both of which could present as zoster. This case emphasizes the need for prevention of varicella virus infection through universal childhood immunization and effective infection control strategies in health care settings.

Clinical, epidemiological and etiological studies of adult aseptic meningitis: Report of 11 cases with varicella zoster virus meningitis.

PubMed

Takeshima, Shinichi; Shiga, Yuji; Himeno, Takahiro; Tachiyama, Keisuke; Kamimura, Teppei; Kono, Ryuhei; Takemaru, Makoto; Takeshita, Jun; Shimoe, Yutaka; Kuriyama, Masaru

2017-09-30

We treated 11 cases (52.7 ± 14.9 years, all male) with varicella zoster virus (VZV) meningitis and 437 cases with adult aseptic meningitis from 2004 to 2016. The incidence rate of adult VZV meningitis in the cases with aseptic meningitis was 2.5%. Herpes zoster infections are reported to have occurred frequently in summer and autumn. VZV meningitis also occurred frequently in the similar seasons, in our patients. The diagnoses were confirmed in 9 cases with positive VZV-DNA in the cerebrospinal fluid and in 2 cases with high VZV-IgG indexes (> 2.0). For diagnosis confirmation, the former test was useful for cases within a week of disease onset, and the latter index was useful for cases after a week of disease onset. Zoster preceded the meningitis in 8 cases, while the meningitis preceded zoster in 1 case, and 2 cases did not have zoster (zoster sine herpete). Two patients were carriers of the hepatitis B virus, 1 patient was administered an influenza vaccine 4 days before the onset of meningitis, and 1 patient was orally administered prednisolone for 2 years, for treatment. Their immunological activities might have been suppressed. The neurological complications included trigeminal neuralgia, facial palsy (Ramsay Hunt syndrome), glossopharyngeal neuralgia, and Elsberg syndrome. Because the diseases in some patients can become severe, they require careful treatment.

Microbiology laboratory and the management of mother-child varicella-zoster virus infection

PubMed Central

De Paschale, Massimo; Clerici, Pierangelo

2016-01-01

Varicella-zoster virus, which is responsible for varicella (chickenpox) and herpes zoster (shingles), is ubiquitous and causes an acute infection among children, especially those aged less than six years. As 90% of adults have had varicella in childhood, it is unusual to encounter an infected pregnant woman but, if the disease does appear, it can lead to complications for both the mother and fetus or newborn. The major maternal complications include pneumonia, which can lead to death if not treated. If the virus passes to the fetus, congenital varicella syndrome, neonatal varicella (particularly serious if maternal rash appears in the days immediately before or after childbirth) or herpes zoster in the early years of life may occur depending on the time of infection. A Microbiology laboratory can help in the diagnosis and management of mother-child infection at four main times: (1) when a pregnant woman has been exposed to varicella or herpes zoster, a prompt search for specific antibodies can determine whether she is susceptible to, or protected against infection; (2) when a pregnant woman develops clinical symptoms consistent with varicella, the diagnosis is usually clinical, but a laboratory can be crucial if the symptoms are doubtful or otherwise unclear (atypical patterns in immunocompromised subjects, patients with post-vaccination varicella, or subjects who have received immunoglobulins), or if there is a need for a differential diagnosis between varicella and other types of dermatoses with vesicle formation; (3) when a prenatal diagnosis of uterine infection is required in order to detect cases of congenital varicella syndrome after the onset of varicella in the mother; and (4) when the baby is born and it is necessary to confirm a diagnosis of varicella (and its complications), make a differential diagnosis between varicella and other diseases with similar symptoms, or confirm a causal relationship between maternal varicella and malformations in a newborn

[Four cases of urinary dysfunction associated with sacral herpes zoster].

PubMed

Matsuo, Tomohiro; Oba, Kojiro; Miyata, Yasuyoshi; Igawa, Tsukasa; Sakai, Hideki

2014-02-01

Herpes zoster is caused by the infection of Varicella-Zoster virus. The anatomical distribution of herpes zoster in the sacral area is only 6. 9%1). Moreover, the onset rate of herpes zoster with urinary dysfunction is 0.6%1). The lesion sites of herpes zoster which cause urinary dysfunction are almost lumber and sacral areas. We describe four cases of sacral herpes zoster with urinary dysfunction in this report. All patients were elderly people (66-84 years old), and all patients were administered anti-virus drugs and alpha 1-adrenergic receptor blockers. Because of urinary retention, three patients have performed clean intermittent self-catheterization (CIC) for several weeks. As the lesions of herpes zoster healed, each patient recovered from urinary dysfunction.

Further characterisation of a rat model of varicella zoster virus (VZV)-associated pain

PubMed Central

Hasnie, F. S.; Breuer, J.; Parker, S.; Wallace, V.; Blackbeard, J.; Lever, I.; Kinchington, P.R.; Dickenson, A. H.; Pheby, T.; Rice, A. S. C.

2007-01-01

Persistent herpes zoster-associated pain is a significant clinical problem and an area of largely unmet therapeutic need. Progress in elucidating the underlying pathophysiology of zoster-associated pain and related co-morbidity behaviour, in addition to appropriately targeted drug development has been hindered by the lack of an appropriate animal model. This study further characterises a recently developed rat model of zoster-associated hypersensitivity and investigates (a) response to different viral strains; (b) relationship between viral inoculum concentration (‘dose’) and mechanical hypersensitivity (‘response’); (c) attenuation of virus-associated mechanical hypersensitivity by clinically useful analgesic drugs; and (d) measurement of pain co-morbidity (anxiety-like behaviour) and pharmacological intervention in the open field paradigm (in parallel with models of traumatic peripheral nerve injury). VZV was propagated on fibroblast cells before subcutaneous injection into the glabrous footpad of the left hind limb of adult male Wistar rats. Control animals received injection of uninfected fibroblast cells. Hind-limb reflex withdrawal thresholds to mechanical, noxious thermal and cooling stimuli were recorded at specified intervals post-infection. Infection with all viral strains was associated with a dose-dependent mechanical hypersensitivity but not a thermal or cool hypersensitivity. Systemic treatment with intraperitoneal (i.p.) morphine (2.5mg/kg), amitriptyline (10mg/kg), gabapentin (30mg/kg), (S)-(+)-ibuprofen (20mg/kg) and the cannnabinoid WIN55,212-2 (2mg/kg) but not the antiviral, acyclovir (50mg/kg), was associated with a reversal of mechanical paw withdrawal thresholds. In the open field paradigm, virus-infected and nerve-injured animals demonstrated an anxiety-like pattern of ambulation (reduced entry into the central area of the open arena) which was positively correlated with mechanical hypersensitivity. This may reflect pain

Investigation of varicella-zoster virus infection of lymphocytes by in situ hybridization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koropchak, C.M.; Solem, S.M.; Diaz, P.S.

1989-05-01

Peripheral blood mononuclear cells harboring viral gene sequences were detected during primary varicella-zoster virus (VZV) infection of the human host and the strain 2 guinea pig by in situ hybridization with a /sup 3/H-labeled VZV DNA probe. Activated T lymphocytes were permissive for VZV infection at low frequency in vitro.

Varicella Zoster Virus in Saliva of Patients With Herpes Zoster

NASA Technical Reports Server (NTRS)

Mehta, Satish K.; Tyring, Stephen K.; Gilden, Donald H.; Cohrs, Randall J.; Leal, Melanie J.; Castro, Victoria A.; Feiveson, Alan H.; Ott, C. Mark; Pierson, Duane L.

2007-01-01

Background. VZV DNA is present in saliva of healthy astronauts and patients with Ramsay Hunt syndrome (geniculate zoster). We hypothesized that a prospective analysis of patients with zoster would detect VZV in saliva independent of zoster location. Methods. We treated 54 patients with valacyclovir. On the first treatment day, 7- and 14-days later, pain was scored and saliva examined for VZV DNA. Saliva from six subjects with chronic pain and 14 healthy subjects was similarly studied. Results. Follow-up data was available for 50/54 patients. Pain decreased in 43/50 (86 percent), disappeared in 37 (74 percent), recurred after disappearing in three (6 percent) and increased in four (8 percent). VZV DNA was found in every patient the day treatment was started, decreased in 47/50 (94 percent), transiently increased in three (6 percent) before decreasing, increased in two (4 percent) and disappeared in 41 (82 percent). There was a positive correlation between the presence of VZV DNA and pain, as well as between the VZV DNA copy number and pain (P<0.0005). Saliva of two patients was cultured, and infectious VZV was isolated from one. VZV DNA was present in one patient before rash and in four patients after pain resolved, and not in any control subjects. Conclusion. VZV DNA is present in saliva of zoster patients.

Herpes Zoster Ophthalmicus.

PubMed

Johnson, Julie L; Amzat, Rianot; Martin, Nicolle

2015-09-01

Herpes zoster is a commonly encountered disorder. It is estimated that there are approximately 1 million new cases of herpes zoster in the United States annually, with an incidence of 3.2 per 1000 person-years. Patients with HIV have the greatest risk of developing herpes zoster ophthalmicus compared with the general population. Other risk factors include advancing age, use of immunosuppressive medications, and primary infection in infancy or in utero. Vaccination against the virus is a primary prevention modality. Primary treatments include antivirals, analgesics, and anticonvulsants. Management may require surgical intervention and comanagement with pain specialists, psychiatrists, and infectious disease specialists. Copyright © 2015 Elsevier Inc. All rights reserved.

A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.

PubMed

Mechelli, Rosella; Umeton, Renato; Policano, Claudia; Annibali, Viviana; Coarelli, Giulia; Ricigliano, Vito A G; Vittori, Danila; Fornasiero, Arianna; Buscarinu, Maria Chiara; Romano, Silvia; Salvetti, Marco; Ristori, Giovanni

2013-01-01

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms.

Incidence and Prevention of Herpes Zoster Reactivation in Patients with Autoimmune Diseases.

PubMed

Chakravarty, Eliza F

2017-02-01

Herpes zoster is the reactivation of latent varicella zoster virus usually occurring decades after initial exposure, and manifesting as a painful vesicular rash occurring along one or more dermatomes. Zoster incidence increases with age as cell mediated immunity against latent virus wanes. Epidemiological evidence suggests that individuals with underlying rheumatic diseases are at increased risk for zoster. It remains unclear whether this is due to immunosuppressive medications or from immune dysregulation of the underlying disease. A vaccine against zoster is available for individuals 50 years and older. Theoretical risks remain about using this live-attenuated virus vaccine in immunosuppressed individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

Childhood varicella-zoster virus vaccination in Belgium

PubMed Central

Bilcke, Joke; Jan van Hoek, Albert; Beutels, Philippe

2013-01-01

Aim: To assess the effectiveness and cost-effectiveness of a universal childhood varicella-zoster vaccination programme in Belgium (1) using the most recent Belgian data on varicella-zoster burden, (2) exploring different options for the timing of the second dose, (3) obtaining results with and without exogenous natural boosting, and (4) investigating the possible additional benefit of zoster booster vaccination for adults at age 50 or 60 years. Methods: An extensively studied and improved dynamic model is used to estimate primary and breakthrough chickenpox and zoster cases over time. For a range of vaccination options, we compared the direct costs (health care payer perspective) and health outcomes (including Quality-Adjusted Life-Years (QALYs) lost) associated with chickenpox and herpes zoster.  Estimates of social contact patterns, health care use, costs and QALY losses are almost exclusively based on Belgian databases and surveys. Results and Conclusions: If exogenous natural boosting exists, a net loss in QALYs is expected for several decades after implementing a universal chickenpox vaccination programme, due to an increase in zoster mainly in persons aged 50-80 years. This result holds also for scenarios that minimise or counteract the expected increase in zoster incidence (e.g. additional booster vaccinations in adults). However, if the boosting hypothesis is not true or if costs and QALYs are cumulated over at least 33 to more than 100 years after vaccination (depending on the assumptions made), different options for universal 2-dose vaccination against chickenpox in Belgium would be cost-effective at a vaccine price of €43/dose or lower. PMID:23321955

Rapid Detection of the Varicella Zoster Virus in Saliva

NASA Technical Reports Server (NTRS)

Pierson, Duane L.; Mehta, Satish K.; Cohrs, Randall J.; Gilden, Don H.; Harding, Robert E.

2011-01-01

Varicella zoster virus (VZV) causes chicken pox on first exposure (usually in children), and reactivates from latency causing shingles (usually in adults). Shingles can be extremely painful, causing nerve damage, organ damage, and blindness in some cases. The virus can be life-threatening in immune-compromised individuals. The virus is very difficult to culture for diagnosis, requiring a week or longer. This invention is a rapid test for VZV from a saliva sample and can be performed in a doctor s office. The kit is small, compact, and lightweight. Detec tion is sensitive, specific, and noninvasive (no needles); only a saliva sample is required. The test provides results in minutes. The entire test is performed in a closed system, with no exposure to infectious materials. The components are made mostly of inexpensive plastic injection molded parts, many of which can be purchased off the shelf and merely assembled. All biological waste is contained for fast, efficient disposal. This innovation was made possible because of discovery of a NASA scientists flight experiment showing the presence of VZV in saliva during high stress periods and disease. This finding enables clinicians to quickly screen patients for VZV and treat the ones that show positive results with antiviral medicines. This promotes a rapid recovery, easing of pain and symptoms, and reduces chances of complications from zoster. Screening of high-risk patients could be incorporated as part of a regular physical exam. These patients include the elderly, pregnant women, and immune-compromised individuals. In these patients, VZV can be a life-threatening disease. In both high- and low-risk patients, early detection and treatment with antiviral drugs can dramatically decrease or even eliminate the clinical manifestation of disease.

Stress-induced subclinical reactivation of varicella zoster virus in astronauts

NASA Technical Reports Server (NTRS)

Mehta, Satish K.; Cohrs, Randall J.; Forghani, Bagher; Zerbe, Gary; Gilden, Donald H.; Pierson, Duane L.

2004-01-01

Varicella zoster virus (VZV) becomes latent in human ganglia after primary infection. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell-mediated immunity to the virus. VZV can also reactivate after surgical stress. The unexpected occurrence of thoracic zoster 2 days before space flight in a 47-year-old healthy astronaut from a pool of 81 physically fit astronauts prompted our search for VZV reactivation during times of stress to determine whether VZV can also reactivate after non-surgical stress. We examined total DNA extracted from 312 saliva samples of eight astronauts before, during, and after space flight for VZV DNA by polymerase chain reaction: 112 samples were obtained 234-265 days before flight, 84 samples on days 2 through 13 of space flight, and 116 samples on days 1 through 15 after flight. Before space flight, only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples were positive in all eight astronauts. No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These results indicate that VZV can reactivate subclinically in healthy individuals after non-surgical stress. Copyright 2004 Wiley-Liss, Inc.

Vibrio vulnificus necrotizing fasciitis preceding herpes zoster

PubMed Central

Ha, Kelli Y.; Tyring, Stephen K.

2013-01-01

A 74-year-old white man presented with unilateral radicular pain extending across the left side of his chest and back. A diagnosis of postherpetic neuralgia, a sequela of herpes zoster, was made. Herpes zoster represents a reactivation of the varicella zoster virus that lies dormant in patients with past chickenpox. Risk factors for the disease include advanced age, stress, immunodeficiency, and immunosuppression. Treatment of herpes zoster entails traditional antiviral medications, while prevention may be achieved with a new prophylactic vaccine. PMID:23382617

Varicella-Zoster Virus-Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults.

PubMed

Weinberg, Adriana; Canniff, Jennifer; Rouphael, Nadine; Mehta, Aneesh; Mulligan, Mark; Whitaker, Jennifer A; Levin, Myron J

2017-07-15

The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4 + and CD8 + T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8 + CD57 + senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4 + CD69 + CD57 + PD1 + and CD8 + CD69 + CD57 + PD1 + T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8 + effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4 + and CD8 + proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ. Copyright © 2017 by The American Association of Immunologists, Inc.

Varicella zoster meningitis complicating combined anti-tumor necrosis factor and corticosteroid therapy in Crohn's disease.

PubMed

Ma, Christopher; Walters, Brennan; Fedorak, Richard N

2013-06-07

Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy.

Zoster vaccine (Zostavax): a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults.

PubMed

Sanford, Mark; Keating, Gillian M

2010-02-01

Individuals who have been infected with varicella zoster virus (VZV) are at risk for developing herpes zoster and this risk appears to be related to a decline in VZV-specific cell-mediated immunity (CMI). Zostavax (zoster vaccine) is a one-dose, high-potency, live, attenuated VZV vaccine that boosts VZV-specific CMI and this is its presumed mechanism of action. Zoster vaccine is registered in the EU for use in adults aged >or=50 years for the prevention of herpes zoster and herpes zoster-related postherpetic neuralgia. In the Shingles Prevention Study, a placebo-controlled trial in adults aged >or=60 years (n = 38 546), zoster vaccine led to a sustained boost of VZV-specific CMI. Over a mean herpes zoster surveillance period of 3.1 years, zoster vaccine reduced the herpes zoster-related burden of illness by 61%, reduced the incidence of herpes zoster by 51% and reduced the incidence of postherpetic neuralgia by 67%. Zoster vaccine recipients who developed herpes zoster had a shorter illness duration and severity than placebo recipients who developed herpes zoster. Zoster vaccine had continuing efficacy in a Shingles Prevention Study subpopulation followed for 7 years post-vaccination. Zoster vaccine was generally well tolerated in older adults. While cost-effectiveness estimates in pharmacoeconomic analyses varied widely according to vaccine and herpes zoster parameter cost/benefit estimates, an analysis from a UK perspective found a zoster vaccine immunization programme in adults aged 65 years to be cost effective. In older adults, the zoster vaccine has the potential to significantly reduce the herpes zoster burden of illness by decreasing the incidence of herpes zoster or reducing its severity.

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

PubMed

Kennedy, Peter G E; Rovnak, Joel; Badani, Hussain; Cohrs, Randall J

2015-07-01

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

Ultra-violet radiation is responsible for the differences in global epidemiology of chickenpox and the evolution of varicella-zoster virus as man migrated out of Africa.

PubMed

Rice, Philip S

2011-04-23

Of the eight human herpes viruses, varicella-zoster virus, which causes chickenpox and zoster, has a unique epidemiology. Primary infection is much less common in children in the tropics compared with temperate areas. This results in increased adult susceptibility causing outbreaks, for example in health-care workers migrating from tropical to temperate countries. The recent demonstration that there are different genotypes of varicella-zoster virus and their geographic segregation into tropical and temperate areas suggests a distinct, yet previously unconsidered climatic factor may be responsible for both the clinical and molecular epidemiological features of this virus infection. Unlike other human herpes viruses, varicella-zoster virus does not require intimate contact for infection to occur indicating that transmission may be interrupted by a geographically restricted climatic factor. The factor with the largest difference between tropical and temperate zones is ultra-violet radiation. This could reduce the infectiousness of chickenpox cases by inactivating virus in vesicles, before or after rupture. This would explain decreased transmissibility in the tropics and why the peak chickenpox incidence in temperate zones occurs during winter and spring, when ultra-violet radiation is at its lowest. The evolution of geographically restricted genotypes is also explained by ultra-violet radiation driving natural selection of different virus genotypes with varying degrees of resistance to inactivation, tropical genotypes being the most resistant. Consequently, temperate viruses should be more sensitive to its effects. This is supported by the observation that temperate genotypes are found in the tropics only in specific circumstances, namely where ultra-violet radiation has either been excluded or significantly reduced in intensity. The hypothesis is testable by exposing different virus genotypes to ultra-violet radiation and quantifying virus survival by plaque forming

Ultra-violet radiation is responsible for the differences in global epidemiology of chickenpox and the evolution of varicella-zoster virus as man migrated out of Africa

PubMed Central

2011-01-01

Background Of the eight human herpes viruses, varicella-zoster virus, which causes chickenpox and zoster, has a unique epidemiology. Primary infection is much less common in children in the tropics compared with temperate areas. This results in increased adult susceptibility causing outbreaks, for example in health-care workers migrating from tropical to temperate countries. The recent demonstration that there are different genotypes of varicella-zoster virus and their geographic segregation into tropical and temperate areas suggests a distinct, yet previously unconsidered climatic factor may be responsible for both the clinical and molecular epidemiological features of this virus infection. Presentation of the hypothesis Unlike other human herpes viruses, varicella-zoster virus does not require intimate contact for infection to occur indicating that transmission may be interrupted by a geographically restricted climatic factor. The factor with the largest difference between tropical and temperate zones is ultra-violet radiation. This could reduce the infectiousness of chickenpox cases by inactivating virus in vesicles, before or after rupture. This would explain decreased transmissibility in the tropics and why the peak chickenpox incidence in temperate zones occurs during winter and spring, when ultra-violet radiation is at its lowest. The evolution of geographically restricted genotypes is also explained by ultra-violet radiation driving natural selection of different virus genotypes with varying degrees of resistance to inactivation, tropical genotypes being the most resistant. Consequently, temperate viruses should be more sensitive to its effects. This is supported by the observation that temperate genotypes are found in the tropics only in specific circumstances, namely where ultra-violet radiation has either been excluded or significantly reduced in intensity. Testing the Hypothesis The hypothesis is testable by exposing different virus genotypes to ultra

Latency of Varicella Zoster Virus in Dorsal Root, Cranial, and Enteric Ganglia in Vaccinated Children

PubMed Central

Gershon, Anne A.; Chen, Jason; Davis, Larry; Krinsky, Clarissa; Cowles, Robert; Reichard, Ross; Gershon, Michael

2012-01-01

Despite vaccination, varicella-zoster virus (VZV) remains an important pathogen. We investigated VZV latency in autopsy specimens from vaccinees, in gastrointestinal tissue removed surgically, and in a guinea pig model. We propose that retrograde transport from infected skin and viremia deliver VZV to neurons in which it becomes latent. Wild type (WT) VZV was found to be latent in many ganglia of vaccinated children with no history of varicella, suggesting that subclinical infection with WT-VZV occurs with subsequent viremic dissemination. The 30% to 40% rate of WT-VZV zoster reported in vaccinees and occasional trigeminal zoster due to vaccine type VZV (vOka) are consistent with viremic delivery of VZV to multiple ganglia. Most human intestinal specimens contained latent VZV within neurons of the enteric nervous system (ENS). Induction of viremia in guinea pigs led to VZV latency throughout the ENS. The possibility VZV reactivation in the ENS is an unsuspected cause of gastrointestinal disease requires future investigation. PMID:23303966

Phosphorylation and nuclear localization of the varicella-zoster virus gene 63 protein.

PubMed Central

Stevenson, D; Xue, M; Hay, J; Ruyechan, W T

1996-01-01

The protein encoded by varicella-zoster virus open reading frame 63 and carboxy-terminal deletions of the same were expressed either as fusion proteins at the carboxy terminus of the maltose-binding protein in Escherichia coli or independently in transfected mammalian cells. The truncations contained amino acids 1 to 142 (63 delta N) or 1 to 210 (63 delta K) of the complete 278-amino-acid primary sequence. Recombinant casein kinase II phosphorylated the 63F and 63 delta KF fusion proteins in vitro but did not phosphorylate the 63 delta NF fusion protein, implying that phosphorylation occurred between amino acids 142 and 210. Immunoprecipitation of 35S- or 32P-labelled extracts of cells transfected with plasmids expressing 63, 63 delta N, or 63 delta K also indicated that in situ phosphorylation most likely occurred between amino acids 142 and 210. These combined results suggest that casein kinase II plays a significant role in the phosphorylation of the varicella-zoster virus 63 protein. Indirect immunofluorescence of transfected cells indicated nuclear localization of the 63 protein and cytoplasmic localization of 63 delta K and 63 delta N, implying a requirement for sequences between amino acids 210 and 278 for efficient nuclear localization. PMID:8523589

Herpes zoster - typical and atypical presentations.

PubMed

Dayan, Roy Rafael; Peleg, Roni

2017-08-01

Varicella- zoster virus infection is an intriguing medical entity that involves many medical specialties including infectious diseases, immunology, dermatology, and neurology. It can affect patients from early childhood to old age. Its treatment requires expertise in pain management and psychological support. While varicella is caused by acute viremia, herpes zoster occurs after the dormant viral infection, involving the cranial nerve or sensory root ganglia, is re-activated and spreads orthodromically from the ganglion, via the sensory nerve root, to the innervated target tissue (skin, cornea, auditory canal, etc.). Typically, a single dermatome is involved, although two or three adjacent dermatomes may be affected. The lesions usually do not cross the midline. Herpes zoster can also present with unique or atypical clinical manifestations, such as glioma, zoster sine herpete and bilateral herpes zoster, which can be a challenging diagnosis even for experienced physicians. We discuss the epidemiology, pathophysiology, diagnosis and management of Herpes Zoster, typical and atypical presentations.

[Pain in herpes zoster: Prevention and treatment].

PubMed

Calvo-Mosquera, G; González-Cal, A; Calvo-Rodríguez, D; Primucci, C Y; Plamenov-Dipchikov, P

Shingles is a painful rash that results from reactivation of latent varicella-zoster virus in the dorsal root ganglia or cranial nerves. In this article an update is presented on the prevention and pharmacological treatment of the secondary pain from the virus infection. The most effective way to prevent post-herpetic neuralgia and its consequences is the prevention of herpes itself. A live attenuated vaccine (the Oka strain varicella zoster virus) has been available for several years, and is approved in adults aged 50 years old. Although this vaccine has shown to be effective against herpes zoster and post-herpetic neuralgia, its effectiveness decreases with age and is contraindicated in patients with some form of immunosuppression. Today the recombinant vaccines provide an alternative, and may be administered to immunocompromised persons. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Herpes zoster in children.

PubMed

Peterson, Nathan; Goodman, Seth; Peterson, Michael; Peterson, Warren

2016-08-01

Herpes zoster (HZ) in immunocompetent children is quite uncommon. Initial exposure to the varicella-zoster virus (VZV) may be from a wild-type or vaccine-related strain. Either strain may cause a latent infection and subsequent eruption of HZ. We present a case of HZ in a 15-month-old boy after receiving the varicella vaccination at 12 months of age. A review of the literature regarding the incidence, clinical characteristics, and diagnosis of HZ in children also is provided.

Varicella-Zoster Virus–Specific Immune Responses to Herpes Zoster in Elderly Participants in a Trial of a Clinically Effective Zoster Vaccine

PubMed Central

Zhang, Jane H.; Oxman, Michael N.; Johnson, Gary R.; Hayward, Anthony R.; Caulfield, Michael J.; Irwin, Michael R.; Clair, James; Smith, Jeffrey G.; Stanley, Harold; Marchese, Rocio D.; Harbecke, Ruth; Williams, Heather M.; Chan, Ivan S. F.; Arbeit, Robert D.; Gershon, Anne A.; Schödel, Florian; Morrison, Vicki A.; Kauffman, Carol A.; Straus, Steve E.; Schmader, Kenneth E.; Davis, Larry E.; Levin, Myron J.

2009-01-01

BackgroundThe objectives of this study were to evaluate the association between varicella-zoster virus (VZV)–specific humoral and cell-mediated immunity (CMI) to herpes zoster (HZ) and protection against HZ morbidity and to compare immune responses to HZ and zoster vaccine MethodsIn 981 elderly persons who developed HZ during a zoster vaccine efficacy trial (321 vaccinees and 660 placebo recipients) and 1362 without HZ (682 vaccinees and 680 placebo recipients), CMI was measured by VZV responder cell frequency and interferon-γ enzyme-linked immunospot, and antibodies were measured by VZV enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA) ResultsRobust VZV CMI at HZ onset correlated with reduced HZ morbidity, whereas VZV gpELISA titers did not. Three weeks after HZ onset, gpELISA titers were highest in those with more severe HZ and were slightly increased in placebo recipients (compared with zoster vaccine recipients) and in older individuals. VZV CMI responses to HZ were similar in zoster vaccine and placebo recipients and were not affected by demographic characteristics or antiviral therapy, except for responder cell frequency at HZ onset, which decreased with age. When responses to zoster vaccine and HZ could be compared, VZV CMI values were similar, but antibody titers were lower ConclusionsHigher VZV CMI at HZ onset was associated with reduced HZ severity and less postherpetic neuralgia. Higher antibody titers were associated with increased HZ severity and occurrence of postherpetic neuralgia. HZ and zoster vaccine generated comparable VZV CMI PMID:19712037

Childhood herpes zoster: a clustering of ten cases.

PubMed

Prabhu, Smitha; Sripathi, H; Gupta, Sanjeev; Prabhu, Mukyaprana

2009-01-01

Herpes zoster occurs due to reactivation of the latent varicella zoster virus and is usually a disease of the elderly. Childhood herpes zoster is believed to be rare, though recent studies suggest increasing incidence in children. Here we report ten cases of childhood herpes zoster, seven of which occurred within a short span of six months, at a tertiary care level hospital in Pokhara, Nepal. Only three of the ten children reported previous history of varicella infection and none was immunized against varicella. Though childhood herpes zoster accounted for less than 1% of the total zoster cases in the past, recent reports show an increase in the number of cases in apparently healthy children. So far, no studies have been done linking childhood herpes zoster with HIV, though there are many studies linking it with other immunocompromised conditions.

Varicella-Zoster Virus in Perth, Western Australia: Seasonality and Reactivation.

PubMed

Korostil, Igor A; Regan, David G

2016-01-01

Identification of the factors affecting reactivation of varicella-zoster virus (VZV) largely remains an open question. Exposure to solar ultra violet (UV) radiation is speculated to facilitate reactivation. Should the role of UV in reactivation be significant, VZV reactivation patterns would generally be expected to be synchronous with seasonal UV profiles in temperate climates. We analysed age and gender specific VZV notification time series data from Perth, Western Australia (WA). This city has more daily sunshine hours than any other major Australian city. Using the cosinor and generalized linear models, we tested these data for seasonality and correlation with UV and temperature. We established significant seasonality of varicella notifications and showed that while herpes-zoster (HZ) was not seasonal it had a more stable seasonal component in males over 60 than in any other subpopulation tested. We also detected significant association between HZ notifications and UV for the entire Perth population as well as for females and males separately. In most cases, temperature proved to be a significant factor as well. Our findings suggest that UV radiation may be important for VZV reactivation, under the assumption that notification data represent an acceptably accurate qualitative measure of true VZV incidence.

Identification and functional analysis of the BIM interactome; new clues on its possible involvement in Epstein-Barr Virus-associated diseases.

PubMed

Rouka, Erasmia; Kyriakou, Despoina

2015-12-01

Epigenetic deregulation is a common feature in the pathogenesis of Epstein-Barr Virus (EBV)-related lymphomas and carcinomas. Previous studies have demonstrated a strong association between EBV latency in B-cells and epigenetic silencing of the tumor suppressor gene BIM. This study aimed to the construction and functional analysis of the BIM interactome in order to identify novel host genes that may be targeted by EBV. Fifty-nine unique interactors were found to compose the BIM gene network. Ontological analysis at the pathway level highlighted infectious diseases along with neuropathologies. These results underline the possible interplay between the BIM interactome and EBV-associated disorders.

Update on herpes zoster vaccination

PubMed Central

Shapiro, Marla; Kvern, Brent; Watson, Peter; Guenther, Lyn; McElhaney, Janet; McGeer, Allison

2011-01-01

Abstract Objective To answer frequently asked questions surrounding the use of the new herpes zoster (HZ) vaccine. Sources of information Published results of clinical trials and other studies, recommendations from the Canadian National Advisory Committee on Immunization, and the US Advisory Committee on Immunization Practices; data were also obtained from the vaccine’s Health Canada–approved product monograph. Main message Herpes zoster results from reactivation of the varicella-zoster virus; postherpetic neuralgia (PHN) is its most common and serious complication. The incidence of PHN after HZ is directly related to age, with 50% of affected individuals older than 60 years experiencing persistent and unrelieved pain. The live virus HZ vaccine reduces the incidence of HZ by about 50% and the occurrence of PHN by two-thirds, with vaccinated individuals experiencing attenuated or shortened symptoms. The vaccine is contraindicated in many immunocompromised patients and might not be effective in patients taking antiviral medications active against the HZ virus. Physicians should be aware of the different recommendations for these groups. Conclusion The HZ vaccine is a safe and effective preventive measure for reducing the overall burden and severity of HZ in older adults. The vaccine appears to be cost-effective when administered to adults aged 60 years and older. PMID:21998225

Keratitis in association with herpes zoster and varicella vaccines.

PubMed

Grillo, A P; Fraunfelder, F W

2017-07-01

The objective of this review was to collect reports of keratitis in association with herpes zoster virus (HZV) or varicella zoster virus (VZV) vaccines. HZV vaccination is intended for at-risk adult populations and VZV vaccination is intended for all pediatric patients. We reviewed the literature and reports of keratitis in association with herpes zoster or varicella vaccine from the National Registry of Drug-Induced Ocular Side Effects and the World Health Organization. Twenty-four cases of unilateral keratitis in association with VZV vaccines were collected from the adverse reaction databases and literature. In most cases, the onset of keratitis occurred within days of vaccination and resolved with topical steroid eye drops and oral acyclovir. Data suggest that keratitis in association with herpes zoster or varicella vaccine is rare, is usually self-limited or resolves with treatment. The mechanism may be the persistence of viral antigens in the cornea after VZV vaccination or herpes zoster ophthalmicus. This reaction is probable, given the plausible biological mechanism, the temporal relationship between vaccination and keratitis, and overall patterns of presentation after vaccination. Copyright 2017 Clarivate Analytics.

Vaccines for preventing herpes zoster in older adults.

PubMed

Gagliardi, Anna M Z; Gomes Silva, Brenda Nazaré; Torloni, Maria R; Soares, Bernardo G O

2012-10-17

Herpes zoster or, as it is commonly called, 'shingles' is a neurocutaneous disease characterised by the reactivation of varicella zoster virus (VZV), the virus that causes chickenpox, which is latent in the dorsal spinal ganglia when immunity to VZV declines. It is an extremely painful condition which can often last for many weeks or months, impairing the patient's quality of life. The natural aging process is associated with a reduction of cellular immunity which predisposes to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production, therefore avoiding viral reactivation. A herpes zoster vaccine with an active virus has been approved for clinical use among older adults by the Food and Drug Administration and has been tested in large populations. To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. We searched the following sources for relevant studies: CENTRAL 2012, Issue 7, MEDLINE (1948 to July week 1, 2012), EMBASE (2010 to July 2012), LILACS (1982 to July 2012) and CINAHL (1981 to July 2012). We also reviewed reference lists of identified trials and reviews for additional studies. Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). Two review authors independently collected and analysed data using a data extraction form. They also carried out an assessment of risk of bias. We identified eight RCTs with a total of 52,269 participants. Three studies were classified at low risk of bias. The main outcomes on effectiveness and safety were extracted from one clinical trial with a low risk of bias. Four studies compared zoster vaccine versus placebo; one study compared high-potency zoster vaccine versus low-potency zoster vaccine; one study compared refrigerated zoster vaccine versus frozen zoster vaccine; one study compared live zoster vaccine versus inactivated

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

PubMed Central

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

2015-01-01

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

Vaccines for preventing herpes zoster in older adults.

PubMed

Gagliardi, Anna M Z; Andriolo, Brenda N G; Torloni, Maria R; Soares, Bernardo G O

2016-03-03

Herpes zoster, also known as 'shingles', is a neurocutaneous disease characterised by the reactivation of the latent varicella zoster virus (VZV), the virus that causes chickenpox when immunity to VZV declines. It is an extremely painful condition that can last many weeks or months and it can significantly compromise the quality of life of affected individuals. The natural process of aging is associated with a reduction in cellular immunity and this predisposes older people to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production avoiding viral reactivation. The Food and Drug Administration has approved a herpes zoster vaccine with an attenuated active virus for clinical use among older adults, which has been tested in large populations. A new adjuvanted recombinant VZV subunit zoster vaccine has also been tested. It consists of recombinant VZV glycoprotein E and a liposome-based AS01B adjuvant system. This new vaccine is not yet available for clinical use. To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. For this 2015 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE (1948 to the 3rd week of October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and LILACS (1982 to October 2015). Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). Two review authors independently collected and analysed data using a data extraction form. They also performed 'Risk of bias' assessment. We identified 13 studies involving 69,916 participants. The largest study included 38,546 participants. All studies were conducted in high-income countries and included only healthy Caucasian individuals ≥ 60 years of age without immunosuppressive comorbidities. Ten studies used live attenuated varicella zoster virus (VZV

Bilateral Retrobulbar Optic Neuritis Caused by Varicella Zoster Virus in a Patient with AIDS

PubMed Central

Duda, Jose F.; Castro, Jose G.

2015-01-01

Aims To report on a case of bilateral retrobulbar optic neuritis in a patient with acquired immune deficiency syndrome (AIDS) caused by varicella-zoster virus (VZV); and to review the literature focusing on: cases reported, epidemiology, pathophysiology, diagnosis and treatment. Presentation of Case A 38-year-old woman with AIDS presented with a 10-day history of progressive bilateral visual loss and ocular pain. She had bilateral dilated pupils with no light perception; the fundoscopic examination was normal. Facial herpes zoster lesions appeared on the second day of hospitalization Magnetic resonance imaging (MRI) findings were compatible with a bilateral optic neuritis; the cerebrospinal fluid (CSF) showed pleocytosis, increased proteins and a positive VZV-DNA PCR. She was treated with intravenous acyclovir and corticosteroids and was able, when discharged 2 weeks after admission, to carry out activities of daily living. Discussion VZV retrobulbar optic neuritis has previously been reported in 12 patients with AIDS, more than half of the cases had concomitant herpes zoster and an associated retinopathy. A positive VZV-DNA in the CSF is indicative of VZV infection, initial use of intravenous acyclovir is recommended, and the concomitant use of corticosteroids would be a prudent choice; the duration of antiviral therapy remains undefined. Conclusion VZV retrobulbar optic neuritis in AIDS patients can occur with or without herpes zoster. It is a sight-threatening infectious and inflammatory process requiring the advice of specialists in infectious diseases, ophthalmology, neurology and viral microbiology. PMID:26740936

Outer nuclear membrane fusion of adjacent nuclei in varicella-zoster virus-induced syncytia.

PubMed

Wang, Wei; Yang, Lianwei; Huang, Xiumin; Fu, Wenkun; Pan, Dequan; Cai, Linli; Ye, Jianghui; Liu, Jian; Xia, Ningshao; Cheng, Tong; Zhu, Hua

2017-12-01

Syncytia formation has been considered important for cell-to-cell spread and pathogenesis of many viruses. As a syncytium forms, individual nuclei often congregate together, allowing close contact of nuclear membranes and possibly fusion to occur. However, there is currently no reported evidence of nuclear membrane fusion between adjacent nuclei in wild-type virus-induced syncytia. Varicella-zoster virus (VZV) is one typical syncytia-inducing virus that causes chickenpox and shingles in humans. Here, we report, for the first time, an interesting observation of apparent fusion of the outer nuclear membranes from juxtaposed nuclei that comprise VZV syncytia both in ARPE-19 human epithelial cells in vitro and in human skin xenografts in the SCID-hu mouse model in vivo. This work reveals a novel aspect of VZV-related cytopathic effect in the context of multinucleated syncytia. Additionally, the information provided by this study could be helpful for future studies on interactions of viruses with host cell nuclei. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of neutralizing epitopes of varicella-zoster virus glycoprotein H.

PubMed

Akahori, Yasushi; Suzuki, Kazuhiro; Daikoku, Tohru; Iwai, Masae; Yoshida, Yoshihiro; Asano, Yoshizo; Kurosawa, Yoshikazu; Shiraki, Kimiyasu

2009-02-01

Varicella-zoster virus (VZV) glycoprotein H (gH) is the major neutralization target of VZV, and its neutralizing epitope is conformational. Ten neutralizing human monoclonal antibodies to gH were used to map the epitopes by immunohistochemical analysis and were categorized into seven epitope groups. The combinational neutralization efficacy of two epitope groups was not synergistic. Each epitope was partially or completely resistant to concanavalin A blocking of the glycomoiety of gH, and their antibodies inhibited the cell-to-cell spread of infection. The neutralization epitope comprised at least seven independent protein portions of gH that served as the target to inhibit cell-to-cell spread.

Concurrent detection of herpes simplex and varicella-zoster viruses by polymerase chain reaction from the same anatomic location.

PubMed

Dhiman, Neelam; Wright, Patricia A; Espy, Mark J; Schneider, Susan K; Smith, Thomas F; Pritt, Bobbi S

2011-08-01

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) may cause latent infection of the same peripheral nerve ganglia. However, there are no large studies addressing the frequency of concurrent HSV/VZV PCR positivity from the same anatomic location. In an eight-year retrospective study, we observed 1.3% dual positivity from dermal, genital, and oral mucosal sources. Copyright © 2011 Elsevier Inc. All rights reserved.

Herpes zoster: A clinicocytopathological insight.

PubMed

Shah, Snehal; Singaraju, Sasidhar; Einstein, A; Sharma, Ashish

2016-01-01

Herpes zoster or shingles is reactivation of the varicella zoster virus that had entered the cutaneous nerve endings during an earlier episode of chicken pox traveled to the dorsal root ganglia and remained in a latent form. This condition is characterized by occurrence of multiple, painful, unilateral vesicles and ulceration which shows a typical single dermatome involvement. In this case report, we present a patient with herpes zoster involving the mandibular division of the trigeminal nerve, with unilateral vesicles over the right side of lower third of face along the trigeminal nerve tract, with intraoral involvement of buccal mucosa, labial mucosa and the tongue of the same side. Cytopathology revealed classic features of herpes infection including inclusion bodies, perinuclear halo and multinucleated cells.

Varicella-Zoster Virus in Perth, Western Australia: Seasonality and Reactivation

PubMed Central

Korostil, Igor A.; Regan, David G.

2016-01-01

Background Identification of the factors affecting reactivation of varicella-zoster virus (VZV) largely remains an open question. Exposure to solar ultra violet (UV) radiation is speculated to facilitate reactivation. Should the role of UV in reactivation be significant, VZV reactivation patterns would generally be expected to be synchronous with seasonal UV profiles in temperate climates. Methods We analysed age and gender specific VZV notification time series data from Perth, Western Australia (WA). This city has more daily sunshine hours than any other major Australian city. Using the cosinor and generalized linear models, we tested these data for seasonality and correlation with UV and temperature. Results We established significant seasonality of varicella notifications and showed that while herpes-zoster (HZ) was not seasonal it had a more stable seasonal component in males over 60 than in any other subpopulation tested. We also detected significant association between HZ notifications and UV for the entire Perth population as well as for females and males separately. In most cases, temperature proved to be a significant factor as well. Conclusions Our findings suggest that UV radiation may be important for VZV reactivation, under the assumption that notification data represent an acceptably accurate qualitative measure of true VZV incidence. PMID:26963841

Varicella and herpes zoster vaccine development: lessons learned.

PubMed

Warren-Gash, Charlotte; Forbes, Harriet; Breuer, Judith

2017-12-01

Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines' efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms.

Varicella and herpes zoster vaccine development: lessons learned

PubMed Central

Warren-Gash, Charlotte; Forbes, Harriet; Breuer, Judith

2017-01-01

ABSTRACT Introduction: Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines’ efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms. PMID:29047317

Varicella-Zoster Virus Gastritis: Case Report and Review of the Literature.

PubMed

Nohr, Erik W; Itani, Doha M; Andrews, Christopher N; Kelly, Margaret M

2017-08-01

We report varicella-zoster virus (VZV) gastritis in a 70-year-old woman postchemotherapy for lymphoma, presenting with abdominal pain, vomiting, and delirium without rash. A gastric biopsy demonstrated viral inclusions but posed a diagnostic challenge as immunohistochemistry for cytomegalovirus and herpes simplex virus were negative, and VZV immunohistochemistry was not available. The patient developed a vesicular rash 7 days after her symptoms began. Molecular testing of the gastric biopsy and a skin swab both confirmed VZV infection. She also had probable involvement of her liver and pancreas based on imaging and serum chemistry, and possible central nervous system involvement. She recovered with appropriate antiviral therapy but later developed a postherpetic neuralgia, and chronic intrahepatic biliary strictures; liver biopsy demonstrated a cholangiopathy of uncertain etiology. A literature review of the pathogenesis, epidemiology and sequelae of VZV infection is included.

Varicella Zoster Virus Necrotizing Retinitis in Two Patients with Idiopathic CD4 Lymphocytopenia.

PubMed

Gupta, Meenakashi; Jardeleza, Maria Stephanie R; Kim, Ivana; Durand, Marlene L; Kim, Leo; Lobo, Ann-Marie

2016-10-01

Progressive outer retinal necrosis (PORN) associated with varicella zoster virus (VZV) is usually diagnosed in HIV positive or immunosuppressed patients. We report two cases of immunocompetent patients with necrotizing viral retinitis found to have idiopathic CD4 lymphocytopenia. Clinical presentation, examination, imaging, and laboratory testing of two patients with VZV retinitis are presented. An HIV negative patient with history of herpes zoster presented with rapid loss of vision and examination consistent with PORN. PCR testing confirmed VZV. Lymphocytopenia was noted with a CD4 count of 25/mm(3). A second HIV negative patient presented with blurred vision and lid swelling and was found to have peripheral VZV retinitis confirmed by PCR. Laboratory workup revealed lymphocytopenia with a CD4 count of 133/mm(3). VZV necrotizing retinitis classic for PORN can occur in HIV negative patients. Idiopathic CD4 lymphocytopenia should be considered healthy patients who develop ocular infections seen in the immunocompromised.

A clinico-epidemiological study of herpes zoster.

PubMed

Aggarwal, S K; Radhakrishnan, S

2016-04-01

Herpes zoster is a common viral infection of skin caused by reactivation of varicella zoster virus infection from the spinal ganglia. The clinico-epidemiological patterns of this disease in an Indian setting required to be studied. A cross sectional study was conducted on all consecutive cases of herpes zoster reporting to the Dermatology Outpatient Department at a Tertiary Care Hospital in Bangalore during a period of one year from 01 Jun 2013 to 31 May 2014. Detailed history, examination, HIV screening and Tzanck smear were carried out in all cases. 84 cases of herpes zoster were seen with a mean age of 30 years. Majority (39%) of cases were seen in the 21-30 year age group. Thoracic segments were involved in 65.4%, cervical in 11.9%, cranial in 11.5%, lumbar in 8.3% and sacral segments in 3.5%. 63% of cases had zoster associated pain. One case had motor involvement.3.57% of the patients were HIV positive. This study shows a lower age incidence of herpes zoster HIV positivity and zoster associated pain as compared to other studies. The pattern of segmental involvement in herpes zoster seen in this study was similar to other studies.

The association of Varicella zoster virus reactivation with Bell's palsy in children.

PubMed

Abdel-Aziz, Mosaad; Azab, Noha A; Khalifa, Badwy; Rashed, Mohammed; Naguib, Nader

2015-03-01

Bell's palsy is considered the most common cause of facial nerve paralysis in children. Although different theories have been postulated for its diagnosis, reactivation of the Varicella zoster virus (VZV) has been implicated as one of the causes of Bell's palsy. The aim of the study was to evaluate the association of Varicella-zoster virus infection with Bell's palsy and its outcome in children. A total of 30 children with Bell's palsy were recruited and were assayed for evidence of VZV infection. The severity of facial nerve dysfunction and the recovery rate were evaluated according to House-Brackmann Facial Nerve Grading Scale (HB FGS). Paired whole blood samples from all patients were obtained at their initial visit and 3 weeks later, and serum samples were analyzed for VZV IgG and IgM antibodies using ELISA. A significantly higher percentage of Bell's palsy patients were seropositive for VZV IgM antibodies than controls (36.6% of patients vs 10% of controls) while for VZV IgG antibodies the difference was statistically nonsignificant. HB FGS in Bell's palsy patients with serologic evidence of VZV recent infection or reactivation showed a statistiacally significant less cure rate than other patients. VZV reactivation may be an important cause of acute peripheral facial paralysis in children. The appropriate diagnosis of VZV reactivation should be done to improve the outcome and the cure rate by the early use of antiviral treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Poor recall of prior exposure to varicella zoster, rubella, measles, or mumps in patients with IBD.

PubMed

Naganuma, Makoto; Nagahori, Masakazu; Fujii, Toshimitsu; Morio, Junko; Saito, Eiko; Watanabe, Mamoru

2013-02-01

Few studies have measured the levels of antibodies specific for measles, mumps, rubella, and varicella zoster/chickenpox viruses in inflammatory bowel disease (IBD) patients undergoing treatment with immunomodulators/biologics. We prospectively recruited 139 IBD outpatients. Enzyme-linked immunosorbent assays were used as the serological tests for measles, mumps, rubella, and varicella zoster. We defined anti-rubella IgG < 10 IU/mL, anti-measles IgG < 16 IU/mL, and anti-mumps/varicella zoster IgG <4 IU/mL as seronegative for viruses. We also asked participants about past immunizations against or infections with measles, mumps, rubella, and varicella zoster viruses. The proportion of patients with seronegative levels of antibodies specific for varicella zoster, rubella, measles, and mumps viruses was 5%, 30%, 34%, and 37%, respectively. Approximately 40% of the IBD patients did not remember whether they had previously been infected with any of the viruses, and almost one-third of the patients could not remember whether they had previously been vaccinated. Almost 30% of the patients with a past history of rubella or measles did not have seropositive antibody levels. A total of 54% of the patients being treated with immunosuppressant displayed seronegative levels of antibodies specific for at least one of the viruses. Many IBD patients were unaware of whether they had previously been vaccinated against or infected with the viruses causing varicella zoster, rubella, measles, or mumps. Therefore, measuring the current levels of antibodies specific for such viruses is useful for determining whether patients have seropositive antibody levels before immunomodulators/biologics are used for therapy.

Zoster vaccine live for the prevention of shingles in the elderly patient

PubMed Central

Zussman, Jamie; Young, Lorraine

2008-01-01

Shingles, also known as herpes zoster, is a common disease in the elderly population that is caused by reactivation of latent varicella zoster virus. Its manifestations and complications can lead to significant short- and long-term morbidity. In 2006, the United States Food and Drug Administration approved Zoster Vaccine Live (Zostavax®) for the prevention of herpes zoster in immunocompetent adults age 60 and over. The approval was based on the results of a large, multi-center clinical trial, the Shingles Prevention Study. This study showed that vaccination significantly decreased shingles incidence, burden of illness due to disease, and the development of, and severity of postherpetic neuralgia. This review offers an overview of varicella zoster virus infection and complications, a summary of the Shingles Prevention Study, and a critical analysis designed to aid the practicing physician who has questions about vaccine administration. PMID:18686747

The role of solar ultraviolet irradiation in zoster.

PubMed Central

Zak-Prelich, M.; Borkowski, J. L.; Alexander, F.; Norval, M.

2002-01-01

Ultraviolet radiation (UVR) suppresses many aspects of cell-mediated immunity but it is uncertain whether solar UV exposure alters resistance to human infectious diseases. Varicella-zoster virus (VZV) causes varicella (chickenpox) and can reactivate from latency to cause zoster (shingles). The monthly incidence of chickenpox and zoster in a defined Polish population over 2 years was recorded and ground level solar UV was measured daily. There was a significant seasonality of UVR. Evidence of seasonal variation was found for all zoster cases and for zoster in males, with the lowest number of cases in the winter. The number of zoster cases with lesions occurring on exposed body sites (the face) demonstrated highly significant seasonality with a peak in July/August. Seasonal models for UVR and zoster cases showed similar temporal patterns. By contrast, for varicella, the maximum number of cases was found in March and the minimum in August/September, probably explained by the respiratory spread of VZV. It is tempting to speculate that the increase in solar UVR in the summer could induce suppression of cellular immunity, thus contributing to the corresponding rise in the incidence of zoster. PMID:12558343

The role of solar ultraviolet irradiation in zoster.

PubMed

Zak-Prelich, M; Borkowski, J L; Alexander, F; Norval, M

2002-12-01

Ultraviolet radiation (UVR) suppresses many aspects of cell-mediated immunity but it is uncertain whether solar UV exposure alters resistance to human infectious diseases. Varicella-zoster virus (VZV) causes varicella (chickenpox) and can reactivate from latency to cause zoster (shingles). The monthly incidence of chickenpox and zoster in a defined Polish population over 2 years was recorded and ground level solar UV was measured daily. There was a significant seasonality of UVR. Evidence of seasonal variation was found for all zoster cases and for zoster in males, with the lowest number of cases in the winter. The number of zoster cases with lesions occurring on exposed body sites (the face) demonstrated highly significant seasonality with a peak in July/August. Seasonal models for UVR and zoster cases showed similar temporal patterns. By contrast, for varicella, the maximum number of cases was found in March and the minimum in August/September, probably explained by the respiratory spread of VZV. It is tempting to speculate that the increase in solar UVR in the summer could induce suppression of cellular immunity, thus contributing to the corresponding rise in the incidence of zoster.

Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine.

PubMed

James, Stephanie F; Chahine, Elias B; Sucher, Allana J; Hanna, Cassandra

2018-02-01

To review the immunogenicity, efficacy, and safety of the herpes zoster subunit vaccine (HZ/su) for use in adult patients for the prevention of shingles. A literature search through PubMed was conducted (June 2008 to October 2017) using the terms shingles vaccine and varicella zoster virus. References from retrieved articles and the prescribing information were also reviewed for any additional material. The literature search was limited to human studies published in English. Randomized controlled, multicenter trials were reviewed and included to evaluate the safety and efficacy of HZ/su. Literature on the epidemiology and pathology of herpes zoster virus infections and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed. HZ/su is a new adjuvanted recombinant vaccine approved by the Food and Drug Administration for the prevention of herpes zoster in adults 50 years of age and older. HZ/su significantly reduced the risk of developing herpes zoster by more than 90% as compared with placebo and displayed a comparable adverse effect profile. The most common local adverse events were injection site pain, redness, and swelling, and the most common systemic adverse events were myalgia, fatigue, and headache. The ACIP recommends the routine use of HZ/su as the preferred vaccine for the prevention of herpes zoster in immunocompetent adults 50 years of age and older. Based on published immunogenicity, efficacy, and safety data, as well as the recent recommendations by the ACIP, HZ/su should be included on both hospital and community pharmacy formularies and recommended to all immunocompetent patients older than 50 years to prevent herpes zoster.

Herpes zoster-associated acute urinary retention in immunocompetent patient*

PubMed Central

Marques, Silvio Alencar; Hortense, Juliana

2014-01-01

Herpes zoster-associated urinary retention is an uncommon event related to virus infection of the S2-S4 dermatome. The possible major reasons are ipsilateral hemicystitis, neuritis-induced or myelitis-associated virus infection. We report a case of a 65-year-old immunocompetent female patient who presented an acute urinary retention after four days under treatment with valacyclovir for gluteal herpes zoster. The patient had to use a vesical catheter, was treated with antibiotics and corticosteroids and fully recovered after eight weeks. PMID:25387508

Safety, humoral and cell-mediated immune responses to herpes zoster vaccine in subjects with diabetes mellitus.

PubMed

Hata, Atsuko; Inoue, Fukue; Yamasaki, Midori; Fujikawa, Jun; Kawasaki, Yukiko; Hamamoto, Yoshiyuki; Honjo, Sachiko; Moriishi, Eiko; Mori, Yasuko; Koshiyama, Hiroyuki

2013-09-01

To evaluate varicella zoster virus-specific cell-mediated immunity and humoral immunogenicity against the herpes zoster vaccine, which is licensed as the Live Varicella Vaccine (Oka Strain) in Japan, in elderly people with or without diabetes mellitus. A pilot study was conducted between May 2010 and November 2010 at Kitano Hospital, a general hospital in the city of Osaka in Japan. A varicella skin test, interferon-gamma enzyme-linked immunospot assay and immunoadherence hemagglutination tests were performed 0, 3, and 6 months after vaccination. Vaccine safety was also assessed using questionnaires for 42 days and development of zoster during the one-year observational period. We enrolled 10 healthy volunteers and 10 patients with diabetes mellitus aged 60-70 years. The live herpes zoster vaccine boosted virus-specific, cell-mediated and humoral immunity between elderly people, with or without diabetes. Moreover, no systemic adverse reaction was found. None of the study participants developed herpes zoster. The live herpes zoster vaccine was used safely. It effectively enhanced specific immunity to varicella zoster virus in older people with or without diabetes mellitus. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The Uncommon Localization of Herpes Zoster

PubMed Central

Cukic, Vesna

2016-01-01

Introduction: Herpes zoster is an acute, cutaneous viral infection caused by the reactivation of varicella-zoster virus (VZV) that is the cause of varicella. It is an acute neurological disease which can often lead to serious postherpetic neuralgia (PHN). Different nerves can be included with the skin rash in the area of its enervation especially cranial nerves (CV) and intercostal nerves. Case report: In this report we present a patient with herpes zoster which involved ulnar nerve with skin rash in the region of ulnar innervations in women with no disease previously diagnosed. The failure of her immune system may be explained by great emotional stress and overwork she had been exposed to with neglecting proper nutrition in that period. Conclusion: Herpes zoster may involve any nerve with characteristic skin rash in the area of its innervations, and failure in immune system which leads reactivation of VZV may be caused by other factors besides the underlying illness. PMID:26980938

A 70-year-old woman with shingles: review of herpes zoster.

PubMed

Whitley, Richard J

2009-07-01

Herpes zoster is a common late complication of varicella-zoster virus exposure and can be further complicated by postherpetic neuralgia. Ms A is a 70-year-old woman with shingles and Ramsay-Hunt syndrome who presented to the emergency department with a few days of earache followed by pain in the back of her head. Using her case as a springboard, the diagnosis, natural history, and treatment of herpes zoster and postherpetic neuralgia in immunocompetent older adults are reviewed, in addition to the effectiveness of the herpes zoster vaccine.

Varicella zoster virus-associated morbidity and mortality in Africa - a systematic review.

PubMed

Hussey, Hannah; Abdullahi, Leila; Collins, Jamie; Muloiwa, Rudzani; Hussey, Gregory; Kagina, Benjamin

2017-11-14

Varicella zoster virus (VZV) causes varicella and herpes zoster. These vaccine preventable diseases are common globally. Most available data on VZV epidemiology are from industrialised temperate countries and cannot be used to guide decisions on the immunization policy against VZV in Africa. This systematic review aims to review the published data on VZV morbidity and mortality in Africa. All published studies conducted in Africa from 1974 to 2015 were eligible. Eligible studies must have reported any VZV epidemiological measure (incidence, prevalence, hospitalization rate and mortality rate). For inclusion in the review, studies must have used a defined VZV case definition, be it clinical or laboratory-based. Twenty articles from 13 African countries were included in the review. Most included studies were cross-sectional, conducted on hospitalized patients, and half of the studies used varying serological methods for diagnosis. VZV seroprevalence was very high among adults. Limited data on VZV seroprevalence in children showed very low seropositivity to anti-VZV antibodies. Co-morbidity with VZV was common. There is lack of quality data that could be used to develop VZV control programmes, including vaccination, in Africa. PROSPERO 2015: CRD42015026144 .

Species-specific differentiation of variola, monkeypox, and varicella-zoster viruses by multiplex real-time PCR assay.

PubMed

Maksyutov, Rinat A; Gavrilova, Elena V; Shchelkunov, Sergei N

2016-10-01

A method of one-stage rapid detection and differentiation of epidemiologically important variola virus (VARV), monkeypox virus (MPXV), and varicella-zoster virus (VZV) utilizing multiplex real-time TaqMan PCR assay was developed. Four hybridization probes with various fluorescent dyes and the corresponding fluorescence quenchers were simultaneously used for the assay. The hybridization probes specific for the VARV sequence contained FAM/BHQ1 as a dye/quencher pair; MPXV-specific, JOE/BHQ1; VZV-specific, TAMRA/BHQ2; and internal control-specific, Cy5/BHQ3. The specificity and sensitivity of the developed method were assessed by analyzing DNA of 32 strains belonging to orthopoxvirus and herpesvirus species. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical and immunologic features of recurrent herpes zoster (HZ).

PubMed

Nakamura, Yuki; Miyagawa, Fumi; Okazaki, Aiko; Okuno, Yoshinobu; Mori, Yasuko; Iso, Hiroyasu; Yamanishi, Koichi; Asada, Hideo

2016-11-01

Recurrent herpes zoster (HZ) is thought to be rare, but there have been few large-scale studies of recurrent HZ. We conducted a large-scale prospective cohort study to characterize recurrent HZ. We examined 12,522 participants aged 50 years or older in Shozu County and followed them up for 3 years. We compared the incidence of HZ and postherpetic neuralgia, severity of skin lesions and acute pain, cell-mediated immunity, and varicella-zoster virus-specific antibody titer between primary and recurrent HZ. A total of 401 participants developed HZ: 341 with primary HZ and 60 with recurrent HZ. Skin lesions and acute pain were significantly milder and the incidence of postherpetic neuralgia was lower in patients aged 50 to 79 years with recurrent HZ than in those with primary HZ. Varicella-zoster virus skin test induced a stronger reaction in patients aged 50 to 79 years with recurrent HZ than in those with primary HZ. Information on previous HZ episodes was self-reported by participants, so it could not be confirmed that they actually had a history of HZ. Recurrent HZ was associated with milder clinical symptoms than primary HZ, probably because of stronger varicella-zoster virus-specific cell-mediated immunity in the patients with recurrence. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Inhibition of Bim Enhances Replication of Varicella-Zoster Virus and Delays Plaque Formation in Virus-Infected Cells

PubMed Central

Liu, XueQiao

2014-01-01

Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication. PMID:24227856

Epidemiology, treatment and prevention of herpes zoster: A comprehensive review.

PubMed

Koshy, Elsam; Mengting, Lu; Kumar, Hanasha; Jianbo, Wu

2018-01-01

Herpes zoster is a major health burden that can affect individuals of any age. It is seen more commonly among individuals aged ≥50 years, those with immunocompromised status, and those on immunosuppressant drugs. It is caused by a reactivation of varicella zoster virus infection. Cell-mediated immunity plays a role in this reactivation. Fever, pain, and itch are common symptoms before the onset of rash. Post-herpetic neuralgia is the most common complication associated with herpes zoster. Risk factors and complications associated with herpes zoster depend on the age, immune status, and the time of initializing treatment. Routine vaccination for individuals over 60 years has shown considerable effect in terms of reducing the incidence of herpes zoster and post-herpetic neuralgia. Treatment with antiviral drugs and analgesics within 72 hours of rash onset has been shown to reduce severity and complications associated with herpes zoster and post-herpetic neuralgia. This study mainly focuses on herpes zoster using articles and reviews from PubMed, Embase, Cochrane library, and a manual search from Google Scholar. We cover the incidence of herpes zoster, gender distribution, seasonal and regional distribution of herpes zoster, incidence of herpes zoster among immunocompromised individuals, incidence of post-herpetic neuralgia following a zoster infection, complications, management, and prevention of herpes zoster and post-herpetic neuralgia.

Sacral Herpes Zoster Associated with Voiding Dysfunction in a Young Patient with Scrub Typhus.

PubMed

Hur, Jian

2015-06-01

When a patient presents with acute voiding dysfunction without a typical skin rash, it may be difficult to make a diagnosis of herpes zoster. Here, we present a case of scrub typhus in a 25-year-old man with the complication of urinary dysfunction. The patient complained of loss of urinary voiding sensation and constipation. After eight days, he had typical herpes zoster eruptions on the sacral dermatomes and hypalgesia of the S1-S5 dermatomes. No cases of dual infection with varicella zoster virus and Orientia tsutsugamushi were found in the literature. In the described case, scrub typhus probably induced sufficient stress to reactivate the varicella zoster virus. Early recognition of this problem is imperative for prompt and appropriate management, as misdiagnosis can lead to long-term urinary dysfunction. It is important that a diagnosis of herpes zoster be considered, especially in patients with sudden onset urinary retention.

Epidemiological Study on the Incidence of Herpes Zoster in Nearby Cheonan

PubMed Central

Jung, Ho Soon; Kang, Jin Ku

2015-01-01

Background Herpes Zoster is a disease that occurs after the virus is reactivated due to infection of the varicella virus in childhood. Risk factors are advanced age, malignant neoplasm, organ transplantation, immunosuppressive agents taking are known. The purpose of this study was to investigate the relationship between the seasonal effect and other risk factors on the incidence of herpes zoster. Methods The medical records of 1,105 patients admitted to the outpatient diagnosed with herpes zoster were retrospectively examined. The patients' sex, age, dermatome, onset, underlying disease, residential areas were collected. Results The incidence of women outnumbered men and increased for those above the age of 50. The number of occurrences of herpes zoster patients was higher in the spring and summer than in winter. Unlike men, women had the most frequent outbreaks in March. The most common occurrence of dermatome is in the thoracic region. The number of occurrence was similar on the left as the right. Conclusions In this study, herpes zoster occurs more often in women than in men and more frequently occurs in women in the spring and summer. PMID:26175879

[Immunization against varicella and zoster].

PubMed

Floret, Daniel

2007-06-01

Two vaccines against varicella-zoster virus are available in France. These live attenuated vaccines are derived from the Oka strain used in Japan since 1974. They are indicated for healthy subjects from 12 months of age, at a dose of one injection until 12 years of age, and two injections 4-8 weeks apart for older children and adults. Seroconversion occurs in 95% of cases and the antibodies persist beyond 5 years. Clinical efficacy is about 85% against all forms of varicella and nearly 100% against severe forms. Post-exposure vaccination within 3 days may also prevent the disease. A universal immunization program against varicella was implemented in the USA in 1995. Now, with vaccine coverage at about 80%, the incidence of the disease has been reduced by 85%, with the largest decrease in 1- to 4-year-olds. Tolerability is generally good, with only mild reactions at the injection site and moderate fever The length of protection is not yet known. A two-dose schedule seems advisable to avoid breakthrough varicella, which occurs in 4% of vaccinees each year. Insufficient coverage is expected to lead to later disease onset, with more severe cases in adolescents and adults. Universal immunization could also increase the incidence of zoster. These problems indeed seem to be emerging in the United States. France has adopted restrictive guidelines on VZV vaccination, but they are expected to be revised when the combined MMR-V vaccine becomes available. Zoster vaccine, prepared with the same strain but at a higher concentration, has moderate efficacy on zoster and on post-zoster neuralgia in patients over 70. This vaccine is not yet recommended in France, because the length of protection is not known and there is a potential risk of delaying the occurrence of zoster and, thus, of increasing the risk of post zoster neuralgia.

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent Varicella-Zoster Virus Infection

PubMed Central

Goodwin, Thomas J.; McCarthy, Maureen; Osterrieder, Nikolaus; Cohrs, Randall J.; Kaufer, Benedikt B.

2013-01-01

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells. PMID:23935496

Mitochondrial Haplogroups as a Risk Factor for Herpes Zoster.

PubMed

Levinson, Rebecca T; Hulgan, Todd; Kalams, Spyros A; Fessel, Joshua P; Samuels, David C

2016-10-01

Background.  Herpes zoster, or shingles, is a common, painful reactivation of latent varicella zoster virus infection. Understanding host factors that predispose to herpes zoster may permit development of more effective prevention strategies. Our objective was to examine mitochondrial haplogroups as a potential host factor related to herpes zoster incidence. Methods.  Study participants were drawn from BioVU, a deoxyribonucleic acid (DNA) biobank connected to deidentified electronic medical records (EMRs) from Vanderbilt University Medical Center. Our study used 9691 Caucasian individuals with herpes zoster status determined by International Classification of Diseases, Ninth Revision codes 053-053.9. Cases and controls were matched on sex and date of birth within 5 years. Mitochondrial haplogroups were defined from mitochondrial DNA variants genotyped on the Illumina 660W or Illumina Infinium Human-Exome Beadchip. Sex and date of birth were extracted from the EMR. Results.  European mitochondrial haplogroup H had a protective association with herpes zoster status (odds ratio [OR] = .82; 95% confidence interval [CI], .71-.94; P = .005), whereas haplogroup clade IWX was a risk factor for herpes zoster status (OR = 1.38; 95% CI, 1.07-1.77; P = .01). Conclusions.  Mitochondrial haplogroup influences herpes zoster risk. Knowledge of a patient's mitochondrial haplogroup could allow for a precision approach to the management of herpes zoster risk through vaccination strategies and management of other modifiable risk factors.

Interactome of the hepatitis C virus: Literature mining with ANDSystem.

PubMed

Saik, Olga V; Ivanisenko, Timofey V; Demenkov, Pavel S; Ivanisenko, Vladimir A

2016-06-15

A study of the molecular genetics mechanisms of host-pathogen interactions is of paramount importance in developing drugs against viral diseases. Currently, the literature contains a huge amount of information that describes interactions between HCV and human proteins. In addition, there are many factual databases that contain experimentally verified data on HCV-host interactions. The sources of such data are the original data along with the data manually extracted from the literature. However, the manual analysis of scientific publications is time consuming and, because of this, databases created with such an approach often do not have complete information. One of the most promising methods to provide actualisation and completeness of information is text mining. Here, with the use of a previously developed method by the authors using ANDSystem, an automated extraction of information on the interactions between HCV and human proteins was conducted. As a data source for the text mining approach, PubMed abstracts and full text articles were used. Additionally, external factual databases were analyzed. On the basis of this analysis, a special version of ANDSystem, extended with the HCV interactome, was created. The HCV interactome contains information about the interactions between 969 human and 11 HCV proteins. Among the 969 proteins, 153 'new' proteins were found not previously referred to in any external databases of protein-protein interactions for HCV-host interactions. Thus, the extended ANDSystem possesses a more comprehensive detailing of HCV-host interactions versus other existing databases. It was interesting that HCV proteins more preferably interact with human proteins that were already involved in a large number of protein-protein interactions as well as those associated with many diseases. Among human proteins of the HCV interactome, there were a large number of proteins regulated by microRNAs. It turned out that the results obtained for protein

Close correlation of herpes zoster-induced voiding dysfunction with severity of zoster-related pain: A single faculty retrospective study.

PubMed

Fujii, Mizue; Takahashi, Ichiro; Honma, Masaru; Ishida-Yamamoto, Akemi

2015-11-01

Herpes zoster (HZ), a common vesiculo-erythematous skin disease associated with reactivation of varicella zoster virus in the cranial nerve, dorsal root, and autonomic ganglia, is accompanied by several related symptoms represented by postherpetic neuralgia. Among them, involvement of vesicorectal dysfunction is relatively rare. The vesicorectal symptom can usually be recovered in transient course, but is quite important in terms of impaired quality of life. Male individuals affected with HZ and skin lesions on sacral dermatome have been reported as independent risk factors of zoster-related voiding dysfunction. In this study, urinary symptoms were focused upon and six patients with zoster-related voiding dysfunction at a single faculty of dermatology in Japan from 2009 to 2014 were retrospectively analyzed. All patients showed HZ lesions on the sacral area and the urinary symptom recovered in approximately 2 months (14 days to 7 months). The term of treatment for zoster-associated urinary dysfunction was positively correlated with that for zoster-related pain without significance (r = 0.661, P = 0.153). Average treatment term for pain relief of sacral HZ accompanied by voiding dysfunction (91.3 ± 76.44 days) was significantly longer than that of sacral HZ without urinary symptom (18.9 ± 20.42 days) (P = 0.032). These results suggested that zoster-related voiding dysfunction would mainly be involved in sacral HZ and closely associated with severity of zoster-related pain. Dermatologists should be aware that severe zoster-related pain accompanied by sacral HZ, which is related to prolonged treatment of pain relief, can be a predictive factor of voiding dysfunction. © 2015 Japanese Dermatological Association.

Herpes zoster and the search for an effective vaccine

PubMed Central

Arnold, N.

2016-01-01

Summary Primary infection with varicella zoster virus (VZV), an exclusively human neurotrophic alphaherpsesvirus, results in varicella, known more commonly as chickenpox. Like other alphaherpesviruses, VZV establishes latency in the sensory ganglia and can reactivate to cause herpes zoster (also known as shingles), a painful and debilitating disease, especially in elderly and immunocompromised individuals. The overall incidence of herpes zoster in Europe and the United States is three per 1000 people, but increases sharply after 60 years of age to 10 per 1000 people. Zostavax® is a vaccine approved by the Federal Drug Administration for the prevention of herpes zoster. Unfortunately, this vaccine reduces the incidence of disease by only 51% and the incidence of post‐herpetic neuralgia by 66·5% when administered to those aged 60 and older. Moreover, it is contraindicated for individuals who are immunocompromised or receiving immunosuppressant treatments, although they are at higher risk for herpes zoster compared to immune‐competent older individuals. This paper reviews VZV pathogenesis, host responses and current vaccines available to prevent herpes zoster. PMID:27164323

Sacral Herpes Zoster Associated with Voiding Dysfunction in a Young Patient with Scrub Typhus

PubMed Central

2015-01-01

When a patient presents with acute voiding dysfunction without a typical skin rash, it may be difficult to make a diagnosis of herpes zoster. Here, we present a case of scrub typhus in a 25-year-old man with the complication of urinary dysfunction. The patient complained of loss of urinary voiding sensation and constipation. After eight days, he had typical herpes zoster eruptions on the sacral dermatomes and hypalgesia of the S1-S5 dermatomes. No cases of dual infection with varicella zoster virus and Orientia tsutsugamushi were found in the literature. In the described case, scrub typhus probably induced sufficient stress to reactivate the varicella zoster virus. Early recognition of this problem is imperative for prompt and appropriate management, as misdiagnosis can lead to long-term urinary dysfunction. It is important that a diagnosis of herpes zoster be considered, especially in patients with sudden onset urinary retention. PMID:26157595

Human Embryonic Stem Cell-Derived Neurons Are Highly Permissive for Varicella-Zoster Virus Lytic Infection.

PubMed

Sadaoka, Tomohiko; Schwartz, Cindi L; Rajbhandari, Labchan; Venkatesan, Arun; Cohen, Jeffrey I

2018-01-01

Varicella-zoster virus (VZV) is highly cell associated when grown in culture and has a much higher (4,000- to 20,000-fold increased) particle-to-PFU ratio in vitro than herpes simplex virus (HSV). In contrast, VZV is highly infectious in vivo by airborne transmission. Neurons are major targets for VZV in vivo ; in neurons, the virus can establish latency and reactivate to produce infectious virus. Using neurons derived from human embryonic stem cells (hESC) and cell-free wild-type (WT) VZV, we demonstrated that neurons are nearly 100 times more permissive for WT VZV infection than very-early-passage human embryonic lung cells or MRC-5 diploid human fibroblasts, the cells used for vaccine production or virus isolation. The peak titers achieved after infection were ∼10-fold higher in human neurons than in MRC-5 cells, and the viral genome copy number-to-PFU ratio for VZV in human neurons was 500, compared with 50,000 for MRC-5 cells. Thus, VZV may not necessarily have a higher particle-to-PFU ratio than other herpesviruses; instead, the cells previously used to propagate virus in vitro may have been suboptimal. Furthermore, based on electron microscopy, neurons infected with VZV produced fewer defective or incomplete viral particles than MRC-5 cells. Our data suggest that neurons derived from hESC may have advantages compared to other cells for studies of VZV pathogenesis, for obtaining stocks of virus with high titers, and for isolating VZV from clinical specimens. IMPORTANCE Varicella-zoster virus (VZV) causes chickenpox and shingles. Cell-free VZV has been difficult to obtain, both for in vitro studies and for vaccine production. While numerous cells lines have been tested for their ability to produce high titers of VZV, the number of total virus particles relative to the number of viral particles that can form plaques in culture has been reported to be extremely high relative to that in other viruses. We show that VZV grows to much higher titers in human

Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

PubMed

Hornberger, John; Robertus, Katherine

2006-09-05

The Shingles Prevention Study showed that a varicella-zoster virus (VZV) vaccine administered to adults 60 years of age or older reduced the incidence of herpes zoster from 11.12 to 5.42 cases per 1000 person-years. Median follow-up was 3.1 years, and relative risk reduction was 51.3% (95% CI, 44.2% to 57.6%). To assess the extent to which clinical and cost variables influence the cost-effectiveness of VZV vaccination for preventing herpes zoster in immunocompetent older adults. Decision theoretical model. English-language data published to March 2006 identified from MEDLINE on herpes zoster rates, vaccine effectiveness, quality of life, medical resource use, and unit costs. Immunocompetent adults 60 years of age or older with a history of VZV infection. Lifetime. U.S. societal. Varicella-zoster virus vaccination versus no vaccination. Incremental quality-adjusted survival and cost per quality-adjusted life-year (QALY) gained. By reducing incidence and severity of herpes zoster, vaccination can increase quality-adjusted survival by 0.6 day compared with no vaccination. One scenario in which vaccination costs less than 100,000 dollars per QALY gained is when 1) the unit cost of vaccination is less than 200 dollars, 2) the age at vaccination is less than 70 years, and 3) the duration of vaccine efficacy is more than 30 years. Vaccination would be more cost-effective in "younger" older adults (age 60 to 64 years) than in "older" older adults (age > or =80 years). Longer life expectancy and a higher level of vaccine efficacy offset a lower risk for herpes zoster in the younger group. Other factors influencing cost-effectiveness include quality-of-life adjustments for acute zoster, unit cost of the vaccine, risk for herpes zoster, and duration of vaccine efficacy. The effectiveness of VZV vaccination remains uncertain beyond the median 3.1-year duration of follow-up in the Shingles Prevention Study. Varicella-zoster virus vaccination to prevent herpes zoster in older

Identification and characterization of 20 immunocompetent patients with simultaneous varicella zoster and herpes simplex virus infection.

PubMed

Giehl, K A; Müller-Sander, E; Rottenkolber, M; Degitz, K; Volkenandt, M; Berking, C

2008-06-01

It has been shown that varicella zoster virus (VZV) and herpes simplex virus (HSV) can co-localize to the same sensory ganglion. However, only a few case reports on VZV/HSV co-infections exist. Objective To identify and characterize patients with concurrent VZV and HSV infection at the same body site. In 1718 patients, the presence of VZV and HSV in suspicious skin lesions was investigated by polymerase chain reaction analysis. Clinical characteristics of co-infected patients were compared with matched control patients infected with either VZV or HSV. The data are discussed in the context of an extensive review of the literature. Twenty (1.2%) of 1718 patients were infected with both VZV and HSV at the same body site. The mean age was 54 years (range, 2-83). The clinical diagnosis was zoster in 65%, herpes simplex in 20%, varicella in 10% and erythema multiforme in 5% of cases. The trigeminus region was affected in 60% and the trunk in 25%. Involvement of the head was most commonly associated with a severe course of disease and with older age. Simultaneous VZV/HSV infection is rare but can occur in immunocompetent patients, which is often overlooked. The majority of cases is localized to the trigeminus region and affects elderly people.

Is chickenpox so bad, what do we know about immunity to varicella zoster virus, and what does it tell us about the future?

PubMed

Gershon, Anne A

2017-06-01

Varicella and zoster continue to cause significant morbidity and even mortality in children and adults. Complications include bacterial superinfection, central nervous system manifestations such as meningitis, encephalitis, and cerebellar ataxia, and pain syndromes especially post herpetic neuralgia. Many developed countries but not all, are now administering live attenuated varicella vaccine routinely, with a decrease in the incidence of disease, providing personal and herd immunity. There is some controversy, however, in some countries concerning whether a decrease in the circulation of wild type virus will result in loss of immunity to VZV in persons who have already had varicella. This manuscript reviews the complications of varicella and zoster in detail, the reasons for development of vaccines against these diseases, complications of vaccinations, and mechanisms by which immunity to this virus develops and is maintained. There are strong indications that the best way to control disease and spread of this virus is by vaccination against both. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The Protein Interactome of Mycobacteriophage Giles Predicts Functions for Unknown Proteins.

PubMed

Mehla, Jitender; Dedrick, Rebekah M; Caufield, J Harry; Siefring, Rachel; Mair, Megan; Johnson, Allison; Hatfull, Graham F; Uetz, Peter

2015-08-01

Mycobacteriophages are viruses that infect mycobacterial hosts and are prevalent in the environment. Nearly 700 mycobacteriophage genomes have been completely sequenced, revealing considerable diversity and genetic novelty. Here, we have determined the protein complement of mycobacteriophage Giles by mass spectrometry and mapped its genome-wide protein interactome to help elucidate the roles of its 77 predicted proteins, 50% of which have no known function. About 22,000 individual yeast two-hybrid (Y2H) tests with four different Y2H vectors, followed by filtering and retest screens, resulted in 324 reproducible protein-protein interactions, including 171 (136 nonredundant) high-confidence interactions. The complete set of high-confidence interactions among Giles proteins reveals new mechanistic details and predicts functions for unknown proteins. The Giles interactome is the first for any mycobacteriophage and one of just five known phage interactomes so far. Our results will help in understanding mycobacteriophage biology and aid in development of new genetic and therapeutic tools to understand Mycobacterium tuberculosis. Mycobacterium tuberculosis causes over 9 million new cases of tuberculosis each year. Mycobacteriophages, viruses of mycobacterial hosts, hold considerable potential to understand phage diversity, evolution, and mycobacterial biology, aiding in the development of therapeutic tools to control mycobacterial infections. The mycobacteriophage Giles protein-protein interaction network allows us to predict functions for unknown proteins and shed light on major biological processes in phage biology. For example, Giles gp76, a protein of unknown function, is found to associate with phage packaging and maturation. The functions of mycobacteriophage-derived proteins may suggest novel therapeutic approaches for tuberculosis. Our ORFeome clone set of Giles proteins and the interactome data will be useful resources for phage interactomics. Copyright © 2015

A Real-Time PCR Assay to Identify and Discriminate Among Wild-Type and Vaccine Strains of Varicella-Zoster Virus and Herpes Simplex Virus in Clinical Specimens, and Comparison With the Clinical Diagnoses

PubMed Central

Harbecke, Ruth; Oxman, Michael N.; Arnold, Beth A.; Ip, Charlotte; Johnson, Gary R.; Levin, Myron J.; Gelb, Lawrence D.; Schmader, Kenneth E.; Straus, Stephen E.; Wang, Hui; Wright, Peter F.; Pachucki, Constance T.; Gershon, Anne A.; Arbeit, Robert D.; Davis, Larry E.; Simberkoff, Michael S.; Weinberg, Adriana; Williams, Heather M.; Cheney, Carol; Petrukhin, Luba; Abraham, Katalin G.; Shaw, Alan; Manoff, Susan; Antonello, Joseph M.; Green, Tina; Wang, Yue; Tan, Charles; Keller, Paul M.

2014-01-01

A real-time PCR assay was developed to identify varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA in clinical specimens from subjects with suspected herpes zoster (HZ; shingles). Three sets of primers and probes were used in separate PCR reactions to detect and discriminate among wild-type VZV (VZV-WT), Oka vaccine strain VZV (VZV-Oka), and HSV DNA, and the reaction for each virus DNA was multiplexed with primers and probe specific for the human β-globin gene to assess specimen adequacy. Discrimination of all VZV-WT strains, including Japanese isolates and the Oka parent strain, from VZV-Oka was based upon a single nucleotide polymorphism at position 106262 in ORF 62, resulting in preferential amplification by the homologous primer pair. The assay was highly sensitive and specific for the target virus DNA, and no cross-reactions were detected with any other infectious agent. With the PCR assay as the gold standard, the sensitivity of virus culture was 53% for VZV and 77% for HSV. There was 92% agreement between the clinical diagnosis of HZ by the Clinical Evaluation Committee and the PCR assay results. PMID:19475609

Chronic verrucous varicella-zoster virus infection in patients with the acquired immunodeficiency syndrome (AIDS). Histologic and molecular biologic findings.

PubMed

LeBoit, P E; Límová, M; Yen, T S; Palefsky, J M; White, C R; Berger, T G

1992-02-01

Verrucous skin lesions have been attributed to various herpes viruses in immunosuppressed patients, including those with human immunodeficiency virus infection (HIV). We examined such lesions from six HIV-infected patients to determine the range of microscopic findings present and to establish which herpesviruses were present. Verrucous epidermal hyperplasia, pseudocarcinomatous hyperplasia, and massive hyperkeratosis correlate with the warty clinical appearance of the lesions. Herpetic cytopathic changes, including multinucleated epidermal giant cells, steel-gray nuclei, necrotic acantholytic keratinocytes, and Cowdry type A nuclear inclusions were seen most prominently in the dells between papillations and in adnexal epithelium. In two cases, increased numbers of spindled cells were seen in the dermis. Immunoperoxidase staining with anti-type IV collagen antibodies demonstrated that these findings were not those of Kaposi's sarcoma, but represent a fibrotic reaction to the infection. Viral cultures of four of the cases demonstrated the presence of varicella-zoster virus, whose presence was detected by the polymerase chain reaction in paraffin-embedded lesional tissue from all six cases. Polymerase chain reaction did not show the presence of cytomegalovirus, herpes simplex, Epstein-Barr, or human papillomavirus. We conclude that these unusual verrucous lesions are a chronic manifestation of herpes zoster infection and that the reported presence of other agents in such lesions is probably coincidental.

[Vaccines against varicella-zoster virus (VZV)].

PubMed

Salleras, Luis; Salleras, Montserrat; Soldevila, Nuria; Prat, Andreu; Garrido, Patricio; Domínguez, Ángela

2015-01-01

In Western countries, two attenuated varicella vaccines derived from the OKA strain are licensed: Varilrix® GlaxoSmithKline (OKA/RIT strain) and Varivax® Merck Sharp and Dohme (OKA/Merck strain). Currently, in Spain, varicella vaccination is only included in the Ministry of Health, Social Services and Equality official vaccination calendar for administration in adolescents who have not had the disease. Given the good results obtained in Navarra and Madrid with universal administration of the vaccine in children, it would be desirable to include the vaccine in the routine immunization schedule, with the administration of two doses at 15-18 months of age in the future. The protective efficacy of the attenuated herpes zoster vaccine was evaluated in the Shingles Prevention Study, which showed that in the short term (0-4 years) the vaccine reduced the incidence of herpes zoster by 53%, post-herpetic neuralgia by 66%, and the disease burden in immunocompetent persons aged ≥60 years by 61%. Another study demonstrated protective efficacy in persons aged 50-59 years. Over time, the protective efficacy decreases, but remains at acceptable levels, especially for post-herpetic neuralgia and the disease burden. Recently, the results of a controlled clinical trial (phase III) conducted in 18 countries to assess the protective efficacy of the inactivated subunit vaccine (glycoprotein E) adjuvanted with the adjuvant AS01B were published. The study inferred that the vaccine significantly reduced the incidence of herpes zoster in the short term (3.2 years) in people aged ≥50 years. Vaccine protection did not decrease with age at vaccination, ranging between 96.8% and 97.9% in all age groups. Copyright © 2015. Published by Elsevier España, S.L.U.

Interactome INSIDER: a structural interactome browser for genomic studies.

PubMed

Meyer, Michael J; Beltrán, Juan Felipe; Liang, Siqi; Fragoza, Robert; Rumack, Aaron; Liang, Jin; Wei, Xiaomu; Yu, Haiyuan

2018-01-01

We present Interactome INSIDER, a tool to link genomic variant information with structural protein-protein interactomes. Underlying this tool is the application of machine learning to predict protein interaction interfaces for 185,957 protein interactions with previously unresolved interfaces in human and seven model organisms, including the entire experimentally determined human binary interactome. Predicted interfaces exhibit functional properties similar to those of known interfaces, including enrichment for disease mutations and recurrent cancer mutations. Through 2,164 de novo mutagenesis experiments, we show that mutations of predicted and known interface residues disrupt interactions at a similar rate and much more frequently than mutations outside of predicted interfaces. To spur functional genomic studies, Interactome INSIDER (http://interactomeinsider.yulab.org) enables users to identify whether variants or disease mutations are enriched in known and predicted interaction interfaces at various resolutions. Users may explore known population variants, disease mutations, and somatic cancer mutations, or they may upload their own set of mutations for this purpose.

Proteome-scale human interactomics

PubMed Central

Luck, Katja; Sheynkman, Gloria M.; Zhang, Ivy; Vidal, Marc

2017-01-01

Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome-scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life. PMID:28284537

Proteome-Scale Human Interactomics.

PubMed

Luck, Katja; Sheynkman, Gloria M; Zhang, Ivy; Vidal, Marc

2017-05-01

Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life. Copyright © 2017 Elsevier Ltd. All rights reserved.

Varicella zoster vaccines and their implications for development of HSV vaccines.

PubMed

Gershon, Anne A

2013-01-05

Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinct pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV. Copyright © 2012 Elsevier Inc. All rights reserved.

Varicella zoster vaccines and their implications for development of HSV vaccines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gershon, Anne A., E-mail: aag1@columbia.edu

Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinctmore » pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV.« less

Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host-cell protein function.

PubMed

García-Dorival, Isabel; Wu, Weining; Dowall, Stuart; Armstrong, Stuart; Touzelet, Olivier; Wastling, Jonathan; Barr, John N; Matthews, David; Carroll, Miles; Hewson, Roger; Hiscox, Julian A

2014-11-07

Viral pathogenesis in the infected cell is a balance between antiviral responses and subversion of host-cell processes. Many viral proteins specifically interact with host-cell proteins to promote virus biology. Understanding these interactions can lead to knowledge gains about infection and provide potential targets for antiviral therapy. One such virus is Ebola, which has profound consequences for human health and causes viral hemorrhagic fever where case fatality rates can approach 90%. The Ebola virus VP24 protein plays a critical role in the evasion of the host immune response and is likely to interact with multiple cellular proteins. To map these interactions and better understand the potential functions of VP24, label-free quantitative proteomics was used to identify cellular proteins that had a high probability of forming the VP24 cellular interactome. Several known interactions were confirmed, thus placing confidence in the technique, but new interactions were also discovered including one with ATP1A1, which is involved in osmoregulation and cell signaling. Disrupting the activity of ATP1A1 in Ebola-virus-infected cells with a small molecule inhibitor resulted in a decrease in progeny virus, thus illustrating how quantitative proteomics can be used to identify potential therapeutic targets.

Detection of varicella-zoster virus antigens in lesional skin of zosteriform lichen planus but not in that of linear lichen planus.

PubMed

Mizukawa, Y; Horie, C; Yamazaki, Y; Shiohara, T

2012-01-01

Distinctions between 'linear lichen planus' (LP) and 'zosteriform LP' are difficult to determine solely based on clinical findings. The aim of this study is to determine whether the presence of the varicella-zoster virus (VZV) antigens could be used to differentiate the zosteriform LP from the linear LP. We immunohistochemically investigated the presence of in vivo localization of VZV antigens in 8 LP lesions (zosteriform LP: n = 5, linear LP: n = 3). We describe 2 cases of zosteriform LP without apparent prior episodes of herpes zoster, in whom VZV antigens were detected in the eccrine epithelium. Further analysis showed that VZV antigens were exclusively detected in the eccrine epithelium in the zosteriform LP lesions, but not in the linear LP lesions. Etiological differences exist between zosteriform LP and linear LP. The presence of VZV antigens in lesional skin of the former indicates a possible triggering role of this virus in the pathogenesis of this variant. Copyright © 2012 S. Karger AG, Basel.

Family history of zoster and risk of developing herpes zoster.

PubMed

Tseng, Hung Fu; Chi, Margaret; Hung, Peggy; Harpaz, Rafael; Schmid, D Scott; LaRussa, Philip; Sy, Lina S; Luo, Yi; Holmquist, Kimberly; Takhar, Harpreet; Jacobsen, Steven J

2018-01-01

Studies have investigated a possible association between family history of HZ and the occurrence of HZ. However, the results were inconclusive and susceptible to bias. We evaluated this association in an elderly population. The matched case-control study conducted at Kaiser Permanente Southern California in 2012-2015 included 656 incident HZ patients ≥60 whose skin lesion tested positive for varicella zoster virus by polymerase chain reaction. Half of the HZ patients were vaccinated with zoster vaccine as achieved by stratified sampling. The controls were randomly selected and 1:1 matched to the cases on sex, age (±1year), and zoster vaccination (±3 months of the case's vaccination date). Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Having any blood relative with a history of HZ was associated with a slightly increased risk of HZ (adjusted OR=1.37, 95% CI 1.05-1.79). The adjusted OR associated with having one and two categories of first-degree blood relatives with a history of HZ was 1.30 (95% CI: 0.97-1.73) and 2.53 (95% CI: 1.17-5.44), respectively. Our results suggested a weak association between the development of HZ and a positive family history of HZ among the elderly population. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Differentiation of strains of varicella-zoster virus by changes in neutral lipid metabolism in infected cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jerkofsky, M.; De Siervo, A.J.

1986-03-01

Eleven isolates of varicella-zoster virus were tested for their effects on the incorporation of (/sup 14/C)acetate into lipids in infected human embryonic lung cells. By relative percent, all virus isolates demonstrated a shift from polar lipid synthesis to neutral lipid, especially triglyceride, synthesis. By data expressed as counts per minute per microgram of protein, the VZV strains could be separated into two groups: those strains which depressed lipid synthesis and those strains which did not depress, and may even have stimulated, lipid, especially triglyceride, synthesis. These results may be useful in understanding the development of lipid changes seen in childrenmore » affected with Reye's syndrome following chickenpox.« less

Herpes zoster: Risk and prevention during immunomodulating therapy.

PubMed

Tran, Cong Tri; Ducancelle, Alexandra; Masson, Charles; Lunel-Fabiani, Françoise

2017-01-01

Herpes zoster can be serious or incapacitating, particularly in patients whose immune system is compromised by a disease or treatment. Immunomodulating drugs can increase the risk of infection. Well-established risk factors include advanced age and glucocorticoid therapy. The data are somewhat conflicting for medications such as methotrexate, tofacitinib, TNFα antagonists (infliximab, adalimumab, etanercept, certolizumab, and golimumab), abatacept, tocilizumab, and rituximab. Nevertheless, the risk of herpes zoster is increased in patients taking biological agents, because of the underlying diseases and/or effects of the drugs. A live attenuated herpes zoster vaccine has been proven effective and safe in immunocompetent individuals. At present, however, it is not recommended for patients with immunodeficiencies, including those taking biological drugs, as no studies have assessed its risk/benefit ratio in this population. This situation may change in the near future, as recent data support the effectiveness and safety of the herpes zoster vaccine in patients who take biotherapies or have other causes of immunodeficiency. Alternative approaches designed to protect these patients from herpes zoster and its complications are also under evaluation. There is a need to define the indications of the herpes zoster vaccine in terms of the target population, timing, modalities, and frequency, according to the underlying chronic systemic disease, age group, varicella-zoster virus status, and exposure to therapeutic agents. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells

PubMed Central

Carpenter, John E.; Grose, Charles

2014-01-01

Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as varicella or chicken pox. The virus then establishes latency in the nervous system and re-emerges, typically decades later, as zoster or shingles. We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. We found that VZV differentially induces the UPR when compared to tunicamycin treatment. For example, tunicamycin treatment moderately increased (8-fold) roughly half of the array elements while downregulating only three (one ERAD and two FOLD components). VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. PMID:25071735

The Shozu Herpes Zoster (SHEZ) study: rationale, design, and description of a prospective cohort study.

PubMed

Takao, Yukiko; Miyazaki, Yoshiyuki; Onishi, Fumitake; Kumihashi, Hideaki; Gomi, Yasuyuki; Ishikawa, Toyokazu; Okuno, Yoshinobu; Mori, Yasuko; Asada, Hideo; Yamanishi, Koichi; Iso, Hiroyasu

2012-01-01

The incidence and risk factors for herpes zoster have been studied in cross-sectional and cohort studies, although most such studies have been conducted in Western countries. Evidence from Asian populations is limited, and no cohort study has been conducted in Asia. We are conducting a 3-year prospective cohort study in Shozu County in Kagawa Prefecture, Japan to determine the incidence and predictive and immunologic factors for herpes zoster among Japanese. The participants are followed for 3 years, and a telephone survey is conducted every 4 weeks. The participants were assigned to 1 of 3 studies. Participants in study A gave information on past history of herpes zoster and completed health questionnaires. Study B participants additionally underwent varicella-zoster virus (VZV) skin testing, and study C participants additionally underwent blood testing. If the participants develop herpes zoster, we evaluate clinical symptoms, measure cell-mediated immunity and humoral immunity using venous blood sampling, photograph skin areas with rash, conduct virus identification testing by polymerase chain reaction (PCR) and virus isolation from crust sampling, and evaluate postherpetic pain. We recruited 12 522 participants aged 50 years or older in Shozu County from December 2009 through November 2010. The participation rate was 65.7% of the target population. The present study is likely to provide valuable data on the incidence and predictive and immunologic factors for herpes zoster in a defined community-based population of Japanese.

The Shozu Herpes Zoster (SHEZ) Study: Rationale, Design, and Description of a Prospective Cohort Study

PubMed Central

Takao, Yukiko; Miyazaki, Yoshiyuki; Onishi, Fumitake; Kumihashi, Hideaki; Gomi, Yasuyuki; Ishikawa, Toyokazu; Okuno, Yoshinobu; Mori, Yasuko; Asada, Hideo; Yamanishi, Koichi; Iso, Hiroyasu

2012-01-01

Background The incidence and risk factors for herpes zoster have been studied in cross-sectional and cohort studies, although most such studies have been conducted in Western countries. Evidence from Asian populations is limited, and no cohort study has been conducted in Asia. We are conducting a 3-year prospective cohort study in Shozu County in Kagawa Prefecture, Japan to determine the incidence and predictive and immunologic factors for herpes zoster among Japanese. Methods The participants are followed for 3 years, and a telephone survey is conducted every 4 weeks. The participants were assigned to 1 of 3 studies. Participants in study A gave information on past history of herpes zoster and completed health questionnaires. Study B participants additionally underwent varicella-zoster virus (VZV) skin testing, and study C participants additionally underwent blood testing. If the participants develop herpes zoster, we evaluate clinical symptoms, measure cell-mediated immunity and humoral immunity using venous blood sampling, photograph skin areas with rash, conduct virus identification testing by polymerase chain reaction (PCR) and virus isolation from crust sampling, and evaluate postherpetic pain. Results We recruited 12 522 participants aged 50 years or older in Shozu County from December 2009 through November 2010. The participation rate was 65.7% of the target population. Conclusions The present study is likely to provide valuable data on the incidence and predictive and immunologic factors for herpes zoster in a defined community-based population of Japanese. PMID:22343323

Penile herpes zoster: an unusual location for a common disease.

PubMed

Bjekic, Milan; Markovic, Milica; Sipetic, Sandra

2011-01-01

Herpes zoster is a common dermatological condition which affects up to 20% of the population, most frequently involving the thoracic and facial dermatomes with sacral lesions occurring rarely and only a few reported cases of penile shingles. We report two cases of unusual penile clinical presentations of varicella zoster virus infection in immunocompetent men. The patients presented with grouped clusters of vesicles and erythema on the left side of penile shaft and posterior aspect of the left thigh and buttock, involving s2-s4 dermatomes. The lesions resolved quickly upon administration of oral antiviral therapy. Penile herpes zoster should not be overlooked in patients with unilateral vesicular rash.

Urinary retention, erectile dysfunction and meningitis due to sacral herpes zoster: a case report and review of the literature.

PubMed

Erol, B; Avci, A; Eken, C; Ozgok, Y

2009-01-01

Zona zoster infection is often associated with painful erythematous vesicular eruptions of the skin or mucous membranes. Varicella zoster virus which stays latent in the sensorial root ganglia causes zona zoster infection. The most recognized feature of zona zoster is the dermatomal distribution of vesicular rashes. In the present case report, we state an unusual presentation of sacral zona zoster with urinary retention, erectile dysfunction and meningitis. Copyright 2009 S. Karger AG, Basel.

Productive vs non-productive infection by cell-free Varicella zoster virus of human neurons derived from embryonic stem cells is dependent upon infectious viral dose

PubMed Central

Sloutskin, Anna; Kinchington, Paul R.; Goldstein, Ronald S.

2013-01-01

Varicella Zoster virus (VZV) productively infects humans causing varicella upon primary infection and herpes zoster upon reactivation from latency in neurons. In-vitro studies using cell-associated VZV infection have demonstrated productive VZV-infection, while a few recent studies of human neurons derived from stem cells incubated with cell-free, vaccine-derived VZV did not result in generation of infectious virus. In the present study, 90%-pure human embryonic stem cell-derived neurons were incubated with recombinant cell-free pOka-derived made with an improved method or with VZV vaccine. We found that cell-free pOka and vOka at higher multiplicities of infection elicited productive infection in neurons followed by spread of infection, cytopathic effect and release of infectious virus into the medium. These results further validate the use of this unlimited source of human neurons for studying unexplored aspects of VZV interaction with neurons such as entry, latency and reactivation. PMID:23769240

Immunohistochemical identification of varicella-zoster virus gene 63-encoded protein (IE63) and late (gE) protein on smears and cutaneous biopsies: implications for diagnostic use.

PubMed

Nikkels, A F; Debrus, S; Sadzot-Delvaux, C; Piette, J; Rentier, B; Piérard, G E

1995-12-01

Early and specific recognition of varicella zoster virus (VZV) infection is of vital concern in immunocompromised patients. The aim of this study was to compare the diagnostic accuracy of histochemical and immunohistochemical identification of the VZV ORF63 encoded protein (IE63) and of the VZV late protein gE on smears and formalin-fixed paraffin-embedded skin sections taken from lesions clinically diagnosed as varicella (n = 15) and herpes zoster (n = 51). Microscopic examinations of Tzanck smears and skin sections yielded a diagnostic accuracy of Herpesviridae infections in 66.7% (10/15) and 92.3% (12/13) of varicella, and 74.4% (29/39) and 87.8% (43/49) of herpes zoster, respectively. Immunohistochemistry applied to varicella provided a type-specific virus diagnostic accuracy of 86.7% (13/15; IE63) and 100% (15/15; gE) on smears, and of 92.3% for both VZV proteins on skin sections. In herpes zoster, the diagnostic accuracy of immunohistochemistry reached 92.3% (36/39; IE63) and 94.9% (37/39; gE) on smears, and 91.7% (44/48; IE63) and 91.8% (45/49; gE) on skin sections. These findings indicate that the immunohistochemical detection of IE63 and gE on both smears and skin sections yields a higher specificity and sensitivity than standard microscopic assessments.

Altered phenotype and functionality of varicella zoster virus-specific cellular immunity in individuals with active infection.

PubMed

Schub, David; Janssen, Eva; Leyking, Sarah; Sester, Urban; Assmann, Gunter; Hennes, Pia; Smola, Sigrun; Vogt, Thomas; Rohrer, Tilman; Sester, Martina; Schmidt, Tina

2015-02-15

Varicella zoster virus (VZV) establishes lifelong persistence and may reactivate in individuals with impaired immune function. To investigate immunologic correlates of protection and VZV reactivation, we characterized specific immunity in 207 nonsymptomatic immunocompetent and 132 immunocompromised individuals in comparison with patients with acute herpes zoster. VZV-specific CD4 T cells were quantified flow cytometrically after stimulation and characterized for expression of interferon-γ, interleukin 2, and tumor necrosis factor α and surface markers for differentiation (CD127) and anergy (cytotoxic T lymphocyte antigen 4 [CTLA-4] and programmed death [PD]-1). Immunoglobulin G and A levels were quantified using an enzyme-linked immunosorbent assay. In healthy individuals, VZV-specific antibody and T-cell levels were age dependent, with the highest median VZV-specific CD4 T-cell frequencies of 0.108% (interquartile range, 0.121%) during adolescence. VZV-specific T-cell profiles were multifunctional with predominant expression of all 3 cytokines, CD127 positivity, and low expression of CTLA-4 and PD-1. Nonsymptomatic immunocompromised patients had similar VZV-specific immunologic properties except for lower T-cell frequencies (P<.001) and restricted cytokine expression. In contrast, significantly elevated antibody- and VZV-specific CD4 T-cell levels were found in patients with zoster. Their specific T cells showed a shift in cytokine expression toward interferon γ single positivity, an increase in CTLA-4 and PD-1, and a decrease in CD127 expression (all P<.001). This phenotype normalized after resolution of symptoms. VZV-specific CD4-T cells in patients with zoster bear typical features of anergy. This phenotype is reversible and may serve as adjunct tool for monitoring VZV reactivations in high-risk patients. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions

Rapid Detection of the Varicella Zoster Virus

NASA Technical Reports Server (NTRS)

Lewis, Michelle P.; Harding, Robert

2011-01-01

1.Technology Description-Researchers discovered that when the Varicella Zoster Virus (VZV) reactivates from latency in the body, the virus is consistently present in saliva before the appearance of skin lesions. A small saliva sample is mixed with a specialized reagent in a test kit. If the virus is present in the saliva sample, the mixture turns a red color. The sensitivity and specificity emanates from an antibody-antigen reaction. This technology is a rapid, non-invasive, point of-of-care testing kit for detecting the virus from a saliva sample. The device is easy to use and can be used in clinics and in remote locations to quickly detect VZV and begin treatment with antiviral drugs. 2.Market Opportunity- RST Bioscience will be the first and only company to market a rapid, same day test kit for the detection of VZV in saliva. The RST detection test kit will have several advantages over existing, competitive technology. The test kit is self contained and laboratory equipment is not required for analysis of the sample. Only a single saliva sample is required to be taken instead of blood or cerebral spinal fluid. The test kit is portable, sterile and disposable after use. RST detection test kits require no electrical power or expensive storage equipment and can be used in remote locations. 3.Market Analysis- According to the CDC, it is estimated that 1 million cases of shingles occur each year in the U.S. with more than half over the age of sixty. There is a high demand for rapid diagnostics by the public. The point-of-care testing (POCT) market is growing faster than other segments of in vitro diagnostics. According to a July 2007 InteLab Corporation industry report the overall market for POCT was forecast to increase from $10.3 billion in 2005 to $18.7 billion by 2011. The market value of this test kit has not been determined. 4.Competition- The VZV vaccine prevents 50% of cases and reduces neuralgia by 66%. The most popular test detects VZV-specific IgM antibody

Vaccination against herpes zoster in developed countries

PubMed Central

Drolet, Mélanie; Oxman, Michael N.; Levin, Myron J.; Schmader, Kenneth E.; Johnson, Robert W.; Patrick, David; Mansi, James A.; Brisson, Marc

2013-01-01

Although progress has been made in the treatment of herpes zoster (HZ) and postherpetic neuralgia (PHN), available therapeutic options are only partially effective. Given evidence that a live-attenuated varicella-zoster-virus vaccine is effective at reducing the incidence of HZ, PHN and the burden of illness, policymakers and clinicians are being asked to make recommendations regarding the use of the zoster vaccine. In this report, we summarize the evidence regarding the: (1) burden of illness; (2) vaccine efficacy and safety; and (3) cost-effectiveness of vaccination, to assist evidence-based policy making and guide clinicians in their recommendations. First, there is general agreement that the overall burden of illness associated with HZ and PHN is substantial. Second, the safety and efficacy of the zoster vaccine at reducing the burden of illness due to HZ and the incidence of PHN have been clearly demonstrated in large placebo-controlled trials. However, uncertainty remains about the vaccine’s duration of protection. Third, vaccination against HZ is likely to be cost-effective when the vaccine is given at approximately 65 y of age, if vaccine duration is longer than 10 y. PMID:23324598

Varicella zoster virus in the temporal artery of a patient with giant cell arteritis.

PubMed

Nagel, Maria A; Khmeleva, Nelly; Boyer, Philip J; Choe, Alexander; Bert, Robert; Gilden, Don

2013-12-15

We recently detected varicella zoster virus (VZV) in the temporal arteries (TA) of 5/24 patients with clinically suspect giant cell arteritis (GCA) whose TAs were GCA-negative pathologically; in those GCA-negative, VZV+TAs, virus antigen predominated in the arterial adventitia, but without medial necrosis and multinucleated giant cells. During our continuing search for VZV antigen in GCA-negative TAs, in the TA of one subject, we found abundant VZV antigen, as well as VZV DNA, in multiple regions (skip areas) of the TA spanning 350 μm, as well as in skeletal muscle adjacent to the infected TA. Additional pathological analysis of sections adjacent to those containing viral antigen revealed inflammation involving the arterial media and abundant multinucleated giant cells characteristic of GCA. Detection of VZV in areas of the TA with pathological features of GCA warrants further correlative pathological-virological analysis of VZV in GCA. © 2013.

Herpes zoster involving penis and scrotum: an unusual occurrence.

PubMed

Arshad, Abdul Rehman; Alvi, Kamran Yousaf; Chaudhary, Ammad Akram

2015-03-01

Herpes zoster is an infectious vesicular skin rash in a dermatomal distribution caused by Varicella zoster virus. It occurs very uncommonly in sacral dermatomes. We describe a case with rash on penis and scrotum due to involvement of S2 dermatome in a young male. The disease followed an uneventful course and the patient recovered completely without any sequelae or complications. This case is being presented to highlight its unusual location and to discuss differentiation from another viral infection commonly seen at this site.

Rare presentation of acute urinary retention secondary to herpes zoster.

PubMed

Ginsberg, P C; Harkaway, R C; Elisco, A J; Rosenthal, B D

1998-09-01

There are many causes of acute urinary retention. Reported here is a case of one of the more rare causes: herpes zoster. Fewer than 70 cases have been reported in the literature since 1890. In the present clinical environment where many patients are immunocompromised, reports of herpes zoster and its sequelae are no longer thought of as anecdotal. The virus may interrupt the detrusor reflex due to involvement of the sacral dorsal root ganglia. Urinary retention with sensory loss of both bladder and rectum as well as flaccid paralysis of the detrusor can develop in patients with herpes zoster. Fortunately, the outcome of this process is benign and full recovery of the detrusor is likely.

[Herpes zoster of the trigeminal nerve: a case report and review of the literature].

PubMed

Carbone, V; Leonardi, A; Pavese, M; Raviola, E; Giordano, M

2004-01-01

Herpes zoster (shingles) is caused when the varicella zoster virus that has remained latent since an earlier varicella infection (chicken-pox) is reactivated. Herpes Zoster is a less common and endemic disease than varicella: factors causing reactivation are still not well known, but it occurs in older and/or immunocompromised individuals. Following reactivation, centrifugal migration of herpes zoster virus (HZV) occurs along sensory nerves to produce a characteristic painful cutaneous or mucocutaneous vesicular eruption that is generally limited to the single affected dermatome. Herpes zoster may affect any sensory ganglia and its cutaneous nerve: the most common sites affected are thoracic dermatomes (56%), followed by cranial nerves (13%) and lumbar (13%), cervical (11%) and sacral nerves (4%). Among cranial nerves, the trigeminal and facial nerves are the most affected due to reactivation of HZV latent in gasserian and geniculated ganglia. The 1st division of the trigeminal nerve is commonly affected, whereas the 2nd and the 3rd are rarely involved. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist, since many diseases can cause orofacial pain, and the diagnosis must be established before final treatment. A literature review of herpes zoster of the trigeminal nerve is presented and the clinical presentation, differential diagnosis and treatment modalities are underlined. A case report is presented.

Varicella-Zoster Virus Proteins in Skin Lesions: Implications for a Novel Role of ORF29p in Chickenpox

PubMed Central

Annunziato, Paula W.; Lungu, Octavian; Panagiotidis, Christos; Zhang, Jing H.; Silvers, David N.; Gershon, Anne A.; Silverstein, Saul J.

2000-01-01

Skin biopsy samples from varicella-zoster virus (VZV)-infected patients examined by immunohistochemistry demonstrated VZV replication in nonepithelial cell types. ORF29p, a nonstructural nuclear protein, was found in nerves of two of six patients with chickenpox. In tissue culture, ORF29p was secreted by VZV-infected fibroblasts. Extracellular ORF29p can be taken up through endocytosis by human neurons, implying a novel role for this protein in pathogenesis. PMID:10644373

Herpes zoster of gingiva in an older woman: a rare case report.

PubMed

Chopra, Aditi; Sivaraman, Karthik; Thomas, Betsy S

2017-06-01

The aim of the article is to highlight the distinguishing features of secondary varicella gingival infection in an older women. Herpes zoster is an acute sporadic, painful viral infection in older people caused by the reactivation of the latent varicella zoster virus. Herpes zoster affecting the gingiva without any dermal lesions is a rare pathological condition that mimics many intraoral vesiculobullous lesions. The ambiguous nature of this condition creates a diagnostic dilemma. A 58-year-old woman presented with an acute, unilateral and persistent burning sensation and pain in the gingiva with desqaumating vesicullobulous lesion. The women was diagnosed with secondary varicella zoster infection. Herpes zoster of the gingiva could manifest as painful desquamative vesicular lesions, pulpal or other painful neuralgic condition in older individuals which need careful diagnosis before formulating appropiate treatment plan. © 2016 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Herpes zoster ophthalmicus.

PubMed

Sanjay, Srinivasan; Huang, Philemon; Lavanya, Raghavan

2011-02-01

complete. Vasculitis within the orbital apex (orbital apex syndrome) or brainstem dysfunction is postulated to be the cause of cranial nerve palsies. A vaccine of a lyophilized preparation of the oka strain of live, attenuated varicella-zoster virus is suggested for patients who are at risk of developing HZ and has been shown to boost immunity against HZ virus in older patients.

A pseudoreceptor modelling study of the varicella-zoster virus and human thymidine kinase binding sites

NASA Astrophysics Data System (ADS)

Greenidge, Paulette A.; Merz, Alfred; Folkers, Gerd

1995-12-01

A representative range of pyrimidine nucleoside analogues that are known to inhibit herpes simplex virus (HSV) replication have been used to construct receptor binding site models for the varicella-zoster virus (VZV), thymidine kinase (TK) and human TK1. Given a set of interacting ligands, superimposed in such a manner as to define a pharmacophore, the pseudoreceptor modelling technique Yak provides a means of building binding site models of macromolecules for which no three-dimensional experimental structures are available. Once the models have been evaluated by their ability to reproduce experimental binding data [Vedani et al., J. Am. Chem. Soc., 117 (1995) 4987], they can be used for predictive purposes. Calculated and experimental values of relative binding affinity are compared. Our models suggest that the substitution of one residue may be sufficient to determine ligand subtype affinity.

Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age.

PubMed

Chlibek, Roman; Bayas, José M; Collins, Harry; de la Pinta, Maria Luisa Rodriguez; Ledent, Edouard; Mols, Johann F; Heineman, Thomas C

2013-12-15

An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses. This was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were randomized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline. Following each dose, solicited events were recorded for 7 days and unsolicited adverse events for 30 days. Serious adverse events were collected for 1 year. Cell-mediated and humoral immune responses were assessed at baseline and following each dose. No vaccine-related severe adverse events were reported. Solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom. Immune responses were significantly enhanced by AS01B and AS01E compared to unadjuvanted gE and were significantly stronger for gE/AS01B than for gE/AS01E. AS01 improved the immunogenicity of gE while retaining acceptable safety and reactogenicity profiles. The enhancement of gE-specific cellular and humoral responses was adjuvant dose dependent. NCT00802464.

Altered cellular and humoral immunity to varicella-zoster virus in patients with autoimmune diseases.

PubMed

Rondaan, Christien; de Haan, Aalzen; Horst, Gerda; Hempel, J Cordelia; van Leer, Coretta; Bos, Nicolaas A; van Assen, Sander; Bijl, Marc; Westra, Johanna

2014-11-01

Patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (Wegener's) (GPA) have a 3-20-fold increased risk of herpes zoster compared to the general population. The aim of this study was to evaluate if susceptibility is due to decreased levels of cellular and/or humoral immunity to the varicella-zoster virus (VZV). A cross-sectional study of VZV-specific immunity was performed in 38 SLE patients, 33 GPA patients, and 51 healthy controls. Levels of IgG and IgM antibodies to VZV were measured using an in-house glycoprotein enzyme-linked immunosorbent assay (ELISA). Cellular responses to VZV were determined by interferon-γ (IFNγ) enzyme-linked immunospot (ELISpot) assay and carboxyfluorescein succinimidyl ester (CFSE) dye dilution proliferation assay. Levels of IgG antibodies to VZV were increased in SLE patients as compared to healthy controls, but levels of IgM antibodies to VZV were not. Antibody levels in GPA patients did not differ significantly from levels in healthy controls. In response to stimulation with VZV, decreased numbers of IFNγ spot-forming cells were found among SLE patients (although not GPA patients) as compared to healthy controls. Proliferation of CD4+ T cells in response to stimulation with VZV was decreased in SLE patients but not GPA patients. SLE patients have increased levels of IgG antibodies against VZV, while cellular immunity is decreased. In GPA patients, antibody levels as well as cellular responses to VZV were comparable to those in healthy controls. These data suggest that increased prevalence of herpes zoster in SLE patients is due to a poor cellular response. Vaccination strategies should aim to boost cellular immunity against VZV. Copyright © 2014 by the American College of Rheumatology.

Varicella Zoster Virus–Specific Immune Responses to a Herpes Zoster Vaccine in Elderly Recipients With Major Depression and the Impact of Antidepressant Medications

PubMed Central

Irwin, Michael R.; Levin, Myron J.; Laudenslager, Mark L.; Olmstead, Richard; Lucko, Anne; Lang, Nancy; Carrillo, Carmen; Stanley, Harold A.; Caulfield, Michael J.; Weinberg, Adriana; Chan, Ivan S. F.; Clair, Jim; Smith, Jeff G.; Marchese, R. D.; Williams, Heather M.; Beck, Danielle J.; McCook, Patricia T.; Zhang, Jane H.; Johnson, Gary; Oxman, Michael N.

2013-01-01

Background. The Depression Substudy of the Shingles Prevention Study (SPS) was designed to evaluate the association between major depression and immune responses to a high-titer live attenuated varicella zoster virus (VZV) vaccine (zoster vaccine), which boosts cell-mediated immunity (CMI) to VZV and decreases the incidence and severity of herpes zoster (HZ). The Depression Substudy was a 2-year longitudinal cohort study in 92 community-dwelling adults ≥60 years of age who were enrolled in the SPS, a large, double-blind, placebo-controlled Veterans Affairs Cooperative zoster vaccine efficacy study. Methods. Forty subjects with major depressive disorder, stratified by use of antidepressant medications, and 52 age- and sex-matched controls with no history of depression or other mental illness had their VZV-CMI measured prior to vaccination with zoster vaccine or placebo and at 6 weeks, 1 year, and 2 years postvaccination. Results. Depressed subjects who were not treated with antidepressant medications had lower levels of VZV-CMI following administration of zoster vaccine than nondepressed controls or depressed subjects receiving antidepressants even when antidepressant medications failed to alter depressive symptom severity (P < .005). Similar results were obtained taking into account the time-varying status of depression and use of antidepressant medications, as well as changes in depressive symptoms, during the postvaccination period. Conclusions. Depressed patients have diminished VZV-CMI responses to zoster vaccine, and treatment with antidepressant medication is associated with normalization of these responses. Because higher levels of VZV-CMI correlate with lower risk and severity of HZ, untreated depression may increase the risk and severity of HZ and reduce the efficacy of zoster vaccine. PMID:23413415

Host cell interactome of PA protein of H5N1 influenza A virus in chicken cells.

PubMed

Wang, Qiao; Li, Qinghe; Liu, Ranran; Zheng, Maiqing; Wen, Jie; Zhao, Guiping

2016-03-16

Influenza A virus (IAV) heavily depends on viral-host protein interactions in order to replicate and spread. Identification of host factors that interact with viral proteins plays crucial roles in understanding the mechanism of IAV infection. Here we report the interaction landscape of H5N1 IAV PA protein in chicken cells through the use of affinity purification and mass spectrometry. PA protein was expressed in chicken cells and PA interacting complexes were captured by co-immunoprecipitation and analyzed by mass spectrometry. A total of 134 proteins were identified as PA-host interacting factors. Protein complexes including the minichromosome maintenance complex (MCM), 26S proteasome and the coat protein I (COPI) complex associated with PA in chicken cells, indicating the essential roles of these functional protein complexes during the course of IAV infection. Gene Ontology and pathway enrichment analysis both showed strong enrichment of PA interacting proteins in the category of DNA replication, covering genes such as PCNA, MCM2, MCM3, MCM4, MCM5 and MCM7. This study has uncovered the comprehensive interactome of H5N1 IAV PA protein in its chicken host and helps to establish the foundation for further investigation into the newly identified viral-host interactions. Influenza A virus (IAV) is a great threat to public health and avian production. However, the manner in which avian IAV recruits the host cellular machinery for replication and how the host antagonizes the IAV infection was previously poorly understood. Here we present the viral-host interactome of the H5N1 IAV PA protein and reveal the comprehensive association of host factors with PA. Copyright © 2016 Elsevier B.V. All rights reserved.

Simultaneous Occurrence of Varicella Zoster Virus-Induced Pancreatitis and Hepatitis in a Renal Transplant Recipient: A Case Report and Review of Literature

PubMed Central

Chhabra, Puneet; Ranjan, Priyadarshi; Bhasin, Deepak K

2017-01-01

Introduction: Gastrointestinal complications are common after renal transplantation, including oral lesions, esophagitis, gastritis, diarrhea, and colon carcinoma. The differential diagnosis is difficult in this scenario because multiple factors such as drugs, infections, and preexisting gastrointestinal disease come into play. Case Presentation: We report a case of varicella zoster virus-induced pancreatitis and hepatitis in a renal transplant recipient. The patient underwent renal transplantation 3 years earlier and now presented with severe pain in the epigastrium radiating to his back and had raised serum lipase levels and skin lesions characteristic of varicella. Liver enzyme levels were also elevated. He was started on a regimen of acyclovir. His pain improved in 24 hours, and liver enzyme levels returned to normal in 48 hours. Discussion: There is a paucity of literature on the simultaneous occurrence of varicella zoster virus-induced hepatitis and pancreatitis in both immunocompetent and immunocompromised patients. Our case highlights the gastrointestinal complications of varicella infection in immunocompromised patients that may precede the characteristic dermatologic manifestations, and the fact that rarely both hepatitis and pancreatitis may be seen. PMID:28333601

Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection.

PubMed

Buckingham, Erin M; Carpenter, John E; Jackson, Wallen; Zerboni, Leigh; Arvin, Ann M; Grose, Charles

2015-01-06

Autophagy is a process by which misfolded and damaged proteins are sequestered into autophagosomes, before degradation in and recycling from lysosomes. We have extensively studied the role of autophagy in varicella-zoster virus (VZV) infection, and have observed that vesicular cells are filled with >100 autophagosomes that are easily detectable after immunolabeling for the LC3 protein. To confirm our hypothesis that increased autophagosome formation was not secondary to a block, we examined all conditions of VZV infection as well as carrying out two assessments of autophagic flux. We first investigated autophagy in human skin xenografts in the severe combined immunodeficiency (SCID) mouse model of VZV pathogenesis, and observed that autophagosomes were abundant in infected human skin tissues. We next investigated autophagy following infection with sonically prepared cell-free virus in cultured cells. Under these conditions, autophagy was detected in a majority of infected cells, but was much less than that seen after an infected-cell inoculum. In other words, inoculation with lower-titered cell-free virus did not reflect the level of stress to the VZV-infected cell that was seen after inoculation of human skin in the SCID mouse model or monolayers with higher-titered infected cells. Finally, we investigated VZV-induced autophagic flux by two different methods (radiolabeling proteins and a dual-colored LC3 plasmid); both showed no evidence of a block in autophagy. Overall, therefore, autophagy within a VZV-infected cell was remarkably different from autophagy within an HSV-infected cell, whose genome contains two modifiers of autophagy, ICP34.5 and US11, not present in VZV.

Susceptibility to measles, rubella, mumps, and varicella-zoster viruses among healthcare workers.

PubMed

Aypak, Cenk; Bayram, Yasemin; Eren, Hayriye; Altunsoy, Adalet; Berktaş, Mustafa

2012-01-01

It is important to identify and immunize susceptible healthcare workers to prevent and control hospital infections. Our aim was to evaluate the specific antibodies against the measles, mumps, and rubella viruses and the varicella zoster virus among healthcare workers in a tertiary-care hospital. A total of 284 healthcare workers (89 men and 195 women; mean age, 33.5 ± 11 years), including 111 nurses, 87 physicians, 34 laboratory technicians, and 52 members of the housekeeping staff, of Van Training and Research Hospital were enrolled in this study. Antibodies were detected with an enzyme-linked immunosorbent assay. The numbers of workers with serological susceptibility to mumps, measles, rubella, or chicken pox were 26 (9.2%), 18 (6.3%), 7 (2.5%), and 5 (1.8%), respectively. Although the difference was not statistical significant, the rate of seroprevalence of antibodies was lowest for measles (90.8%; p>0.05). Susceptibility to measles, mumps, and rubella, and chicken pox was more prevalent among young healthcare workers (p<0.001). Not all healthcare workers born before 1957 were immune to these vaccine-preventable diseases. These data confirm that screening and vaccination of susceptible healthcare workers is essential regardless of age.

Eye and Periocular Skin Involvement in Herpes Zoster Infection

PubMed Central

Kalogeropoulos, Chris D.; Bassukas, Ioannis D.; Moschos, Marilita M.; Tabbara, Khalid F.

2015-01-01

Herpes zoster ophthalmicus (HZO) is a clinical manifestation of the reactivation of latent varicella zoster virus (VZV) infection and is more common in people with diminished cell-mediated immunity. Lesions and pain correspond to the affected dermatomes, mostly in first or second trigeminal branch and progress from maculae, papules to vesicles and form pustules, and crusts. Complications are cutaneous, visceral, neurological, ocular, but the most debilitating is post-herpetic neuralgia. Herpes zoster ophthalmicus may affect all the ophthalmic structures, but most severe eye-threatening complications are panuveitis, acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN) as well. Antiviral medications remain the primary therapy, mainly useful in preventing ocular involvement when begun within 72 hours after the onset of the rash. Timely diagnosis and management of HZO are critical in limiting visual morbidity. Vaccine in adults over 60 was found to be highly effective to boost waning immunity what reduces both the burden of herpes zoster (HZ) disease and the incidence of post-herpetic neuralgia (PHN). PMID:27800502

Varicella zoster virus-associated morbidity and mortality in Africa: a systematic review protocol

PubMed Central

Hussey, Hannah S; Abdullahi, Leila H; Collins, Jamie E; Muloiwa, Rudzani; Hussey, Gregory D; Kagina, Benjamin M

2016-01-01

Introduction Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. Methods and analysis Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Ethics and dissemination As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated

Varicella zoster virus-associated morbidity and mortality in Africa: a systematic review protocol.

PubMed

Hussey, Hannah S; Abdullahi, Leila H; Collins, Jamie E; Muloiwa, Rudzani; Hussey, Gregory D; Kagina, Benjamin M

2016-04-20

Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals. CRD42015026144. Published by

Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.

PubMed

Grigoryan, Sergei; Yee, Michael B; Glick, Yair; Gerber, Doron; Kepten, Eldad; Garini, Yuval; Yang, In Hong; Kinchington, Paul R; Goldstein, Ronald S

2015-01-01

Varicella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon primary infection and Herpes zoster (shingles) following reactivation in latently infected neurons, is known to be fusogenic. It forms polynuclear syncytia in culture, in varicella skin lesions and in infected fetal human ganglia xenografted to mice. After axonal infection using VZV expressing green fluorescent protein (GFP) in compartmentalized microfluidic cultures there is diffuse filling of axons with GFP as well as punctate fluorescence corresponding to capsids. Use of viruses with fluorescent fusions to VZV proteins reveals that both proteins encoded by VZV genes and those of the infecting cell are transferred in bulk from infecting non-neuronal cells to axons. Similar transfer of protein to axons was observed following cell associated HSV1 infection. Fluorescence recovery after photobleaching (FRAP) experiments provide evidence that this transfer is by diffusion of proteins from the infecting cells into axons. Time-lapse movies and immunocytochemical experiments in co-cultures demonstrate that non-neuronal cells fuse with neuronal somata and proteins from both cell types are present in the syncytia formed. The fusogenic nature of VZV therefore may enable not only conventional entry of virions and capsids into axonal endings in the skin by classical entry mechanisms, but also by cytoplasmic fusion that permits viral protein transfer to neurons in bulk.

Direct Transfer of Viral and Cellular Proteins from Varicella-Zoster Virus-Infected Non-Neuronal Cells to Human Axons

PubMed Central

Grigoryan, Sergei; Yee, Michael B; Glick, Yair; Gerber, Doron; Kepten, Eldad; Garini, Yuval; Yang, In Hong; Kinchington, Paul R.; Goldstein, Ronald S.

2015-01-01

Varicella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon primary infection and Herpes zoster (shingles) following reactivation in latently infected neurons, is known to be fusogenic. It forms polynuclear syncytia in culture, in varicella skin lesions and in infected fetal human ganglia xenografted to mice. After axonal infection using VZV expressing green fluorescent protein (GFP) in compartmentalized microfluidic cultures there is diffuse filling of axons with GFP as well as punctate fluorescence corresponding to capsids. Use of viruses with fluorescent fusions to VZV proteins reveals that both proteins encoded by VZV genes and those of the infecting cell are transferred in bulk from infecting non-neuronal cells to axons. Similar transfer of protein to axons was observed following cell associated HSV1 infection. Fluorescence recovery after photobleaching (FRAP) experiments provide evidence that this transfer is by diffusion of proteins from the infecting cells into axons. Time-lapse movies and immunocytochemical experiments in co-cultures demonstrate that non-neuronal cells fuse with neuronal somata and proteins from both cell types are present in the syncytia formed. The fusogenic nature of VZV therefore may enable not only conventional entry of virions and capsids into axonal endings in the skin by classical entry mechanisms, but also by cytoplasmic fusion that permits viral protein transfer to neurons in bulk. PMID:25973990

Antibody-capture enzyme-linked immunosorbent assays that use enzyme-labelled antigen for detection of virus-specific immunoglobulin M, A and G in patients with varicella or herpes zoster.

PubMed Central

van Loon, A. M.; van der Logt, J. T.; Heessen, F. W.; Heeren, M. C.; Zoll, J.

1992-01-01

Antibody-capture enzyme-linked immunosorbent assays (AC-ELISA) which use enzyme-labelled antigen were developed for detection of varicella-zoster virus-(VZV) specific IgM, IgA and IgG antibody in patients with varicella or herpes zoster and in sera from healthy individuals. All 18 patients with varicella developed a VZV-IgM and a VZV-IgG response, 17 also a VZV-IgA response. In contrast, all 19 patients with herpes zoster were shown to be positive for VZV-IgA whereas only 13 of these reacted positively for VZV-IgM. A VZV-IgM response was detected in only two sera from 100 healthy individuals and an IgA response in only one. The presence of virus-specific IgA and IgG in the cerebrospinal fluid as determined by AC-ELISA was a useful indicator of VZV infection of the central nervous system. By AC-ELISA, VZV-IgG was detected predominantly in sera from patients with acute or recent VZV infection. Only 14 sera from 100 healthy individuals were positive for VZV-IgG by AC-ELISA, whereas all were positive by an indirect ELISA. These results indicate that AC-ELISA's may be useful assays for determination for acute or recurrent VZV infection, but are not suitable for determination of past infection with this virus. PMID:1312479

Prevention strategies for herpes zoster and post-herpetic neuralgia

PubMed Central

Levin, Myron J.; Gershon, Anne A.; Dworkin, Robert H.; Brisson, Marc; Stanberry, Lawrence

2017-01-01

SUMMARY Impairment of varicella zoster virus (VZV)-specific cell-mediated immunity, including impairment due to immunosenescence, is associated with an increased risk of developing herpes zoster (HZ), whereas levels of anti-VZV antibodies do not correlate with HZ risk. This crucial role of VZV-specific cell-mediated immunity suggests that boosting these responses by vaccination will be an effective strategy for reducing the burden of HZ. Other strategies focus on preventing the major complication of HZ – post-herpetic neuralgia. These strategies include pre-emptive treatment with drugs such as tricyclic antidepressants, anticonvulsants and analgesics. PMID:20510262

Functional Characterization of the Serine-Rich Tract of Varicella-Zoster Virus IE62.

PubMed

Kim, Seong K; Shakya, Akhalesh K; Kim, Seongman; O'Callaghan, Dennis J

2016-01-15

The immediate early 62 protein (IE62) of varicella-zoster virus (VZV), a major viral trans-activator, initiates the virus life cycle and is a key component of pathogenesis. The IE62 possesses several domains essential for trans-activation, including an acidic trans-activation domain (TAD), a serine-rich tract (SRT), and binding domains for USF, TFIIB, and TATA box binding protein (TBP). Transient-transfection assays showed that the VZV IE62 lacking the SRT trans-activated the early VZV ORF61 promoter at only 16% of the level of the full-length IE62. When the SRT of IE62 was replaced with the SRT of equine herpesvirus 1 (EHV-1) IEP, its trans-activation activity was completely restored. Herpes simplex virus 1 (HSV-1) ICP4 that lacks a TAD very weakly (1.5-fold) trans-activated the ORF61 promoter. An IE62 TAD-ICP4 chimeric protein exhibited trans-activation ability (10.2-fold), indicating that the IE62 TAD functions with the SRT of HSV-1 ICP4 to trans-activate viral promoters. When the serine and acidic residues of the SRT were replaced with Ala, Leu, and Gly, trans-activation activities of the modified IE62 proteins IE62-SRTΔSe and IE62-SRTΔAc were reduced to 46% and 29% of wild-type activity, respectively. Bimolecular complementation assays showed that the TAD of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with Mediator 25 in human melanoma MeWo cells. The SRT of IE62 interacted with the nucleolar-ribosomal protein EAP, which resulted in the formation of globular structures within the nucleus. These results suggest that the SRT plays an important role in VZV viral gene expression and replication. The immediate early 62 protein (IE62) of varicella-zoster virus (VZV) is a major viral trans-activator and is essential for viral growth. Our data show that the serine-rich tract (SRT) of VZV IE62, which is well conserved within the alphaherpesviruses, is needed for trans-activation mediated by the acidic trans-activation domain (TAD). The TADs of IE62, EHV-1 IEP, and HSV

Functional Characterization of the Serine-Rich Tract of Varicella-Zoster Virus IE62

PubMed Central

Shakya, Akhalesh K.; Kim, Seongman; O'Callaghan, Dennis J.

2015-01-01

ABSTRACT The immediate early 62 protein (IE62) of varicella-zoster virus (VZV), a major viral trans-activator, initiates the virus life cycle and is a key component of pathogenesis. The IE62 possesses several domains essential for trans-activation, including an acidic trans-activation domain (TAD), a serine-rich tract (SRT), and binding domains for USF, TFIIB, and TATA box binding protein (TBP). Transient-transfection assays showed that the VZV IE62 lacking the SRT trans-activated the early VZV ORF61 promoter at only 16% of the level of the full-length IE62. When the SRT of IE62 was replaced with the SRT of equine herpesvirus 1 (EHV-1) IEP, its trans-activation activity was completely restored. Herpes simplex virus 1 (HSV-1) ICP4 that lacks a TAD very weakly (1.5-fold) trans-activated the ORF61 promoter. An IE62 TAD-ICP4 chimeric protein exhibited trans-activation ability (10.2-fold), indicating that the IE62 TAD functions with the SRT of HSV-1 ICP4 to trans-activate viral promoters. When the serine and acidic residues of the SRT were replaced with Ala, Leu, and Gly, trans-activation activities of the modified IE62 proteins IE62-SRTΔSe and IE62-SRTΔAc were reduced to 46% and 29% of wild-type activity, respectively. Bimolecular complementation assays showed that the TAD of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with Mediator 25 in human melanoma MeWo cells. The SRT of IE62 interacted with the nucleolar-ribosomal protein EAP, which resulted in the formation of globular structures within the nucleus. These results suggest that the SRT plays an important role in VZV viral gene expression and replication. IMPORTANCE The immediate early 62 protein (IE62) of varicella-zoster virus (VZV) is a major viral trans-activator and is essential for viral growth. Our data show that the serine-rich tract (SRT) of VZV IE62, which is well conserved within the alphaherpesviruses, is needed for trans-activation mediated by the acidic trans-activation domain (TAD). The TADs of IE62

Stress-Induced Subclinical Reactivation of Varicella Zoster Virus in Astronauts

NASA Technical Reports Server (NTRS)

Mehta, Satish K.; Pierson, Duane L.; Forghani, Bagher; Zerbe, Gary; Cohrs, Randall J.; Gilden, Donald H.

2003-01-01

After primary infection, varicella-zoster virus (VZV) becomes latent in ganglia. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell-mediated immunity to VZV. VZV can also reactivate after surgical stress. To determine whether VZV can also reactivate after acute non-surgical stress, we examined total DNA extracted from 312 saliva samples of eight astronauts before, during and after space flight for VZV DNA by PCR: 112 samples were obtained 234 to 265 days before flight, 84 samples on days 2 through 13 of space flight, and 116 samples on days 1 through 15 after flight. Before space flight only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples were positive in all 8 astronauts. No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These data indicate that VZV can reactivate subclinically in healthy individuals after acute stress.

Novel polyvalent live vaccine against varicella-zoster and mumps virus infections.

PubMed

Matsuura, Masaaki; Somboonthum, Pranee; Murakami, Kouki; Ota, Megumi; Shoji, Masaki; Kawabata, Kenji; Mizuguchi, Hiroyuki; Gomi, Yasuyuki; Yamanishi, Koichi; Mori, Yasuko

2013-10-01

The varicella-zoster virus (VZV) Oka vaccine strain (vOka) is a highly immunogenic and safe live vaccine that has long been used worldwide. Because its genome is large, making it suitable for inserting foreign genes, vOka is considered a candidate vector for novel polyvalent vaccines. Previously, a recombinant vOka, rvOka-HN, that expresses mumps virus (MuV) hemagglutinin-neuraminidase (HN) was generated by the present team. rvOka-HN induces production of neutralizing antibodies against MuV in guinea pigs. MuV also expresses fusion (F) protein, which is important for inducing neutralizing antibodies, in its viral envelope. To induce a more robust immune response against MuV than that obtained with rvOka-HN, here an rvOka expressing both HN and F (rvOka-HN-F) was generated. However, co-expression of HN and F caused the infected cells to form syncytia, which reduced virus titers. To reduce the amount of cell fusion, an rvOka expressing HN and a mutant F, F(S195Y) were generated. Almost no syncytia formed among the rvOka-HN-F(S195Y)-infected cells and the growth of rvOka-HN-F(S195Y) was similar to that of the original vOka clone. Moreover, replacement of serine 195 with tyrosine had no effect on the immunogenicity of F in mice and guinea pigs. Although obvious augmentation of neutralizing antibody production was not observed after adding F protein to vOka-HN, the anti-F antibodies did have neutralizing activity. These data suggest that F protein contributes to induction of immune protection against MuV. Therefore this recombinant virus is a promising candidate vaccine for polyvalent protection against both VZV and MuV. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

HERPES ZOSTER FOLLOWING ROENTGEN IRRADIATION (in Hungarian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vetro, E.

1963-06-01

This report describes the appearance of herpes zoster in six female patients following x irradiation therapy with total doses of 1400 to 3000 r. Five of the patients received the treatment as postoperative treatment for breast cancer, the sixth patient was treated for rheumatoid anthritis. It is noted that this occurrence of herpes zoster following postoperative irradiation treatment for breast cancer is 100 times its incidence in the normal population where it occurs in an average of 0.025%. In the cases described, herpes appeared on the irradiated side of the body, in one instance it was very severe in amore » patient who had received prior hydrocortisone treatment, which might have accounted for the herpes in this case. It is possible that the herpes virus entered through the incision caused by the operation on the breast, although this has not been proven. The frequent occurrence of herpes zoster following irradiation is not coincidental, and further studies are under way, including measurements of radiation damage to the spinal cord ganglia. (BBB)« less

Herpes Zoster Risk Reduction through Exposure to Chickenpox Patients: A Systematic Multidisciplinary Review.

PubMed

Ogunjimi, Benson; Van Damme, Pierre; Beutels, Philippe

2013-01-01

Varicella-zoster virus (VZV) causes chickenpox and may subsequently reactivate to cause herpes zoster later in life. The exogenous boosting hypothesis states that re-exposure to circulating VZV can inhibit VZV reactivation and consequently also herpes zoster in VZV-immune individuals. Using this hypothesis, mathematical models predicted widespread chickenpox vaccination to increase herpes zoster incidence over more than 30 years. Some countries have postponed universal chickenpox vaccination, at least partially based on this prediction. After a systematic search and selection procedure, we analyzed different types of exogenous boosting studies. We graded 13 observational studies on herpes zoster incidence after widespread chickenpox vaccination, 4 longitudinal studies on VZV immunity after re-exposure, 9 epidemiological risk factor studies, 7 mathematical modeling studies as well as 7 other studies. We conclude that exogenous boosting exists, although not for all persons, nor in all situations. Its magnitude is yet to be determined adequately in any study field.

Herpes Zoster Risk Reduction through Exposure to Chickenpox Patients: A Systematic Multidisciplinary Review

PubMed Central

Ogunjimi, Benson; Van Damme, Pierre; Beutels, Philippe

2013-01-01

Varicella-zoster virus (VZV) causes chickenpox and may subsequently reactivate to cause herpes zoster later in life. The exogenous boosting hypothesis states that re-exposure to circulating VZV can inhibit VZV reactivation and consequently also herpes zoster in VZV-immune individuals. Using this hypothesis, mathematical models predicted widespread chickenpox vaccination to increase herpes zoster incidence over more than 30 years. Some countries have postponed universal chickenpox vaccination, at least partially based on this prediction. After a systematic search and selection procedure, we analyzed different types of exogenous boosting studies. We graded 13 observational studies on herpes zoster incidence after widespread chickenpox vaccination, 4 longitudinal studies on VZV immunity after re-exposure, 9 epidemiological risk factor studies, 7 mathematical modeling studies as well as 7 other studies. We conclude that exogenous boosting exists, although not for all persons, nor in all situations. Its magnitude is yet to be determined adequately in any study field. PMID:23805224

The burden of hospitalisation for varicella and herpes zoster in England from 2004 to 2013.

PubMed

Hobbelen, Peter H F; Stowe, Julia; Amirthalingam, Gayatri; Miller, Liz; van Hoek, Albert-Jan

2016-09-01

We aimed to determine the hospital burden of varicella-zoster virus infection (VZV) in England during 2004-2013 to support a future cost-effectiveness analysis of a childhood varicella vaccination programme. We analysed the incidence, duration, outcome and costs of hospitalisations for VZV using the Hospital Episode Statistics (HES) database for the general and immunocompetent population. Mortality in HES was validated using data from the Office for National Statistics (ONS). The average annual incidences of admissions due to varicella and herpes zoster were 7.6 (7.3-7.9) and 8.8 (8.6-9.0) per 100,000, respectively. The immunocompetent population accounted for 93% and 82% of the admissions due to varicella and herpes zoster, respectively. The average yearly number of hospital days was 10,748 (10,227-11,234) for varicella and 41,780 (40,257-43,287) for herpes zoster. The average yearly hospital costs (£2013/14) were £6.8 million (6.4-7.2) for varicella and £13.0 million (12.8-13.4) for herpes zoster. The average annual numbers of deaths identified in HES due to varicella and herpes zoster were 18.5 (14.3-22.8) and 160 (147-172), respectively. Comparison with ONS mortality data indicated a high level of uncertainty. Most of the hospital burden due to VZV-virus in England occurs in the immunocompetent population and is potentially vaccine-preventable. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Challenges in designing a Taqman-based multiplex assay for the simultaneous detection of Herpes simplex virus types 1 and 2 and Varicella-zoster virus.

PubMed

Weidmann, Manfred; Armbruster, Katrin; Hufert, Frank T

2008-08-01

To optimise molecular detection of herpesviruses an internally controlled multiplex Taqman-PCR for the detection of Herpes simplex virus 1 (HSV1), Herpes simplex virus 2 (HSV2) and Varicella-zoster virus (VZV) was developed. The selection of the dye combination working on the ABI 7700 cycler for this multiplex PCR revealed crosstalk phenomena between several combinations of reference dyes and reporter dyes. A final dye combination with CY5 as reference dye and FAM/JOE/TXR as reporter dyes was selected. The influence of the concentration of the internal positive control (IPC) concentration on the quantitative results of HSV1, HSV2 and VZV positive patient samples was analysed. The results indicate that high IPC concentrations are detrimental for the sensitivity of the multiplex assay and that the presence of the IPC molecule narrows the dynamic range of the duplex PCRs between any of the virus PCRs and the IPC-PCR. The optimised multiplex assay detecting HSV1, HSV2 and VZV using 10(3) IPC molecules showed a performance and sensitivity comparable to that of the individual assays.

Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression.

PubMed

Leuvenink, Raphael; Aeschlimann, Florence; Baer, Walter; Berthet, Gerald; Cannizzaro, Elvira; Hofer, Michael; Kaiser, Daniela; Schroeder, Silke; Heininger, Ulrich; Woerner, Andreas

2016-06-02

To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. Retrospective multicenter study using the Swiss Pediatric Rheumatology registry. Children with rheumatic diseases followed in a Swiss center for pediatric rheumatology and treated with cDMARD and/or bDMARD with a clinical diagnosis of varicella or herpes zoster between January 2004 and December 2013 were included. Twenty-two patients were identified, of whom 20 were treated for juvenile idiopathic arthritis, 1 for a polyglandular autoimmune syndrome type III, and 1 for uveitis. Of these 22 patients, 16 had varicella and 6 had herpes zoster. Median age at VZV disease was 7.6 years (range 2 to 17 years), with 6.3 years (range 2 to 17 years) for those with varicella and 11.6 years (range 5 to 16 years) for those with herpes zoster. The median interval between start of immunosuppression and VZV disease was 14.1 months (range 1 to 63 months). Two patients had received varicella vaccine (1 dose each) prior to start of immunosuppression. Concomitant immunosuppressive therapy was methotrexate (MTX) monotherapy (n = 9) or bDMARD monotherapy (n = 2), or a combination of bDMARD with prednisone, MTX or Leflunomide (n = 11). Four patients experienced VZV related complications: cellulitis in 1 patient treated with MTX, and cellulitis, sepsis and cerebellitis in 3 patients treated with biological agents and MTX combination therapy. Six children were admitted to hospital (range of duration: 4 to 9 days) and 12 were treated with valaciclovir or aciclovir. The clinical course of varicella and herpes zoster in children under

Novel approach to differentiate subclades of varicella-zoster virus genotypes E1 and E2 in Germany.

PubMed

Schmidt-Chanasit, Jonas; Olschläger, Stephan; Bialonski, Alexandra; Heinemann, Patrick; Bleymehl, Karoline; Gross, Gerd; Günther, Stephan; Ulrich, Rainer G; Doerr, Hans Wilhelm

2009-11-01

Varicella-zoster virus (VZV) is the causative agent of chicken pox (varicella) in children and reactivation of VZV in elderly or immunocompromised persons can cause shingles (zoster). A subclade differentiation of the most prevalent VZV genotypes E1 and E2 in Germany was not possible with the current genotyping methods in use, but is highly important to understand the VZV molecular evolution in more detail and especially to follow up the routes of infection. Therefore the objective of this study was to develop a simple PCR-based method for differentiation of E1 and E2 subclades. Viral DNA was isolated from vesicle fluid samples of six selected German zoster patients and used to amplify nine complete open reading frames (ORFs) of the VZV genome by different PCR assays. Phylogenetic analysis was performed by a Bayesian approach. Based on the analysis of a total of nine ORFs, a 7482 bp stretch consisting of ORFs 5, 37 and 62 contained informative sites for identification of novel subclades E1a, E2a and E2b for VZV genotypes E1 and E2. Specific single nucleotide polymorphisms (SNPs) were demonstrated for subclades E2a and E2b within the ORFs 5, 37 and 62, whereas a subclade E1a-specific SNP was found in ORF 56. The classification of E1 and E2 subclades may facilitate a more exact and in-depth monitoring of the molecular evolution of VZV in Germany in the future.

Herpes zoster vaccine. Poorly effective in those who need it most.

PubMed

2012-12-01

The results of a clinical trial suggest that zoster vaccination (Zostavax, Sanofi Pasteur MSD) of 1000 healthy persons aged 60 years or over prevents approximately one case of postherpetic neuralgia each year over the next 3 years. Vaccination is less effective in persons over 70 years of age. The results of another clinical trial suggest that vaccination of 1000 healthy persons aged 50 to 59 years prevents about 5 cases of herpes zoster over the following year. The impact on the frequency of postherpetic neuralgia is not known. The vaccine might not be protective in persons who subsequently become immunocompromised. In the trial in persons aged 50 years or older, 50% of vaccinees had mild local adverse effects. It should be noted that the protocol excluded immunocompromised patients, in whom the live vaccine virus could potentially cause clinically significant infection. In one study, the immune response to the vaccine was lower after simultaneous immunisation with a 23-valent pneumococcal polysaccharide vaccine. This live zoster vaccine is contraindicated in immunocompromised individuals, yet they are at highest risk of severe zoster. In practice, zoster vaccination is not sufficiently effective in the elderly to justify its widespread use.

Detection of herpes simplex virus and varicella-zoster virus in clinical swabs: frequent inhibition of PCR as determined by internal controls.

PubMed

Bezold, G; Volkenandt, M; Gottlöber, P; Peter, R U

2000-12-01

PCR-based detection of microorganisms is widely used for diagnostic purposes. Most routine PCR applications do not control for inhibition of PCR, thus leading to false-negative results. One hundred eighteen swab samples obtained from skin and mucosa were investigated for the presence of herpes simplex virus (HSV), varicella-zoster virus (VZV), and the control gene betaglobin by internally controlled PCR with purified and unpurified DNA in parallel. With unpurified DNA, inhibition of PCR was detected in 23% of betaglobin PCRs, 25% of VZV PCRs, and 16% of HSV PCRs versus 3% each for purified DNA. Approximately 20% of the samples with positive results for HSV or VZV had negative or inhibited results using unpurified DNA. These results indicate that PCR from clinical swab specimens should be performed exclusively with internal controls because the positive control alone cannot exclude PCR inhibition in individual samples. Purification of DNA will decrease, but not exclude, PCR inhibition.

Interactome Networks and Human Disease

PubMed Central

Vidal, Marc; Cusick, Michael E.; Barabási, Albert-László

2011-01-01

Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease. PMID:21414488

[Neurological complications among patients with zoster hospitalized in Department of Infectious Diseases in Cracow in 2001-2006].

PubMed

Biesiada, Grazyna; Czepiel, Jacek; Sobczyk-Krupiarz, Iwona; Mach, Tomasz; Garlicki, Aleksander

2010-01-01

Herpes zoster is an infectious disease caused by varicella zoster virus (VZV). After replication at the place of entry, VZV spreads via the blood into the skin and mucosa, causing the varicella. From these regions VZV migrates into the sensory ganglia where it establishes a latent infection. The aim of our study was to analyze the localization of the skin changes and correlations of neurological complications among patient with zoster. We have reviewed medical documentation of the 67 patients with herpes zoster, hospitalized in our Department during the years 2001-2006. We have studied localization of the herpes zoster changes and frequency of neurological complications among these patients. Neuralgia was less intensive and last shorter time, when antiviral treatment had been started earlier. Neuralgia, meningitis, encephalitis and complications of the eye zoster were present more often among patients over 65 years old.

Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster.

PubMed

Kim, Choon Kwan; Choi, Youn Mi; Bae, Eunsin; Jue, Mihn Sook; So, Hyung Seok; Hwang, Eung-Soo

2018-01-01

The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma secretion from natural killer cell and psychological stress were not associated. In conclusion, patients with a recent diagnosis of herpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster.

Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster

PubMed Central

Kim, Choon Kwan; Choi, Youn Mi; Bae, Eunsin; Jue, Mihn Sook; So, Hyung Seok

2018-01-01

The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma secretion from natural killer cell and psychological stress were not associated. In conclusion, patients with a recent diagnosis of herpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster. PMID:29466462

Live attenuated herpes zoster vaccine for HIV-infected adults.

PubMed

Shafran, S D

2016-04-01

Multiple guidelines exist for the use of live viral vaccines for measles-mumps-rubella (MMR), varicella and yellow fever in people with HIV infections, but these guidelines do not make recommendations regarding live attenuated herpes zoster vaccine (LAHZV), which is approved for people over 50 years in the general population. LAHZV is made with the same virus used in varicella vaccine. The incidence of herpes zoster remains increased in people with HIV infection, even when on suppressive antiretroviral therapy, and a growing proportion of HIV-infected patients are over 50 years of age. The purpose of this article is to review the use of varicella vaccine and LAHZV in people with HIV infection and to make recommendations about the use of LAHZV in adults with HIV infection. A PubMed search was undertaken using the terms 'herpes zoster AND HIV' and 'varicella AND HIV'. Reference lists were also reviewed for pertinent citations. Varicella vaccine is recommended in varicella-susceptible adults, as long as they have a CD4 count > 200 cells/μL, the same CD4 threshold used for MMR and yellow fever vaccines. No transmission of vaccine strain Varicella zoster virus has been documented in people with HIV infections with a CD4 count above this threshold. LAHZV was administered to 295 HIV-infected adults with a CD4 count > 200 cells/μL, and was safe and immunogenic with no cases of vaccine strain infection. It is recommended that LAHZV be administered to HIV-infected adults with a CD4 count above 200 cells/μL, the same CD4 threshold used for other live attenuated viral vaccines. © 2015 British HIV Association.

Serological Evaluation of Immunity to the Varicella-Zoster Virus Based on a Novel Competitive Enzyme-Linked Immunosorbent Assay

PubMed Central

Liu, Jian; Ye, Xiangzhong; Jia, Jizong; Zhu, Rui; Wang, Lina; Chen, Chunye; Yang, Lianwei; Wang, Yongmei; Wang, Wei; Ye, Jianghui; Li, Yimin; Zhu, Hua; Zhao, Qinjian; Cheng, Tong; Xia, Ningshao

2016-01-01

Varicella-zoster virus (VZV) is a highly contagious agent of varicella and herpes zoster. Varicella can be lethal to immunocompromised patients, babies, HIV patients and other adults with impaired immunity. Serological evaluation of immunity to VZV will help determine which individuals are susceptible and evaluate vaccine effectiveness. A collection of 110 monoclonal antibodies (mAbs) were obtained by immunization of mice with membrane proteins or cell-free virus. The mAbs were well characterized, and a competitive sandwich ELISA (capture mAb: 8H6; labelling mAb: 1B11) was established to determine neutralizing antibodies in human serum with reference to the FAMA test. A total of 920 human sera were evaluated. The competitive sandwich ELISA showed a sensitivity of 95.6%, specificity of 99.77% and coincidence of 97.61% compared with the fluorescent-antibody-to-membrane-antigen (FAMA) test. The capture mAb 8H6 was characterized as a specific mAb for VZV ORF9, a membrane-associated tegument protein that interacts with glycoprotein E (gE), glycoprotein B (gB) and glycoprotein C (gC). The labelling mAb 1B11 was characterized as a complement-dependent neutralizing mAb specific for the immune-dominant epitope located on gE, not on other VZV glycoproteins. The established competitive sandwich ELISA could be used as a rapid and high-throughput method for evaluating immunity to VZV. PMID:26853741

Helicase-primase inhibitor amenamevir for herpesvirus infection: Towards practical application for treating herpes zoster.

PubMed

Shiraki, K

2017-11-01

Valacyclovir and famciclovir enabled successful systemic therapy for treating herpes simplex virus (HSV) and varicella zoster virus (VZV) infection by their phosphorylation with viral thymidine kinase. Helicase-primase inhibitors (HPIs) inhibit the progression of the replication fork, an initial step in DNA synthesis to separate the double strand into two single strands. The HPIs amenamevir and pritelivir have a novel mechanism of action, once-daily administration with nonrenal excretory characteristics, and clinical efficacy for genital herpes. Amenamevir exhibits anti-VZV and anti-HSV activity while pritelivir only has anti-HSV activity. A clinical trial of amenamevir for herpes zoster has been completed, and amenamevir has been licensed and successfully used in 20,000 patients with herpes zoster so far in Japan. We have characterized the features of the antiviral action of amenamevir and, unlike acyclovir, the drug's antiviral activity is not influenced by the viral replication cycle. Amenamevir is opening a new era of antiherpes therapy. Copyright 2017 Clarivate Analytics.

Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

PubMed

Cho, Bum-Joo; Kim, Ji-Soo; Hwang, Jeong-Min

2013-12-01

A 55-year-old woman presented with diplopia following painful skin eruptions on the right upper extremity. On presentation, she was found to have 35 prism diopters of esotropia and an abduction limitation in the left eye. Two weeks later, she developed blepharoptosis and anisocoria with a smaller pupil in the right eye, which increased in the darkness. Cerebrospinal fluid analysis showed pleocytosis and a positive result for immunoglobulin G antibody to varicella zoster virus. She was diagnosed to have zoster meningitis with Horner's syndrome and contralateral abducens nerve palsy. After intravenous antiviral and steroid treatments, the vesicular eruptions and abducens nerve palsy improved. Horner's syndrome and diplopia resolved after six months. Here we present the first report of Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

Safety of Zoster Vaccine in Elderly Adults Following Documented Herpes Zoster

PubMed Central

Morrison, Vicki A.; Oxman, Michael N.; Levin, Myron J.; Schmader, Kenneth E.; Guatelli, John C.; Betts, Robert F.; Gelb, Larry D.; Pachucki, Constance T.; Keay, Susan K.; Menzies, Barbara; Griffin, Marie R.; Kauffman, Carol A.; Marques, Adriana R.; Toney, John F.; Simberkoff, Michael S.; Serrao, Richard; Arbeit, Robert D.; Gnann, John W.; Greenberg, Richard N.; Holodniy, Mark; Keitel, Wendy A.; Yeh, Shingshing S.; Davis, Larry E.; Crawford, George E.; Neuzil, Kathy M.; Johnson, Gary R.; Zhang, Jane H.; Harbecke, Rith; Chan, Ivan S. F.; Keller, Paul M.; Williams, Heather M.; Boardman, Kathy D.; Silber, Jeffrey L.; Annunziato, Paula W.

2013-01-01

Background. After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). Methods. A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. Results. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3–85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. Conclusions. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥60 years of age with no contraindications, regardless of a prior history of HZ. PMID:23633406

Safety of zoster vaccine in elderly adults following documented herpes zoster.

PubMed

Morrison, Vicki A; Oxman, Michael N; Levin, Myron J; Schmader, Kenneth E; Guatelli, John C; Betts, Robert F; Gelb, Larry D; Pachucki, Constance T; Keay, Susan K; Menzies, Barbara; Griffin, Marie R; Kauffman, Carol A; Marques, Adriana R; Toney, John F; Simberkoff, Michael S; Serrao, Richard; Arbeit, Robert D; Gnann, John W; Greenberg, Richard N; Holodniy, Mark; Keitel, Wendy A; Yeh, Shingshing S; Davis, Larry E; Crawford, George E; Neuzil, Kathy M; Johnson, Gary R; Zhang, Jane H; Harbecke, Rith; Chan, Ivan S F; Keller, Paul M; Williams, Heather M; Boardman, Kathy D; Silber, Jeffrey L; Annunziato, Paula W

2013-08-15

After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3-85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥ 1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥ 60 years of age with no contraindications, regardless of a prior history of HZ.

Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease.

PubMed

Tseng, Hung Fu; Smith, Ning; Harpaz, Rafael; Bialek, Stephanie R; Sy, Lina S; Jacobsen, Steven J

2011-01-12

Approximately 1 million episodes of herpes zoster occur annually in the United States. Although prelicensure data provided evidence that herpes zoster vaccine works in a select study population under idealized circumstances, the vaccine needs to be evaluated in field conditions. To evaluate risk of herpes zoster after receipt of herpes zoster vaccine among individuals in general practice settings. A retrospective cohort study from January 1, 2007, through December 31, 2009, of individuals enrolled in the Kaiser Permanente Southern California health plan. Participants were immunocompetent community-dwelling adults aged 60 years or older. The 75,761 members in the vaccinated cohort were age matched (1:3) to 227,283 unvaccinated members. Incidence of herpes zoster. Herpes zoster vaccine recipients were more likely to be white, women, with more outpatient visits, and fewer chronic diseases. The number of herpes zoster cases among vaccinated individuals was 828 in 130,415 person-years (6.4 per 1000 person-years; 95% confidence interval [CI], 5.9-6.8), and for unvaccinated individuals it was 4606 in 355,659 person-years (13.0 per 1000 person-years; 95% CI, 12.6-13.3). In adjusted analysis, vaccination was associated with a reduced risk of herpes zoster (hazard ratio [HR], 0.45; 95% CI, 0.42-0.48); this reduction occurred in all age strata and among individuals with chronic diseases. Risk of herpes zoster differed by vaccination status to a greater magnitude than the risk of unrelated acute medical conditions, suggesting results for herpes zoster were not due to bias. Ophthalmic herpes zoster (HR, 0.37; 95% CI, 0.23-0.61) and hospitalizations coded as herpes zoster (HR, 0.35; 95% CI, 0.24-0.51) were less likely among vaccine recipients. Among immunocompetent community-dwelling adults aged 60 years or older, receipt of the herpes zoster vaccine was associated with a lower incidence of herpes zoster. The risk was reduced among all age strata and among individuals with

Sex differences underlying orofacial varicella zoster associated pain in rats.

PubMed

Stinson, Crystal; Deng, Mohong; Yee, Michael B; Bellinger, Larry L; Kinchington, Paul R; Kramer, Phillip R

2017-05-17

Most people are initially infected with varicella zoster virus (VZV) at a young age and this infection results in chickenpox. VZV then becomes latent and reactivates later in life resulting in herpes zoster (HZ) or "shingles". Often VZV infects neurons of the trigeminal ganglia to cause ocular problems, orofacial disease and occasionally a chronic pain condition termed post-herpetic neuralgia (PHN). To date, no model has been developed to study orofacial pain related to varicella zoster. Importantly, the incidence of zoster associated pain and PHN is known to be higher in women, although reasons for this sex difference remain unclear. Prior to this work, no animal model was available to study these sex-differences. Our goal was to develop an orofacial animal model for zoster associated pain which could be utilized to study the mechanisms contributing to this sex difference. To develop this model VZV was injected into the whisker pad of rats resulting in IE62 protein expression in the trigeminal ganglia; IE62 is an immediate early gene in the VZV replication program. Similar to PHN patients, rats showed retraction of neurites after VZV infection. Treatment of rats with gabapentin, an agent often used to combat PHN, ameliorated the pain response after whisker pad injection. Aversive behavior was significantly greater for up to 7 weeks in VZV injected rats over control inoculated rats. Sex differences were also seen such that ovariectomized and intact female rats given the lower dose of VZV showed a longer affective response than male rats. The phase of the estrous cycle also affected the aversive response suggesting a role for sex steroids in modulating VZV pain. These results suggest that this rat model can be utilized to study the mechanisms of 1) orofacial zoster associated pain and 2) the sex differences underlying zoster associated pain.

[S1 Herpes zoster localization: acute urinary retention in woman].

PubMed

Vella, Marco; Mastrocinque, Giuseppe; Romeo, Salvatore; Giammanco, Giovanni; Melloni, Darwin

2011-01-01

Acute urinary retention in women is rare. The varicella-zoster virus causes inflammatory lesions of the sensory-root ganglions, meninges and, less frequently, spinal cord. Herpes zoster has been reported to affect, although rarely, lower urinary tract innervations, and acute urinary retention can be thought to occur in the presence of sacral dermatome involvement. Usually it is located in S2-4 dermatome and the prognosis for acute urinary retention is benign resolving in about 20 days. We present a case in which the S1 dermatome was involved and acute urinary retention developed. After 10 days of specific therapy and self-catheterization the problem resolved.

Long Term Persistence of IgE Anti-Varicella Zoster Virus in Pediatric and Adult Serum Post Chicken Pox Infection and after Vaccination with Varicella Virus Vaccine.

PubMed

Smith-Norowitz, Tamar A; Josekutty, Joby; Silverberg, Jonathan I; Lev-Tov, Hadar; Norowitz, Yitzchok M; Kohlhoff, Stephan; Nowakowski, Maja; Durkin, Helen G; Bluth, Martin H

2009-12-01

The production of IgE specific to different viruses (HIV-1, Parvovirus B19, RSV), and the ability for IgE anti-HIV-1 to suppress HIV-1 production in vitro, strongly suggest an important role for IgE and/or anti viral specific IgE in viral pathogenesis. Previous studies in our laboratory were the first to report the presence of IgE anti-varicella zoster virus (VZV) in an adolescent patient with shingles. However, the presence and long term persistence of IgE anti VZV antibodies has not been studied in adults. The presence of serum IgE in addition to IgE and IgG anti-VZV antibody in sera were studied in children (N=12) (0-16 y/o) and adults (N=9) (32-76 y/o) with either a past history of (wild type) chicken pox (N=7 children, 9 adults) or 5 years after vaccination with varicella zoster (N=2 children) (Varicella virus vaccine live, Oka/Merck), as well as in non-infected subjects (N=3 children). Of the patients who had a positive history of chicken pox 13 of 16 (81%) contained IgE anti-VZV antibodies; they were both serum IgEHi (>100 IU/ml) and IgELo (<100 IU/ml). Of the patients who were vaccinated, IgE anti-VZV antibodies were undetected. In contrast, serum from the patients without a history of chicken pox or vaccination did not make either IgE or IgG anti-VZV antibodies. This is the first demonstration of the existence of IgE anti-VZV antibodies, and its long-term persistence in serum of previously infected subjects. Future studies regarding the functional role of anti-viral IgE and its relationship to VZV are warranted.

A Rare Presentation of Cranial Polyneuropathy Without Rash Caused by Varicella Zoster Virus

PubMed Central

Tecellioglu, Mehmet; Kamisli, Suat; Erbay, Mehmet Fatih; Kamisli, Ozden; Ozcan, Cemal

2017-01-01

Introduction: Varicella Zoster Virus (VZV) is associated with many disorders of the central and peripheral nervous systems including neuralgia, meningitis, meningoencephalitis, cerebellitis, vasculopathy, myelopathy, Ramsay-Hunt syndrome, and polyneuritis cranialis. Cranial nerves V, VI, VII, VIII, IX, X, XI, and/or XII may be affected. The neurological disorders caused by VZV usually present with rash, but may rarely present without rash. Case report: We herein present a case of polyneuritis cranialis without rash caused by VZV affecting cranial nerves VII, VIII, IX, and X. After excluding other causes of the condition, we diagnosed VZV infection based on VZV DNA in the CSF and an elevated anti-VZV IgG level in serum. The patient responded well to antiviral therapy. Conclusion: VZV infection should be kept in mind during the differential diagnosis of polyneuritis cranialis; it is important to note that VZV re-activation may occur without rash. PMID:28974853

Protection From Varicella Zoster in Solid Organ Transplant Recipients Carrying Killer Cell Immunoglobulin-Like Receptor B Haplotypes.

PubMed

Schmied, Laurent; Terszowski, Grzegorz; Gonzalez, Asensio; Schmitter, Karin; Hirsch, Hans H; Garzoni, Christian; van Delden, Christian; Boggian, Katia; Mueller, Nicolas J; Berger, Christoph; Villard, Jean; Manuel, Oriol; Meylan, Pascal; Hess, Christoph; Stern, Martin

2015-12-01

Natural killer cell function is regulated by inhibitory and activating killer cell immunoglobulin-like receptors (KIR). Previous studies have documented associations of KIR genotype with the risk of cytomegalovirus (CMV) replication after solid organ transplantation. In this study of 649 solid organ transplant recipients, followed prospectively for infectious disease events within the Swiss Transplant Cohort Study, we were interested to see if KIR genotype associated with virus infections other than CMV. We found that KIR B haplotypes (which have previously been linked to protection from CMV replication) were associated with protection from varicella zoster virus infection (hazard ratio, 0.43; 95% confidence interval, 0.21-0.91; P = 0.03). No significant associations were detected regarding the risk of herpes simplex, Epstein-Barr virus or BK polyomavirus infections. In conclusion, these data provide evidence that the relative protection of KIR haplotype B from viral replication after solid organ transplantation may extend beyond CMV to other herpes viruses, such as varicella zoster virus and possibly Epstein-Barr virus.

Does monastic life predispose to the risk of Saint Anthony's fire (herpes zoster)?

PubMed

Gaillat, Jacques; Gajdos, Vincent; Launay, Odile; Malvy, Denis; Demoures, Bruno; Lewden, Lucie; Pinchinat, Sybil; Derrough, Tarik; Sana, Claudine; Caulin, Evelyne; Soubeyrand, Benoît

2011-09-01

The consequences of the epidemiology of varicella for zoster epidemiology are still debated. We therefore compared the frequency of herpes zoster in an adult population with virtually no varicella zoster virus (VZV) exposure with that in the general population (GP). We performed a national, multicenter, observational, exposed versus nonexposed, comparative study. The nonexposed population consisted of members of contemplative monastic orders (CMO) of the Roman Catholic Church living in 40 isolated monasteries in France. The exposed population consisted of a sample of the GP representative of the French population in terms of age group, sex, socio-occupational categories, and regions. The primary analysis population comprised 920 members of CMO (41.5% nuns; mean age, 64.2 years) and 1533 members of the GP (51.9% women; mean age, 64.6 years). The reported frequency of zoster was 16.2% among CMO and 15.1% in the GP (P = .27, adjusted for sex and age). The reported mean age of onset of zoster was 54.8 and 48.6 years, respectively (P = .06). This study failed to demonstrate an increased risk or earlier onset of zoster in members of CMO not exposed to VZV, compared with that in the GP. Although adults highly exposed to VZV could have a reduced risk of zoster, compared with the GP, our results suggest that the opposite is not true: adults not exposed to VZV are not at increased risk of zoster when compared with the GP, challenging the relevance of the assumptions and forecasts of current epidemiological models.

Risk of depressive disorder among patients with herpes zoster: a nationwide population-based prospective study.

PubMed

Chen, Mu-Hong; Wei, Han-Ting; Su, Tung-Ping; Li, Cheng-Ta; Lin, Wei-Chen; Chang, Wen-Han; Chen, Tzeng-Ji; Bai, Ya-Mei

2014-05-01

Herpes zoster results from reactivation of the endogenous varicella zoster virus infection. Previous studies have shown that herpes zoster and postherpetic neuralgia were associated with anxiety, depression, and insomnia. However, no prospective study has investigated the association between herpes zoster and the development of depressive disorder. Subjects were identified through the Taiwan National Health Insurance Research Database. Patients 18 years or older with a diagnosis of herpes zoster and without a psychiatric history were enrolled in 2000 and compared with age-/sex-matched controls (1:4). These participants were followed up to the end of 2010 for new-onset depressive disorder. A total of 1888 patients with herpes zoster were identified and compared with 7552 age-/sex-matched controls in 2000. Those with herpes zoster had a higher incidence of developing major depression (2.2% versus 1.4%, p = .018) and any depressive disorder (4.3% versus 3.2%, p = .020) than did the control group. The follow-up showed that herpes zoster was an independent risk factor for major depression (hazard ratio = 1.49, 95% confidence interval = 1.04-2.13) and any depressive disorder (hazard ratio = 1.32, 95% confidence interval = 1.03-1.70), after adjusting demographic data and comorbid medical diseases. This is the first study to investigate the temporal association between herpes zoster and depressive disorder. Further studies would be required to clarify the underlying pathophysiology about this association and whether proper treatment of herpes zoster could decrease the long-term risk of depressive disorder.

An "on-matrix" digestion procedure for AP-MS experiments dissects the interplay between complex-conserved and serotype-specific reactivities in Dengue virus-human plasma interactome.

PubMed

Ramos, Yassel; Huerta, Vivian; Martín, Dayron; Palomares, Sucel; Yero, Alexis; Pupo, Dianne; Gallien, Sebastien; Martín, Alejandro M; Pérez-Riverol, Yasset; Sarría, Mónica; Guirola, Osmany; Chinea, Glay; Domon, Bruno; González, Luis Javier

2017-07-13

The interactions between the four Dengue virus (DENV) serotypes and plasma proteins are crucial in the initial steps of viral infection to humans. Affinity purification combined with quantitative mass spectrometry analysis, has become one of the most powerful tools for the investigation on novel protein-protein interactions. Using this approach, we report here that a significant number of bait-interacting proteins do not dissociate under standard elution conditions, i.e. acid pH and chaotropic agents, and that this problem can be circumvented by using the "on-matrix" digestion procedure described here. This procedure enabled the identification of 16 human plasma proteins interacting with domain III from the envelope protein of DENV serotypes 1, 3 and 4 that would have not been detected otherwise and increased the known DIIIE interactors in human plasma to 59 proteins. Selected Reaction Monitoring analysis evidenced DENV interactome in human plasma is rather conserved although significant differences on the reactivity of viral serotypes with specific proteins do exist. A comparison between the serotype-dependent profile of reactivity and the conservation pattern of amino acid residues suggests an evolutionary selection of highly conserved interactions with the host and other interactions mediated for surface regions of higher variability. False negative results on the identification of interacting proteins in pull-down experiments compromise the subsequent interpretation of results and the formulation of a working hypothesis for the derived future work. In this study we demonstrate the presence of bait-interacting proteins reluctant to dissociate under elution conditions of acid pH and presence of chaotropics. We propose the direct proteolytic digestion of proteins while still bound to the affinity matrix ("on-matrix" digestion) and evaluate the impact of this methodology in the comparative study of the interactome of the four serotypes of Dengue virus mediated by

Rearrangement of the Protein Phosphatase 1 Interactome During Heart Failure Progression.

PubMed

Chiang, David Y; Alsina, Katherina M; Corradini, Eleonora; Fitzpatrick, Martin; Ni, Li; Lahiri, Satadru K; Reynolds, Julia; Pan, Xiaolu; Scott, Larry; Heck, Albert J R; Wehrens, Xander H

2018-04-18

Background -Heart failure (HF) is a complex disease with a rising prevalence despite advances in treatment. Protein phosphatase 1 (PP1) has long been implicated in HF pathogenesis but its exact role is both unclear and controversial. Most previous studies measured only the PP1 catalytic subunit (PP1c) without investigating its diverse set of interactors, which confer localization and substrate specificity to the holoenzyme. In this study we define the PP1 interactome in cardiac tissue and test the hypothesis that this interactome becomes rearranged during HF progression at the level of specific PP1c interactors. Methods -Mice were subjected to transverse aortic constriction and grouped based on ejection fraction (EF) into sham, hypertrophy, moderate HF (EF 30-40%), and severe HF (EF<30%). Cardiac lysates were subjected to affinity-purification using anti-PP1c antibodies followed by high-resolution mass spectrometry. Ppp1r7 was knocked down in mouse cardiomyocytes and HeLa cells using adeno-associated virus serotype 9 (AAV9) and siRNA, respectively. Calcium imaging was performed on isolated ventricular myocytes. Results -Seventy-one and 98 PP1c interactors were quantified from mouse cardiac and HeLa lysates, respectively, including many novel interactors and protein complexes. This represents the largest reproducible PP1 interactome dataset ever captured from any tissue, including both primary and secondary/tertiary interactors. Nine PP1c interactors with changes in their binding to PP1c were strongly associated with HF progression including two known (Ppp1r7, Ppp1r18) and 7 novel interactors. Within the entire cardiac PP1 interactome, Ppp1r7 had the highest binding to PP1c. Cardiac-specific knockdown in mice led to cardiac dysfunction and disruption of calcium release from the sarcoplasmic reticulum. Conclusions -PP1 is best studied at the level of its interactome, which undergoes significant rearrangement during HF progression. The nine key interactors that are

The human cytoplasmic dynein interactome reveals novel activators of motility

PubMed Central

Redwine, William B; DeSantis, Morgan E; Hollyer, Ian; Htet, Zaw Min; Tran, Phuoc Tien; Swanson, Selene K; Florens, Laurence; Washburn, Michael P; Reck-Peterson, Samara L

2017-01-01

In human cells, cytoplasmic dynein-1 is essential for long-distance transport of many cargos, including organelles, RNAs, proteins, and viruses, towards microtubule minus ends. To understand how a single motor achieves cargo specificity, we identified the human dynein interactome by attaching a promiscuous biotin ligase (‘BioID’) to seven components of the dynein machinery, including a subunit of the essential cofactor dynactin. This method reported spatial information about the large cytosolic dynein/dynactin complex in living cells. To achieve maximal motile activity and to bind its cargos, human dynein/dynactin requires ‘activators’, of which only five have been described. We developed methods to identify new activators in our BioID data, and discovered that ninein and ninein-like are a new family of dynein activators. Analysis of the protein interactomes for six activators, including ninein and ninein-like, suggests that each dynein activator has multiple cargos. DOI: http://dx.doi.org/10.7554/eLife.28257.001 PMID:28718761

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

2014-01-01

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

Impact of Underlying Conditions on Zoster-Related Pain and on Quality of Life Following Zoster

PubMed Central

Bricout, Hélène; Bertrand, Isabelle; Perinetti, Emilia; Franco, Elisabetta; Gabutti, Giovanni; Volpi, Antonio

2017-01-01

Abstract Background: Chronic conditions have been investigated as risk factors for developing zoster, but in patients suffering from zoster, the impact of underlying conditions in zoster-related pain and quality of life (QOL) remains unclear. Methods: We performed a post hoc analysis of a prospective cohort study in immunocompetent zoster patients aged 50 years or older, conducted by general practitioners in Italy between 2009 and 2010. Zoster symptoms, pain intensity and characteristics, and physical and mental health scores were assessed at baseline (zoster diagnosis) and at 1, 3, and 6 months of follow-up. Results: Among 413 patients enrolled in the study, 73% (303/413) suffered from underlying conditions of which 69% (209/303) were aged 65 or older. Cardiovascular diseases (75%), diabetes (24%), and respiratory diseases (17%) were most frequent. One to three months after onset, zoster patients with underlying conditions experienced more intense zoster-related pain than those without. QOL scores were significantly lower in patients with underlying conditions, and age-adjusted difference in QOL scores between the groups increased over time, demonstrating a slower recovery for patients with underlying conditions. Conclusions: In addition to age, the main risk factor of zoster occurrence and severity, the presence of underlying conditions results in more painful and impactful zoster episodes, creating a significant burden for these patients. PMID:27793966

The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta-interactomes Improve Function Predictions.

PubMed

Wuchty, S; Rajagopala, S V; Blazie, S M; Parrish, J R; Khuri, S; Finley, R L; Uetz, P

2017-01-01

The functions of roughly a third of all proteins in Streptococcus pneumoniae , a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions between evolutionarily conserved proteins in other bacteria. We found that such interactions significantly improved our ability to predict a protein's function, allowing us to provide functional predictions for 299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE Identification of protein interactions in bacterial species can help define the individual roles that proteins play in cellular pathways and pathogenesis. Very few protein interactions have been identified for the important human pathogen S. pneumoniae . We used an experimental approach to identify over 2,000 new protein interactions for S. pneumoniae , the most extensive interactome data for this bacterium to date. To predict protein function, we used our interactome data augmented with interactions from other closely related bacteria. The combination of the experimental data and meta-interactome data significantly improved the prediction results, allowing us to assign possible functions to a large number of poorly characterized proteins.

The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta-interactomes Improve Function Predictions

PubMed Central

Rajagopala, S. V.; Blazie, S. M.; Parrish, J. R.; Khuri, S.; Finley, R. L.

2017-01-01

ABSTRACT The functions of roughly a third of all proteins in Streptococcus pneumoniae, a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions between evolutionarily conserved proteins in other bacteria. We found that such interactions significantly improved our ability to predict a protein’s function, allowing us to provide functional predictions for 299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE Identification of protein interactions in bacterial species can help define the individual roles that proteins play in cellular pathways and pathogenesis. Very few protein interactions have been identified for the important human pathogen S. pneumoniae. We used an experimental approach to identify over 2,000 new protein interactions for S. pneumoniae, the most extensive interactome data for this bacterium to date. To predict protein function, we used our interactome data augmented with interactions from other closely related bacteria. The combination of the experimental data and meta-interactome data significantly improved the prediction results, allowing us to assign possible functions to a large number of poorly characterized proteins. PMID:28744484

Vaccination against herpes zoster in developed countries: state of the evidence.

PubMed

Drolet, Mélanie; Oxman, Michael N; Levin, Myron J; Schmader, Kenneth E; Johnson, Robert W; Patrick, David; Mansi, James A; Brisson, Marc

2013-05-01

Although progress has been made in the treatment of herpes zoster (HZ) and postherpetic neuralgia (PHN), available therapeutic options are only partially effective. Given evidence that a live-attenuated varicella-zoster-virus vaccine is effective at reducing the incidence of HZ, PHN and the burden of illness, policymakers and clinicians are being asked to make recommendations regarding the use of the zoster vaccine. In this report, we summarize the evidence regarding the: (1) burden of illness; (2) vaccine efficacy and safety; and (3) cost-effectiveness of vaccination, to assist evidence-based policy making and guide clinicians in their recommendations. First, there is general agreement that the overall burden of illness associated with HZ and PHN is substantial. Second, the safety and efficacy of the zoster vaccine at reducing the burden of illness due to HZ and the incidence of PHN have been clearly demonstrated in large placebo-controlled trials. However, uncertainty remains about the vaccine's duration of protection. Third, vaccination against HZ is likely to be cost-effective when the vaccine is given at approximately 65 y of age, if vaccine duration is longer than 10 y.

Herpes zoster duplex bilateralis in an immunocompetent adolescent boy: a case report and literature review.

PubMed

Yan, Chen; Laguna, Benjamin A; Marlowe, Lauren E; Keller, Michael D; Treat, James R

2014-01-01

Simultaneous involvement of herpes zoster in multiple dermatomes is uncommon, and even more so in immunocompetent individuals. We report a case wherein a healthy adolescent boy presented with herpes zoster in two distinct dermatomes, raising concern for immunodeficiency, but he was found to be immunocompetent on further testing. A 14-year-old boy with no significant past medical history developed painless vesicular eruptions in two distinct distributions. Varicella zoster virus polymerase chain reaction was positive from unroofed vesicles in both regions. Initial laboratory studies disclosed abnormalities of unknown significance in natural killer (NK) cell percentage and function. The patient was treated with appropriate antiviral therapy. Repeat studies while healthy were not suggestive of an underlying NK cell defect. There are few case reports describing herpes zoster in two or more dermatomes in children. Previously described presentations most commonly occurred in the context of primary immunodeficiency, acquired immunodeficiency, or immunosuppressive medications. Because of the rarity of this presentation in immunocompetent patients, the authors recommend a thorough immune evaluation of all children presenting with isolated multidermatomal zoster. © 2014 Wiley Periodicals, Inc.

Real World Evidence for Regulatory Decisions: Concomitant Administration of Zoster Vaccine Live and Pneumococcal Polysaccharide Vaccine.

PubMed

Bruxvoort, Katia; Sy, Lina S; Luo, Yi; Tseng, Hung Fu

2018-04-11

The US Food and Drug Administration is charged with expanding the use of real world evidence (RWE) for regulatory decisions. As a test case for RWE to support regulatory decisions, we present the scenario of concomitant vaccination with zoster vaccine live (ZVL) and 23-valent pneumococcal polysaccharide vaccine (PPSV23). The prescribing information states that these vaccines should not be given concurrently, based on a small trial using varicella zoster virus antibody levels as a correlate of ZVL efficacy, even though ZVL protects against herpes zoster via cell-mediated immunity. We conducted an observational cohort study involving >30,000 members of Kaiser Permanente Southern California receiving concomitant ZVL and PPSV23 versus PPSV23 prior to ZVL. Occurrence of herpes zoster was assessed through electronic health records from January 1, 2007 to June 30, 2016. The adjusted hazard ratio comparing incidence rates of herpes zoster in the concomitant vaccination cohort and the prior vaccination cohort was 1.04 (95% CI: 0.92, 1.16). This RWE study provides direct evidence for a lack of vaccine interference, relying on herpes zoster occurrence rather than an intermediate marker of immunity. RWE is essential for regulators and policy makers in addressing evidentiary gaps regarding safety, effectiveness, compliance, and vaccine interactions for the new recombinant zoster vaccine.

Herpes zoster vaccine in Korea.

PubMed

Choi, Won Suk

2013-07-01

Herpes zoster and post-herpetic neuralgia deteriorate the quality of life because of severe pain and complications, and cause considerable social and economic burden of disease. In 2012, herpes zoster vaccine was released in Korea. The efficacy of herpes zoster vaccine is known to be 51.3-66.5% among the aged over 60 and 69.8-72.4% among adults between 50 and 59. It is also known that preventive efficacy is maintained for at least 5 years. Although there can be local reactions such as redness, pain and swelling at the site of injection and systemic reaction such as headache and eruption after herpes zoster vaccination, most of the adverse reactions are minor and disappear within days by themselves. As it is a live vaccine, persons with severe immune-suppression and pregnant women should not be vaccinated with the vaccine. Currently, Korean Society of Infectious Diseases recommended for the aged over 60 to be vaccinated with herpes zoster vaccine by subcutaneous route. In this article, clinical aspects and burden of disease of herpes zoster, efficacy and effects of herpes zoster vaccine, and herpes zoster vaccine recommendation by Korean Society of Infectious Diseases are discussed.

Herpes zoster vaccine in Korea

PubMed Central

2013-01-01

Herpes zoster and post-herpetic neuralgia deteriorate the quality of life because of severe pain and complications, and cause considerable social and economic burden of disease. In 2012, herpes zoster vaccine was released in Korea. The efficacy of herpes zoster vaccine is known to be 51.3-66.5% among the aged over 60 and 69.8-72.4% among adults between 50 and 59. It is also known that preventive efficacy is maintained for at least 5 years. Although there can be local reactions such as redness, pain and swelling at the site of injection and systemic reaction such as headache and eruption after herpes zoster vaccination, most of the adverse reactions are minor and disappear within days by themselves. As it is a live vaccine, persons with severe immune-suppression and pregnant women should not be vaccinated with the vaccine. Currently, Korean Society of Infectious Diseases recommended for the aged over 60 to be vaccinated with herpes zoster vaccine by subcutaneous route. In this article, clinical aspects and burden of disease of herpes zoster, efficacy and effects of herpes zoster vaccine, and herpes zoster vaccine recommendation by Korean Society of Infectious Diseases are discussed. PMID:23858399

Shingles (Herpes Zoster)

MedlinePlus

... Form Controls Cancel Submit Search The CDC Shingles (Herpes Zoster) Note: Javascript is disabled or is not ... United States will develop shingles, also known as herpes zoster, in their lifetime. There are an estimated ...

Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

2014-01-01

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

Virtual Interactomics of Proteins from Biochemical Standpoint

PubMed Central

Kubrycht, Jaroslav; Sigler, Karel; Souček, Pavel

2012-01-01

Virtual interactomics represents a rapidly developing scientific area on the boundary line of bioinformatics and interactomics. Protein-related virtual interactomics then comprises instrumental tools for prediction, simulation, and networking of the majority of interactions important for structural and individual reproduction, differentiation, recognition, signaling, regulation, and metabolic pathways of cells and organisms. Here, we describe the main areas of virtual protein interactomics, that is, structurally based comparative analysis and prediction of functionally important interacting sites, mimotope-assisted and combined epitope prediction, molecular (protein) docking studies, and investigation of protein interaction networks. Detailed information about some interesting methodological approaches and online accessible programs or databases is displayed in our tables. Considerable part of the text deals with the searches for common conserved or functionally convergent protein regions and subgraphs of conserved interaction networks, new outstanding trends and clinically interesting results. In agreement with the presented data and relationships, virtual interactomic tools improve our scientific knowledge, help us to formulate working hypotheses, and they frequently also mediate variously important in silico simulations. PMID:22928109

Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans

PubMed Central

Messaoudi, Ilhem; Barron, Alexander; Wellish, Mary; Engelmann, Flora; Legasse, Alfred; Planer, Shannon; Gilden, Don; Nikolich-Zugich, Janko; Mahalingam, Ravi

2009-01-01

Simian varicella virus (SVV), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV). Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP) resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox) in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation. PMID:19911054

Simian varicella virus infection of rhesus macaques recapitulates essential features of varicella zoster virus infection in humans.

PubMed

Messaoudi, Ilhem; Barron, Alexander; Wellish, Mary; Engelmann, Flora; Legasse, Alfred; Planer, Shannon; Gilden, Don; Nikolich-Zugich, Janko; Mahalingam, Ravi

2009-11-01

Simian varicella virus (SVV), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV). Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP) resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox) in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation.

The interactome of CCT complex - A computational analysis.

PubMed

Narayanan, Aswathy; Pullepu, Dileep; Kabir, M Anaul

2016-10-01

The eukaryotic chaperonin, CCT (Chaperonin Containing TCP1 or TriC-TCP-1 Ring Complex) has been subjected to physical and genetic analyses in S. cerevisiae which can be extrapolated to human CCT (hCCT), owing to its structural and functional similarities with yeast CCT (yCCT). Studies on hCCT and its interactome acquire an additional dimension, as it has been implicated in several disease conditions like neurodegeneration and cancer. We attempt to study its stress response role in general, which will be reflected in the aspects of human diseases and yeast physiology, through computational analysis of the interactome. Towards consolidating and analysing the interactome data, we prepared and compared the unique CCT-interacting protein lists for S. cerevisiae and H. sapiens, performed GO term classification and enrichment studies which provide information on the diversity in CCT interactome, in terms of protein classes in the data set. Enrichment with disease-associated proteins and pathways highlight the medical importance of CCT. Different analyses converge, suggesting the significance of WD-repeat proteins, protein kinases and cytoskeletal proteins in the interactome. The prevalence of proteasomal subunits and ribosomal proteins suggest a possible cross-talk between protein-synthesis, folding and degradation machinery. A network of chaperones and chaperonins that function in combination can also be envisaged from the CCT interactome-Hsp70 interactome analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Varicella zoster virus myelitis in two elderly patients: diagnostic value of nested polymerase chain reaction assay and antibody index for cerebrospinal fluid specimens.

PubMed

Takahashi, Teruyuki; Tamura, Masato; Miki, Kenji; Yamaguchi, Mai; Kanno, Akira; Nunomura, Satoshi; Ra, Chisei; Tamiya, Takashi; Kamei, Satoshi; Takasu, Toshiaki

2013-01-01

Myelitis is one of the rarest neurological complications of the varicella zoster virus (VZV) infection. Focal muscle weakness with or without sensory disturbance occurs in approximately 5% of the cases after acute VZV infection, with complete recovery in 50-70%. This report describes two rare cases of elderly patients with VZV myelitis secondary to dermatomal zoster rash. Patient 1 was a 79-year-old woman who developed paraplegia, numbness and decreased sensation in the left arm and below thoracic (Th)-10 after sacral zoster. Spinal cord MRI showed a high-signal-intensity lesion at the cervical spinal nerve 2 on a T2-weighted image. Patient 2 was a 73-year-old man who developed right flaccid leg weakness and urinary retention after right dorsal Th 5-8 zoster. Spinal cord MRI showed a high-signal-intensity lesion at Th 3-4 on a T2-weighted image. In both cases, although the conventional single polymerase chain reaction (PCR) assays all showed negative results, the original nested PCR assay detected VZV DNA in the cerebrospinal fluid (CSF) specimen collected on admission. In addition, the anti-VZV IgG antibody by enzyme immunoassay and antibody index were elevated in the CSF specimens during the clinical courses of both patients. On the basis of these findings, both patients were diagnosed with VZV myelitis and were treated with high-dose acyclovir and corticosteroid. This combined treatment was appropriate and effective for the improvement of their functional outcomes. The detection of VZV DNA in CSF by nested PCR assay and the evaluation of the antibody index to VZV had significant diagnostic value.

Photocrosslinking approaches to interactome mapping

PubMed Central

Pham, Nam D.; Parker, Randy B.; Kohler, Jennifer J.

2012-01-01

Photocrosslinking approaches can be used to map interactome networks within the context of living cells. Photocrosslinking methods rely on use of metabolic engineering or genetic code expansion to incorporate photocrosslinking analogs of amino acids or sugars into cellular biomolecules. Immunological and mass spectrometry techniques are used to analyze crosslinked complexes, thereby defining specific interactomes. Because photocrosslinking can be conducted in native, cellular settings, it can be used to define context-dependent interactions. Photocrosslinking methods are also ideally suited for determining interactome dynamics, mapping interaction interfaces, and identifying transient interactions in which intrinsically disordered proteins and glycoproteins engage. Here we discuss the application of cell-based photocrosslinking to the study of specific problems in immune cell signaling, transcription, membrane protein dynamics, nucleocytoplasmic transport, and chaperone-assisted protein folding. PMID:23149092

Interactome disassembly during apoptosis occurs independent of caspase cleavage.

PubMed

Scott, Nichollas E; Rogers, Lindsay D; Prudova, Anna; Brown, Nat F; Fortelny, Nikolaus; Overall, Christopher M; Foster, Leonard J

2017-01-12

Protein-protein interaction networks (interactomes) define the functionality of all biological systems. In apoptosis, proteolysis by caspases is thought to initiate disassembly of protein complexes and cell death. Here we used a quantitative proteomics approach, protein correlation profiling (PCP), to explore changes in cytoplasmic and mitochondrial interactomes in response to apoptosis initiation as a function of caspase activity. We measured the response to initiation of Fas-mediated apoptosis in 17,991 interactions among 2,779 proteins, comprising the largest dynamic interactome to date. The majority of interactions were unaffected early in apoptosis, but multiple complexes containing known caspase targets were disassembled. Nonetheless, proteome-wide analysis of proteolytic processing by terminal amine isotopic labeling of substrates (TAILS) revealed little correlation between proteolytic and interactome changes. Our findings show that, in apoptosis, significant interactome alterations occur before and independently of caspase activity. Thus, apoptosis initiation includes a tight program of interactome rearrangement, leading to disassembly of relatively few, select complexes. These early interactome alterations occur independently of cleavage of these protein by caspases. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

[Modelling the impact of vaccination on the epidemiology of varicella zoster virus].

PubMed

Bonmarin, I; Santa-Olalla, P; Lévy-Bruhl, D

2008-10-01

The soon to come the availability of a combined MMR-varicella vaccine has re-stimulated the debate around universal infant vaccination against varicella. In France, the incidence of varicella is estimated at about 700,000 cases per year, with approximately 3500 hospitalisations and 15-25 deaths, the latter mainly occurring in those over 15years. Vaccination would certainly decrease the overall incidence of the disease but concerns about vaccination leading to a shift in the average age at infection followed by an increase in incidence of severe cases and congenital varicella, still remain. In order to provide support for decision-making, a dynamic mathematical model of varicella virus transmission was used to predict the effect of different vaccination strategies and coverages on the epidemiology of varicella and zoster. A deterministic realistic age-structured model was adapted to the French situation. Epidemiological parameters were estimated from literature or surveillance data. Various vaccine coverages and vaccination strategies were investigated. A sensitivity analysis of varicella incidence predictions was performed to test the impact of changes in the vaccine parameters and age-specific mixing patterns. The model confirms that the overall incidence and morbidity of varicella would likely be reduced by mass vaccination of 12-month-old children. Whatever the coverage and the vaccine strategy, the vaccination will cause a shift in age distribution with, for vaccination coverage up to at least 80% in the base-case analysis, an increased morbidity among adults and pregnant women. However, the total number of deaths and hospitalisations from varicella is predicted to remain below that expected without vaccination. The model is very sensitive to the matrix of contacts used and to the parameters describing vaccine effectiveness. Zoster incidence will increase over a number of decades followed by a decline to below prevaccination levels. Mass varicella vaccination

Incidence and case-fatality of varicella-zoster virus infection among pediatric cancer patients in developing countries.

PubMed

Ojha, Rohit P; Stallings-Smith, Sericea; Aviles-Robles, Martha J; Gomez, Sergio; Somarriba, María Mercedes; Caniza, Miguela A

2016-04-01

Limited evidence is available about varicella-zoster virus (VZV) infection among pediatric cancer patients in developing countries, which raises questions about the generalizability of VZV vaccine recommendations for pediatric cancer patients (derived from developed countries) to these settings. We assessed the incidence and case-fatality of VZV infection at three institutions in developing countries (Argentina, Mexico, and Nicaragua). Individuals eligible for our study were aged <20 years and actively receiving cancer-directed therapy. We estimated a summary incidence rate (IR) and case-fatality risk with corresponding 95 % confidence limits (CL) of VZV infection across sites using random-effects models. Our study population comprised 511 pediatric cancer patients, of whom 64 % were aged <10 years, 58 % were male, and 58 % were diagnosed with leukemia. We observed a total of 10 infections during 44,401 person-days of follow-up across the 3 sites (IR = 2.3, 95 % CL 1.2, 4.2). The summary case-fatality risk was 10 % (95 % CL 1.4, 47 %) based on one death. Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. VZV vaccine recommendations for pediatric cancer patients in developed countries may be generalizable to developing countries. • Current recommendations, based on evidence from pediatric cancer patients in developed countries, contraindicate varicella-zoster virus (VZV) vaccination until completion of cancer-directed therapy and recovery of immune function. • The generalizability of these VZV vaccine recommendations to pediatric cancer patients in developing countries is unknown because of limited information about the incidence and case-fatality of VZV in these settings. What is New: • Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. • VZV vaccine recommendations based on evidence from

Use of lambdagt11 to isolate genes for two pseudorabies virus glycoproteins with homology to herpes simplex virus and varicella-zoster virus glycoproteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petrovskis, E.A.; Timmins, J.G.; Post, L.E.

1986-10-01

A library of pseudorabies virus (PRV) DNA fragments was constructed in the expression cloning vector lambdagt11. The library was screened with antisera which reacted with mixtures of PRV proteins to isolate recombinant bacteriophages expressing PRV proteins. By the nature of the lambdagt11 vector, the cloned proteins were expressed in Escherichia coli as ..beta..-galactosidase fusion proteins. The fusion proteins from 35 of these phages were purified and injected into mice to raise antisera. The antisera were screened by several different assays, including immunoprecipitation of (/sup 14/C)glucosamine-labeled PRV proteins. This method identified phages expressing three different PRV glycoproteins: the secreted glycoprotein, gX;more » gI; and a glycoprotein that had not been previously identified, which we designate gp63. The gp63 and gI genes map adjacent to each other in the small unique region of the PRV genome. The DNA sequence was determined for the region of the genome encoding gp63 and gI. It was found that gp63 has a region of homology with a herpes simplex virus type 1 (HSV-1) protein, encoded by US7, and also with varicella-zoster virus (VZV) gpIV. The gI protein sequence has a region of homology with HSV-1 gE and VZV gpI. It is concluded that PRV, HSV, and VZV all have a cluster of homologous glycoprotein genes in the small unique components of their genomes and that the organization of these genes is conserved.« less

Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management.

PubMed

Arvin, Ann M; Wolinsky, Jerry S; Kappos, Ludwig; Morris, Michele I; Reder, Anthony T; Tornatore, Carlo; Gershon, Anne; Gershon, Michael; Levin, Myron J; Bezuidenhoudt, Mauritz; Putzki, Norman

2015-01-01

Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity. To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management. Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated. In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54,000 patient-years at the time of analysis). Calculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting. Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical

Childhood varicella-zoster virus vaccination in Belgium: cost-effective only in the long run or without exogenous boosting?

PubMed

Bilcke, Joke; van Hoek, Albert Jan; Beutels, Philippe

2013-04-01

To assess the effectiveness and cost-effectiveness of a universal childhood varicella-zoster vaccination programme in Belgium (1) using the most recent Belgian data on varicella-zoster burden, (2) exploring different options for the timing of the second dose, (3) obtaining results with and without exogenous natural boosting, and (4) investigating the possible additional benefit of zoster booster vaccination for adults at age 50 or 60 y. An extensively studied and improved dynamic model is used to estimate primary and breakthrough chickenpox and zoster cases over time. For a range of vaccination options, we compared the direct costs (health care payer perspective) and health outcomes (including Quality-Adjusted Life-Years (QALYs) lost) associated with chickenpox and herpes zoster. Estimates of social contact patterns, health care use, costs and QALY losses are almost exclusively based on Belgian databases and surveys. If exogenous natural boosting exists, a net loss in QALYs is expected for several decades after implementing a universal chickenpox vaccination programme, due to an increase in zoster mainly in persons aged 50-80 y. This result holds also for scenarios that minimise or counteract the expected increase in zoster incidence (e.g. additional booster vaccinations in adults). However, if the boosting hypothesis is not true or if costs and QALYs are cumulated over at least 33 to more than 100 y after vaccination (depending on the assumptions made), different options for universal 2-dose vaccination against chickenpox in Belgium would be cost-effective at a vaccine price of €43/dose or lower.

APID interactomes: providing proteome-based interactomes with controlled quality for multiple species and derived networks

PubMed Central

Alonso-López, Diego; Gutiérrez, Miguel A.; Lopes, Katia P.; Prieto, Carlos; Santamaría, Rodrigo; De Las Rivas, Javier

2016-01-01

APID (Agile Protein Interactomes DataServer) is an interactive web server that provides unified generation and delivery of protein interactomes mapped to their respective proteomes. This resource is a new, fully redesigned server that includes a comprehensive collection of protein interactomes for more than 400 organisms (25 of which include more than 500 interactions) produced by the integration of only experimentally validated protein–protein physical interactions. For each protein–protein interaction (PPI) the server includes currently reported information about its experimental validation to allow selection and filtering at different quality levels. As a whole, it provides easy access to the interactomes from specific species and includes a global uniform compendium of 90,379 distinct proteins and 678,441 singular interactions. APID integrates and unifies PPIs from major primary databases of molecular interactions, from other specific repositories and also from experimentally resolved 3D structures of protein complexes where more than two proteins were identified. For this purpose, a collection of 8,388 structures were analyzed to identify specific PPIs. APID also includes a new graph tool (based on Cytoscape.js) for visualization and interactive analyses of PPI networks. The server does not require registration and it is freely available for use at http://apid.dep.usal.es. PMID:27131791

Evolution of Cocirculating Varicella-Zoster Virus Genotypes during a Chickenpox Outbreak in Guinea-Bissau

PubMed Central

Gray, Eleanor R.; Kundu, Samit; Cooray, Samantha; Poulsen, Anja; Aaby, Peter; Breuer, Judith

2014-01-01

ABSTRACT Varicella-zoster virus (VZV), a double-stranded DNA alphaherpesvirus, is associated with seasonal outbreaks of varicella in nonimmunized populations. Little is known about whether these outbreaks are associated with a single or multiple viral genotypes and whether new mutations rapidly accumulate during transmission. Here, we take advantage of a well-characterized population cohort in Guinea-Bissau and produce a unique set of 23 full-length genome sequences, collected over 7 months from eight households. Comparative sequence analysis reveals that four distinct genotypes cocirculated among the population, three of which were present during the first week of the outbreak, although no patients were coinfected, which indicates that exposure to infectious virus from multiple sources is common during VZV outbreaks. Transmission of VZV was associated with length polymorphisms in the R1 repeat region and the origin of DNA replication. In two cases, these were associated with the formation of distinct lineages and point to the possible coevolution of these loci, despite the lack of any known functional link in VZV or related herpesviruses. We show that these and all other sequenced clade 5 viruses possess a distinct R1 repeat motif that increases the acidity of an ORF11p protein domain and postulate that this has either arisen or been lost following divergence of the major clades. Thus, sequencing of whole VZV genomes collected during an outbreak has provided novel insights into VZV biology, transmission patterns, and (recent) natural history. IMPORTANCE VZV is a highly infectious virus and the causative agent of chickenpox and shingles, the latter being particularly associated with the risk of painful complications. Seasonal outbreaks of chickenpox are very common among young children, yet little is known about the dynamics of the virus during person-to-person to transmission or whether multiple distinct viruses seed and/or cocirculate during an outbreak. In this

Evolution of cocirculating varicella-zoster virus genotypes during a chickenpox outbreak in Guinea-Bissau.

PubMed

Depledge, Daniel P; Gray, Eleanor R; Kundu, Samit; Cooray, Samantha; Poulsen, Anja; Aaby, Peter; Breuer, Judith

2014-12-01

Varicella-zoster virus (VZV), a double-stranded DNA alphaherpesvirus, is associated with seasonal outbreaks of varicella in nonimmunized populations. Little is known about whether these outbreaks are associated with a single or multiple viral genotypes and whether new mutations rapidly accumulate during transmission. Here, we take advantage of a well-characterized population cohort in Guinea-Bissau and produce a unique set of 23 full-length genome sequences, collected over 7 months from eight households. Comparative sequence analysis reveals that four distinct genotypes cocirculated among the population, three of which were present during the first week of the outbreak, although no patients were coinfected, which indicates that exposure to infectious virus from multiple sources is common during VZV outbreaks. Transmission of VZV was associated with length polymorphisms in the R1 repeat region and the origin of DNA replication. In two cases, these were associated with the formation of distinct lineages and point to the possible coevolution of these loci, despite the lack of any known functional link in VZV or related herpesviruses. We show that these and all other sequenced clade 5 viruses possess a distinct R1 repeat motif that increases the acidity of an ORF11p protein domain and postulate that this has either arisen or been lost following divergence of the major clades. Thus, sequencing of whole VZV genomes collected during an outbreak has provided novel insights into VZV biology, transmission patterns, and (recent) natural history. VZV is a highly infectious virus and the causative agent of chickenpox and shingles, the latter being particularly associated with the risk of painful complications. Seasonal outbreaks of chickenpox are very common among young children, yet little is known about the dynamics of the virus during person-to-person to transmission or whether multiple distinct viruses seed and/or cocirculate during an outbreak. In this study, we have

Clinical Herpes Zoster in Antarctica as a Model for Spaceflight.

PubMed

Reyes, David P; Brinley, Alaina A; Blue, Rebecca S; Gruschkus, Stephen K; Allen, Andrew T; Parazynski, Scott E

2017-08-01

Antarctica is a useful analog for spaceflight, as both environments are remote, isolated, and with limited resources. While previous studies have demonstrated increased asymptomatic viral shedding in both the Antarctic and spaceflight environments, clinical manifestations of reactivated viral disease have been less frequently identified. We sought to identify the incidence of clinical herpes zoster from viral reactivation in the Antarctic winter-over population. Medical records from the 2014 winter season were reviewed for the incidence of zoster in U.S. Antarctic personnel and then compared to the age-matched U.S. Five cases of clinical herpes zoster occurred in the Antarctic Station population of 204 persons, for an incidence of 33.3 per 1000 person-years vs. 3.2 per 1000 person-years in the general population. Four cases were in persons under age 40, yielding an incidence of 106.7 per 1000 person-years in persons ages 30-39 compared to an incidence of 2.0 per 1000 person-years in the same U.S. age group. Immune suppression due to the stressful Antarctic environment may have contributed to the increased incidence of herpes zoster in U.S. Antarctic personnel during the winter of 2014. Working and living in isolated, confined, and extreme environments can cause immune suppression, reactivating latent viruses and increasing viral shedding and symptomatic disease. Such changes have been observed in other austere environments, including spaceflight, suggesting that clinical manifestations of viral reactivation may be seen in future spaceflight.Reyes DP, Brinley AA, Blue RS, Gruschkus SK, Allen AT, Parazynski SE. Clinical herpes zoster in Antarctica as a model for spaceflight. Aerosp Med Hum Perform. 2017; 88(8):784-788.

HIV–host interactome revealed directly from infected cells

PubMed Central

Luo, Yang; Jacobs, Erica Y.; Greco, Todd M.; Mohammed, Kevin D.; Tong, Tommy; Keegan, Sarah; Binley, James M.; Cristea, Ileana M.; Fenyö, David; Rout, Michael P.; Chait, Brian T.; Muesing, Mark A.

2016-01-01

Although genetically compact, HIV-1 commandeers vast arrays of cellular machinery to sustain and protect it during cycles of viral outgrowth. Transposon-mediated saturation linker scanning mutagenesis was used to isolate fully replication-competent viruses harbouring a potent foreign epitope tag. Using these viral isolates, we performed differential isotopic labelling and affinity-capture mass spectrometric analyses on samples obtained from cultures of human lymphocytes to classify the vicinal interactomes of the viral Env and Vif proteins as they occur during natural infection. Importantly, interacting proteins were recovered without bias, regardless of their potential for positive, negative or neutral impact on viral replication. We identified specific host associations made with trimerized Env during its biosynthesis, at virological synapses, with innate immune effectors (such as HLA-E) and with certain cellular signalling pathways (for example, Notch1). We also defined Vif associations with host proteins involved in the control of nuclear transcription and nucleoside biosynthesis as well as those interacting stably or transiently with the cytoplasmic protein degradation apparatus. Our approach is broadly applicable to elucidating pathogen–host interactomes, providing high-certainty identification of interactors by their direct access during cycling infection. Understanding the pathophysiological consequences of these associations is likely to provide strategic targets for antiviral intervention. PMID:27375898

Herpes zoster following cryosurgery.

PubMed

Lee, Michael R; Ryman, William

2005-02-01

A 56-year-old man developed reactivation of herpes zoster infection on his right forehead after treatment of several solar keratoses with cryosurgery. The rash was blistering and painful. Treatment with oral aciclovir was instituted and the lesions healed within 2 weeks. Known risk factors for reactivation include age and decreased immunity. Previous case reports have indicated trauma may be a risk factor in herpes zoster. We report a case of herpes zoster as a complication of cryosurgery.

Selection and Characterization of Drug-Resistant Variants of Human Immunodeficiency Virus (AIDS).

DTIC Science & Technology

1995-10-01

on Antiviral Reserach, Santa Fe, New Mexico , 1995. Page 18 APPENDIX Page 19 p - FACTFILE Mutations in HIV-1 Reverse Transcriptase and Protease...including herpes simplex viruses, varicella -zoster Resistance of clinical HIV-1 isolates to foscarnet has not virus, cytomegalovirus (CMV), hepatitis B...This effect of the Tyr-208 substitution was not ob- reported previously for herpes simplex viruses, varicella -zoster served in MT-2 cells, however. virus

Clinical features of viral meningitis in adults: significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections.

PubMed

Ihekwaba, Ugo K; Kudesia, Goura; McKendrick, Michael W

2008-09-15

In this retrospective study, our objective was to review the epidemiology of viral meningitis and to compare clinical features associated with enterovirus, herpes simplex virus (HSV), and varicella zoster virus (VZV) infections in immunocompetent adults. Data on cerebrospinal fluid (CSF) samples submitted to the Trust Virology Laboratory (Sheffield, UK) from April 2004 through April 2007 were reviewed. Notes on immunocompetent adults who were polymerase chain reaction (PCR) positive for enterovirus, HSV type 2, or VZV and who had presented to local clinical departments were scrutinized (4 patients were positive for HSV type 1 and did not meet the inclusion criteria). A total of 2045 samples were analyzed for viral pathogens during the 3-year period. Of the 109 PCR-positive samples, 38 (35%) were from immunocompetent adults, of whom 22 were infected with enterovirus, 8 were infected with HSV type 2, and 8 were infected with VZV. The median ages were 32 years (range, 16-39 years), 39 years (range, 22-53 years), and 47.5 years (range, 26-80 years), respectively. Rash occurred after the meningitis symptoms in 5 patients infected with VZV (median time from meningitis symptoms to rash, 6 days). Protein levels were significantly higher in CSF samples from patients infected with HSV type 2 (median, 1205 mg/L) and in samples from those infected with VZV (median, 974 mg/L) than in samples from those infected with enterovirus (median, 640 mg/L; P = .001 and P = .01, respectively). White blood cell counts were significantly higher in CSF samples from patients infected with HSV type 2 (median, 240 x 10(6) cells/L) than in samples from those infected with enterovirus (median, 51 x 10(6) cells/L; P = .01). Enterovirus infection was the most common cause of viral meningitis in immunocompetent adults in this study. White blood cell counts and protein levels were significantly higher in CSF samples from patients infected with HSV type 2 than in samples from patients with enterovirus

Disease burden of herpes zoster in Sweden - predominance in the elderly and in women - a register based study

PubMed Central

2013-01-01

Background The herpes zoster burden of disease in Sweden is not well investigated. There is no Swedish immunization program to prevent varicella zoster virus infections. A vaccine against herpes zoster and its complications is now available. The aim of this study was to estimate the herpes zoster burden of disease and to establish a pre-vaccination baseline of the minimum incidence of herpes zoster. Methods Data were collected from the Swedish National Health Data Registers including the Patient Register, the Pharmacy Register, and the Cause of Death Register. The herpes zoster burden of disease in Sweden was estimated by analyzing the overall, and age and gender differences in the antiviral prescriptions, hospitalizations and complications during 2006-2010 and mortality during 2006-2009. Results Annually, 270 per 100,000 persons received antiviral treatment for herpes zoster, and the prescription rate increased with age. It was approximately 50% higher in females than in males in the age 50+ population (rate ratio 1.39; 95% CI, 1.22 to 1.58). The overall hospitalization rate for herpes zoster was 6.9/100,000 with an approximately three-fold increase for patients over 80 years of age compared to the age 70-79 group. A gender difference in hospitalization rates was observed: 8.1/100,000 in females and 5.6/100,000 in males. Herpes zoster, with a registered complication, was found in about one third of the hospitalized patients and the most common complications involved the peripheral and central nervous systems. Death due to herpes zoster was a rare event. Conclusions The results of this study demonstrate the significant burden of herpes zoster disease in the pre-zoster vaccination era. A strong correlation with age in the herpes zoster- related incidence, hospitalization, complications, and mortality rates was found. In addition, the study provides further evidence of the female predominance in herpes zoster disease. PMID:24330510

Shingles (Herpes Zoster) Vaccine (Zostavax(®)): A Review in the Prevention of Herpes Zoster and Postherpetic Neuralgia.

PubMed

Keating, Gillian M

2016-06-01

Zostavax(®) is a live attenuated shingles (herpes zoster) vaccine approved in the EU for the prevention of herpes zoster (HZ) and postherpetic neuralgia (PHN) in adults aged ≥50 years. Zoster vaccine protected against HZ in adults aged 50-59 years (ZEST trial) and ≥60 years [Shingles Prevention Study (SPS)], and also reduced the burden of illness associated with HZ and the risk of PHN in adults aged ≥60 years (SPS). A large amount of real-world data also supports the efficacy of zoster vaccine. Results of the SPS Short- and Long-Term Persistence Substudies and real-world studies indicate that zoster vaccine provided continued benefit in the longer term, albeit with a gradual decline in vaccine efficacy over time; long-term effectiveness studies are ongoing. The need for a booster dose is still unknown, but a study showed that, if necessary, a booster dose administered to adults aged ≥70 years who received their first dose of zoster vaccine ≥10 years previously was immunogenic. Zoster vaccine had a favourable safety and tolerability profile, with the most commonly reported adverse events being non-severe injection-site reactions. In conclusion, zoster vaccine reduces the incidence of HZ and PHN, thereby reducing the burden of illness associated with HZ; improved uptake of zoster vaccine is needed.

Longitudinal Study on Oral Shedding of Herpes Simplex Virus 1 and Varicella-Zoster Virus in Individuals Infected with HIV

PubMed Central

van Velzen, Monique; Ouwendijk, Werner J.D.; Selke, Stacy; Pas, Suzan D.; van Loenen, Freek B.; Osterhaus, Albert D.M.E.; Wald, Anna; Verjans, Georges M.G.M.

2014-01-01

Primary herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) infection leads to a life-long latent infection of ganglia innervating the oral mucosa. HSV-1 and VZV reactivation is more common in immunocompromised individuals and may result in viral shedding in saliva. We determined the kinetics and quantity of oral HSV-1 and VZV shedding in HSV-1 and VZV seropositive individuals infected with HIV and to assess whether HSV-1 shedding involves reactivation of the same strain intra-individually. HSV-1 and VZV shedding was determined by real-time PCR of sequential daily oral swabs (n=715) collected for a median period of 31 days from 22 individuals infected with HIV. HSV-1 was genotyped by sequencing the viral thymidine kinase gene. Herpesvirus shedding was detected in 18 of 22 participants. Shedding of HSV-1 occurred frequently, on 14.3% of days, whereas solely VZV shedding was very rare. Two participants shed VZV. The median HSV-1 load was higher compared to VZV. HSV-1 DNA positive swabs clustered into 34 shedding episodes with a median duration of 2 days. The prevalence, duration and viral load of herpesvirus shedding did not correlate with CD4 counts and HIV load. The genotypes of the HSV-1 viruses shed were identical between and within shedding episodes of the same person, but were different between individuals. One-third of the individuals shed an HSV-1 strain potentially refractory to acyclovir therapy. Compared to HSV-1, oral VZV shedding is rare in individuals infected with HIV. Recurrent oral HSV-1 shedding is likely due to reactivation of the same latent HSV-1 strain. PMID:23780621

Global Identification of Three Major Genotypes of Varicella-Zoster Virus: Longitudinal Clustering and Strategies for Genotyping

PubMed Central

Loparev, Vladimir N.; Gonzalez, Antonio; Deleon-Carnes, Marlene; Tipples, Graham; Fickenscher, Helmut; Torfason, Einar G.; Schmid, D. Scott

2004-01-01

By analysis of a single, variable, and short DNA sequence of 447 bp located within open reading frame 22 (ORF22), we discriminated three major varicella-zoster virus (VZV) genotypes. VZV isolates from all six inhabited continents that showed nearly complete homology to ORF22 of the European reference strain Dumas were assigned to the European (E) genotype. All Japanese isolates, defined as the Japanese (J) genotype, were identical in the respective genomic region and proved the most divergent from the E strains, carrying four distinct variations. The remaining isolates carried a combination of E- and J-specific variations in the target sequence and thus were collectively termed the mosaic (M) genotype. Three hundred twenty-six isolates collected in 27 countries were genotyped. A distinctive longitudinal distribution of VZV genotypes supports this approach. Among 111 isolates collected from European patients, 96.4% were genotype E. Consistent with this observation, approximately 80% of the VZV strains from the United States were also genotype E. Similarly, genotype E viruses were dominant in the Asian part of Russia and in eastern Australia. M genotype viruses were strongly dominant in tropical regions of Africa, Indochina, and Central America, and they were common in western Australia. However, genotype M viruses were also identified as a minority in several countries worldwide. Two major intertypic variations of genotype M strains were identified, suggesting that the M genotype can be further differentiated into subgenotypes. These data highlight the direction for future VZV genotyping efforts. This approach provides the first simple genotyping method for VZV strains in clinical samples. PMID:15254207

Functional integrative levels in the human interactome recapitulate organ organization.

PubMed

Souiai, Ouissem; Becker, Emmanuelle; Prieto, Carlos; Benkahla, Alia; De las Rivas, Javier; Brun, Christine

2011-01-01

Interactome networks represent sets of possible physical interactions between proteins. They lack spatio-temporal information by construction. However, the specialized functions of the differentiated cell types which are assembled into tissues or organs depend on the combinatorial arrangements of proteins and their physical interactions. Is tissue-specificity, therefore, encoded within the interactome? In order to address this question, we combined protein-protein interactions, expression data, functional annotations and interactome topology. We first identified a subnetwork formed exclusively of proteins whose interactions were observed in all tested tissues. These are mainly involved in housekeeping functions and are located at the topological center of the interactome. This 'Largest Common Interactome Network' represents a 'functional interactome core'. Interestingly, two types of tissue-specific interactions are distinguished when considering function and network topology: tissue-specific interactions involved in regulatory and developmental functions are central whereas tissue-specific interactions involved in organ physiological functions are peripheral. Overall, the functional organization of the human interactome reflects several integrative levels of functions with housekeeping and regulatory tissue-specific functions at the center and physiological tissue-specific functions at the periphery. This gradient of functions recapitulates the organization of organs, from cells to organs. Given that several gradients have already been identified across interactomes, we propose that gradients may represent a general principle of protein-protein interaction network organization.

Functional Integrative Levels in the Human Interactome Recapitulate Organ Organization

PubMed Central

Prieto, Carlos; Benkahla, Alia; De Las Rivas, Javier; Brun, Christine

2011-01-01

Interactome networks represent sets of possible physical interactions between proteins. They lack spatio-temporal information by construction. However, the specialized functions of the differentiated cell types which are assembled into tissues or organs depend on the combinatorial arrangements of proteins and their physical interactions. Is tissue-specificity, therefore, encoded within the interactome? In order to address this question, we combined protein-protein interactions, expression data, functional annotations and interactome topology. We first identified a subnetwork formed exclusively of proteins whose interactions were observed in all tested tissues. These are mainly involved in housekeeping functions and are located at the topological center of the interactome. This ‘Largest Common Interactome Network’ represents a ‘functional interactome core’. Interestingly, two types of tissue-specific interactions are distinguished when considering function and network topology: tissue-specific interactions involved in regulatory and developmental functions are central whereas tissue-specific interactions involved in organ physiological functions are peripheral. Overall, the functional organization of the human interactome reflects several integrative levels of functions with housekeeping and regulatory tissue-specific functions at the center and physiological tissue-specific functions at the periphery. This gradient of functions recapitulates the organization of organs, from cells to organs. Given that several gradients have already been identified across interactomes, we propose that gradients may represent a general principle of protein-protein interaction network organization. PMID:21799769

Management of varicella zoster virus retinitis in AIDS

PubMed Central

Moorthy, R.; Weinberg, D.; Teich, S.; Berger, B.; Minturn, J.; Kumar, S.; Rao, N.; Fowell, S.; Loose, I.; Jampol, L.

1997-01-01

AIMS/BACKGROUND—Varicella zoster virus retinitis (VZVR) in patients with AIDS, also called progressive outer retinal necrosis (PORN), is a necrotising viral retinitis which has resulted in blindness in most patients. The purposes of this study were to investigate the clinical course and visual outcome, and to determine if the choice of a systemic antiviral therapy affected the final visual outcome in patients with VZVR and AIDS.
METHODS—A review of the clinical records of 20 patients with VZVR from six centres was performed. Analysis of the clinical characteristics at presentation was performed. Kruskall-Wallis non-parametric one way analysis of variance (KWAOV) of the final visual acuities of patients treated with acyclovir, ganciclovir, foscarnet, or a combination of foscarnet and ganciclovir was carried out.
RESULTS—Median follow up was 6 months (range 1.3-26 months). On presentation, 14 of 20 patients (70%) had bilateral disease, and 75% (15 of 20 patients) had previous or concurrent extraocular manifestations of VZV infection. Median initial and final visual acuities were 20/40 and hand movements, respectively. Of 39 eyes involved, 19 eyes (49%) were no light perception at last follow up; 27 eyes (69%) developed rhegmatogenous retinal detachments. Patients treated with combination ganciclovir and foscarnet therapy or ganciclovir alone had significantly better final visual acuity than those treated with either acyclovir or foscarnet (KWAOV: p = 0.0051).
CONCLUSIONS—This study represents the second largest series, the longest follow up, and the first analysis of visual outcomes based on medical therapy for AIDS patients with VZVR. Aggressive medical treatment with appropriate systemic antivirals may improve long term visual outcome in patients with VZVR. Acyclovir appears to be relatively ineffective in treating this disease.

 PMID:9135381

The prevention and management of herpes zoster.

PubMed

Cunningham, Anthony L; Breuer, Judith; Dwyer, Dominic E; Gronow, David W; Helme, Robert D; Litt, John C; Levin, Myron J; Macintyre, C Raina

2008-02-04

The burden of illness from herpes zoster (HZ) and postherpetic neuralgia (PHN) in the Australian community is high. The incidence and severity of HZ and PHN increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). Antiviral medications (valaciclovir, famciclovir, aciclovir) have been shown to be effective in reducing much but not all of the morbidity associated with HZ and PHN, but are consistently underprescribed in Australia. Zoster-associated pain should be treated early and aggressively, as it is more difficult to treat once established. Clinicians should be proactive in their follow-up of individuals at high risk of developing PHN, and refer patients to a specialist pain clinic earlier, rather than later. A live, attenuated VZV vaccine (Oka/Merck strain, Zostavax [Merck Sharp & Dohme]) has proven to be efficacious in reducing the incidence of and morbidity associated with HZ and PHN in older adults. The vaccine's efficacy has been shown to persist for at least 4 years, but is likely to last a lot longer. Ongoing surveillance will determine the duration of protection and whether a booster dose is required. Clinicians should consider recommending the vaccine, which can be safely administered at the same time as the inactivated influenza vaccine, to all immunocompetent patients aged 60 years or older. Clinicians should refer to the Australian immunisation handbook for advice on the use of the live vaccine in immunosuppressed individuals.

Human varicella zoster virus is not present in the semen of a man affected by chickenpox during the in vitro fertilisation of his wife.

PubMed

Chan, D Y L; Lam, K K W; Lau, E Y L; Yeung, W S B; Ng, E H Y

2017-12-01

Human varicella zoster virus (VZV) is a member of the herpes virus family and affects humans only. Information about the presence of the virus in the semen samples of men affected by chickenpox is rather limited in the literature. Here, we reported a husband was affected by VZV during in vitro fertilisation treatment of his wife treated in our centre. The semen sample was checked for the presence of VZV by the PCR technique. The PCR result found no detectable viral DNA in the semen sample. The semen sample was then used for conventional IVF insemination and subsequently a healthy baby boy was born. This single case report suggests that the semen sample of men affected by chickenpox may be safe to use for assisted reproduction methods during the VZV infective period. © 2017 Blackwell Verlag GmbH.

The herpes zoster subunit vaccine.

PubMed

Cunningham, Anthony L

2016-01-01

Herpes zoster (HZ) causes severe pain and rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN). HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often associated with age related or other causes of decreased T cell immunity. A concentrated live attenuated vaccine boosts this immunity and provides partial protection against HZ, but this decreases with age and declines over 5-8 years. The new HZ subunit (HZ/su or Shingrix) vaccine combines a key surface VZV glycoprotein (E) with T cell boosting adjuvant (AS01B). It is highly efficacious in protection (97%) against HZ in immunocompetent subjects, with no decline in advancing age and protection maintained for >3 years. Phase I-II trials showed safety and similar immunogenicity in severely immunocompromised patients. Local injection site pain and swelling can be severe in a minority (9.5%) but is transient (2 days). The HZ/su vaccine appears very promising in immunocompetent patients in the ZoE-50 controlled trial. The unblinding of the current ZoE-50 trial and publication of results from the accompanying ZoE-70 trial will reveal more about its mechanism of action and its efficacy against PHN, particularly in subjects >70 years. Phase III trial results in immunocompromised patients are eagerly awaited.

Herpes zoster vaccine and the incidence of recurrent herpes zoster in an immunocompetent elderly population.

PubMed

Tseng, Hung Fu; Chi, Margaret; Smith, Ning; Marcy, Stephen M; Sy, Lina S; Jacobsen, Steven J

2012-07-15

The benefit of vaccinating immunocompetent patients who have had shingles has not been examined. The study assessed the association between vaccination and the incidence of herpes zoster recurrence among persons with a recent episode of clinically diagnosed herpes zoster. This is a matched cohort study in Kaiser Permanente Southern California. Study populations were immunocompetent elderly individuals ≥ 60 years old with a recent episode of herpes zoster. Incidence of recurrent herpes zoster was compared between the vaccinated and the unvaccinated matched cohorts. A total of 1036 vaccinated and 5180 unvaccinated members were included. On the basis of clinically confirmed cases, the incidence of recurrent herpes zoster among persons aged <70 years was 0.99 (95% confidence interval [CI], .02-5.54) and 2.20 (95% CI, 1.10-3.93) cases per 1000 person-years in the vaccinated and unvaccinated cohorts, respectively. The adjusted hazard ratio was 0.39 (95% CI, .05-4.45) among persons aged <70 years and 1.05 (95% CI, .30-3.69) among persons aged ≥ 70 years. The risk of herpes zoster recurrence following a recent initial episode is fairly low among immunocompetent adults, regardless of vaccination status. Such a low risk suggests that one should evaluate the necessity of immediately vaccinating immunocompetent patients who had a recent herpes zoster episode.

Diagnostic significance of intrathecally produced herpes simplex and varizella-zoster virus-specific antibodies in central nervous system infections.

PubMed

Schultze, Detlev; Weder, Bruno; Cassinotti, Pascal; Vitek, Lucie; Krausse, Konrad; Fierz, Walter

2004-11-27

The optimal strategy for the diagnosis of herpes simplex virus (HSV) and varizella-zoster virus (VZV) disease of the central nervous system is the detection of viral DNA by polymerase chain reaction assay (PCR) in cerebrospinal fluid (CSF) and the examination of intrathecal production of specific antibodies. However, in acute neurological disease caused by either HSV or VZV, dual intrathecal synthesis of HSV-1, 2- as well as VZV-specific antibodies may be detectable and thus can hamper accurate aetiological diagnosis. This paper illustrates such equivocal findings in two case reports, investigates their frequency and discusses the possible reasons. Consecutive CSF/serum pairs of two patients with central nervous system (CNS) disease were tested by HSV-1-, HSV-2-, and VZV-specific PCR and by different serological assays for detection of neurotropic viruses and bacteria. Additionally, the results of microbiological investigations of 1'155 CSF/serum samples were retrospectively analyzed for coincident intrathecal antibody synthesis against HSV-1, 2 and VZV. Although only HSV-1 and VZV-specific DNA was detectable in the CSF of two patients with encephalitis and chronic meningitis, respectively, increasing intrathecal antibody production against both virus species could be demonstrated. Retrospective analysis of 1155 CSF/serum pairs revealed 55 (4.8%) pairs with evidence for intrathecally produced antibodies against either HSV-1, 2 (30/55) or VZV (14/55). Eleven of these 55 (20%) pairs showed intrathecal antibody-production against both virus species. Patients with CNS infection with HSV and VZV can be diagnosed by detecting intrathecally produced virus-specific antibodies, in addition to virus-specific PCR. However, in an appreciable proportion of patients a correct diagnosis is hampered by coincidentally detected antibodies in CSF against both virus species. Possible reasons for these equivocal findings are given.

Pulsed Radiofrequency to the Dorsal Root Ganglion in Acute Herpes Zoster and Postherpetic Neuralgia.

PubMed

Kim, Koohyun; Jo, Daehyun; Kim, EungDon

2017-03-01

Latent varicella zoster virus reactivates mainly in sensory ganglia such as the dorsal root ganglion (DRG) or trigeminal ganglion. The DRG contains many receptor channels and is an important region for pain signal transduction. Sustained abnormal electrical activity to the spinal cord via the DRG in acute herpes zoster can result in neuropathic conditions such as postherpetic neuralgia (PHN). Although the efficacy of pulsed radiofrequency (PRF) application to the DRG in various pain conditions has been previously reported, the application of PRF to the DRG in patients with herpes zoster has not yet been studied. The aim of the present study was to compare the clinical effects of PRF to the DRG in patients with herpes zoster to those of PRF to the DRG in patients with PHN. Retrospective comparative study. University hospital pain center in Korea. The medical records of 58 patients who underwent PRF to the DRG due to zoster related pain (herpes zoster or PHN) were retrospectively analyzed. Patients were divided into 2 groups according to the timing of PRF after zoster onset: an early PRF group (within 90 days) and a PHN PRF group (more than 90 days). The efficacy of PRF was assessed by a numeric rating scale (NRS) and by recording patient medication doses before PRF and at one week, 4 weeks, 8 weeks, and 12 weeks after PRF. Pain intensity was decreased after PRF in all participants. However, the degree of pain reduction was significantly higher in the early PRF group. Moreover, more patients discontinued their medication in the early PRF group, and the PRF success rate was also higher in the early PRF group. The relatively small sample size from a single center, short duration of review of medical records, and the retrospective nature of the study. PRF to the DRG is a useful treatment for treatment-resistant cases of herpes zoster and PHN. Particularly in herpes zoster patients with intractable pain, application of PRF to the DRG should be considered for pain control

Administrative Data to Explore the Role of Family History as a Risk Factor for Herpes Zoster.

PubMed

Harpaz, Rafael; Dahl, Rebecca M

2018-06-01

We used administrative data to study the impact of family history on the risk of herpes zoster (HZ). Our HZ cases and our HZ family history were both ascertained on the basis of medically attended diagnoses, without reliance on self-report or recall bias. Family history was associated with HZ risk among both siblings and parents. The strength of the association differed when the index child was latently infected with vaccine-strain vs wild-type varicella zoster virus. Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

A Viral-Human Interactome Based on Structural Motif-Domain Interactions Captures the Human Infectome

PubMed Central

Guo, Xianwu; Rodríguez-Pérez, Mario A.

2013-01-01

Protein interactions between a pathogen and its host are fundamental in the establishment of the pathogen and underline the infection mechanism. In the present work, we developed a single predictive model for building a host-viral interactome based on the identification of structural descriptors from motif-domain interactions of protein complexes deposited in the Protein Data Bank (PDB). The structural descriptors were used for searching, in a database of protein sequences of human and five clinically important viruses; therefore, viral and human proteins sharing a descriptor were predicted as interacting proteins. The analysis of the host-viral interactome allowed to identify a set of new interactions that further explain molecular mechanism associated with viral infections and showed that it was able to capture human proteins already associated to viral infections (human infectome) and non-infectious diseases (human diseasome). The analysis of human proteins targeted by viral proteins in the context of a human interactome showed that their neighbors are enriched in proteins reported with differential expression under infection and disease conditions. It is expected that the findings of this work will contribute to the development of systems biology for infectious diseases, and help guide the rational identification and prioritization of novel drug targets. PMID:23951184

A CONTRIBUTION TO THE PATHOGENETIC PROBLEM OF HERPES ZOSTER IN THE COURSE OF IRRADIATED NEOPLASMS (PRESENTATION OF 21 PERSONAL CASES) (in Italian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ciampelli, I.; Crocella, R.

1962-06-01

Cases of Herpes Zoster observed in patients with neoplasms who were undergoing radiation or chemotherapeutic treatment are reported. Although no statistical value is attributed to the caselist, the higher incidence of symptomatic Zoster in systemic forms and particularly in lymphogranuloma is confirmed. On the basis of the concept of conditioned infectious disease, it is believed that the taking of the Herpes virus is mainly favored by the fall in the body's defense powers. The local effect of the ionizing radiations or of the neoplasm itself might have a certain value in localizing the virus in a given nervous segment. (auth)

The Topology of the Growing Human Interactome Data.

PubMed

Janjić, Vuk; Pržulj, Nataša

2014-06-01

We have long moved past the one-gene-one-function concept originally proposed by Beadle and Tatum back in 1941; but the full understanding of genotype-phenotype relations still largely relies on the analysis of static, snapshot-like, interaction data sets. Here, we look at what global patterns can be uncovered if we simply trace back the human interactome network over the last decade of protein-protein interaction (PPI) screening. We take a purely topological approach and find that as the human interactome is getting denser, it is not only gaining in structure (in terms of now being better fit by structured network models than before), but also there are patterns in the way in which it is growing: (a) newly added proteins tend to get linked to existing proteins in the interactome that are not know to interact; and (b) new proteins tend to link to already well connected proteins. Moreover, the alignment between human and yeast interactomes spanning over 40% of yeast's proteins - that are involved in regulation of transcription, RNA splicing and other cellcycle- related processes-suggests the existence of a part of the interactome which remains topologically and functionally unaffected through evolution. Furthermore, we find a small sub-network, specific to the "core" of the human interactome and involved in regulation of transcription and cancer development, whose wiring has not changed within the human interactome over the last 10 years of interacome data acquisition. Finally, we introduce a generalisation of the clustering coefficient of a network as a new measure called the cycle coefficient, and use it to show that PPI networks of human and model organisms are wired in a tight way which forbids the occurrence large cycles.

The topology of the growing human interactome data.

PubMed

Janjić, Vuk; Pržulj, Nataša

2014-06-23

We have long moved past the one-gene–one-function concept originally proposed by Beadle and Tatum back in 1941; but the full understanding of genotype–phenotype relations still largely relies on the analysis of static, snapshot-like, interaction data sets. Here, we look at what global patterns can be uncovered if we simply trace back the human interactome network over the last decade of protein- protein interaction (PPI) screening. We take a purely topological approach and find that as the human interactome is getting denser, it is not only gaining in structure (in terms of now being better fit by structured network models than before), but also there are patterns in the way in which it is growing: (a) newly added proteins tend to get linked to existing proteins in the interactome that are not know to interact; and (b) new proteins tend to link to already well connected proteins. Moreover, the alignment between human and yeast interactomes spanning over 40% of yeast’s proteins — that are involved in regulation of transcription, RNA splicing and other cellcycle-related processes—suggests the existence of a part of the interactome which remains topologically and functionally unaffected through evolution. Furthermore, we find a small sub-network, specific to the “core” of the human interactome and involved in regulation of transcription and cancer development, whose wiring has not changed within the human interactome over the last 10 years of interacome data acquisition. Finally, we introduce a generalisation of the clustering coefficient of a network as a new measure called the cycle coefficient, and use it to show that PPI networks of human and model organisms are wired in a tight way which forbids the occurrence large cycles.

System-wide identification of RNA-binding proteins by interactome capture.

PubMed

Castello, Alfredo; Horos, Rastislav; Strein, Claudia; Fischer, Bernd; Eichelbaum, Katrin; Steinmetz, Lars M; Krijgsveld, Jeroen; Hentze, Matthias W

2013-03-01

Owing to their preeminent biological functions, the repertoire of expressed RNA-binding proteins (RBPs) and their activity states are highly informative about cellular systems. We have developed a novel and unbiased technique, called interactome capture, for identifying the active RBPs of cultured cells. By making use of in vivo UV cross-linking of RBPs to polyadenylated RNAs, covalently bound proteins are captured with oligo(dT) magnetic beads. After stringent washes, the mRNA interactome is determined by quantitative mass spectrometry (MS). The protocol takes 3 working days for analysis of single proteins by western blotting, and about 2 weeks for the determination of complete cellular mRNA interactomes by MS. The most important advantage of interactome capture over other in vitro and in silico approaches is that only RBPs bound to RNA in a physiological environment are identified. When applied to HeLa cells, interactome capture revealed hundreds of novel RBPs. Interactome capture can also be broadly used to compare different biological states, including metabolic stress, cell cycle, differentiation, development or the response to drugs.

Rapid, Optimized Interactomic Screening

PubMed Central

Hakhverdyan, Zhanna; Domanski, Michal; Hough, Loren; Oroskar, Asha A.; Oroskar, Anil R.; Keegan, Sarah; Dilworth, David J.; Molloy, Kelly R.; Sherman, Vadim; Aitchison, John D.; Fenyö, David; Chait, Brian T.; Jensen, Torben Heick; Rout, Michael P.; LaCava, John

2015-01-01

We must reliably map the interactomes of cellular macromolecular complexes in order to fully explore and understand biological systems. However, there are no methods to accurately predict how to capture a given macromolecular complex with its physiological binding partners. Here, we present a screen that comprehensively explores the parameters affecting the stability of interactions in affinity-captured complexes, enabling the discovery of physiological binding partners and the elucidation of their functional interactions in unparalleled detail. We have implemented this screen on several macromolecular complexes from a variety of organisms, revealing novel profiles even for well-studied proteins. Our approach is robust, economical and automatable, providing an inroad to the rigorous, systematic dissection of cellular interactomes. PMID:25938370

Herpes zoster vaccine effectiveness against incident herpes zoster and post-herpetic neuralgia in an older US population: a cohort study.

PubMed

Langan, Sinéad M; Smeeth, Liam; Margolis, David J; Thomas, Sara L

2013-01-01

Herpes zoster is common and has serious consequences, notably post-herpetic neuralgia (PHN). Vaccine efficacy against incident zoster and PHN has been demonstrated in clinical trials, but effectiveness has not been studied in unselected general populations unrestricted by region, full health insurance coverage, or immune status. Our objective was to assess zoster vaccine effectiveness (VE) against incident zoster and PHN in a general population-based setting. A cohort study of 766,330 fully eligible individuals aged ≥ 65 years was undertaken in a 5% random sample of Medicare who received and did not receive zoster vaccination between 1st January 2007 and 31st December 2009. Incidence rates and hazard ratios for zoster and PHN were determined in vaccinated and unvaccinated individuals. Analyses were adjusted for age, gender, race, low income, immunosuppression, and important comorbidities associated with zoster, and then stratified by immunosuppression status. Adjusted hazard ratios were estimated using time-updated Cox proportional hazards models. Vaccine uptake was low (3.9%) particularly among black people (0.3%) and those with evidence of low income (0.6%). 13,112 US Medicare beneficiaries developed incident zoster; the overall zoster incidence rate was 10.0 (9.8-10.2) per 1,000 person-years in the unvaccinated group and 5.4 (95% CI 4.6-6.4) per 1,000 person-years in vaccinees, giving an adjusted VE against incident zoster of 0.48 (95% CI 0.39-0.56). In immunosuppressed individuals, VE against zoster was 0.37 (95% CI 0.06-0.58). VE against PHN was 0.59 (95% CI 0.21-0.79). Vaccine uptake was low with variation in specific patient groups. In a general population cohort of older individuals, zoster vaccination was associated with reduction in incident zoster, including among those with immunosuppression. Importantly, this study demonstrates that zoster vaccination is associated with a reduction in PHN. Please see later in the article for the Editors' Summary.

Herpes Zoster Vaccine Effectiveness against Incident Herpes Zoster and Post-herpetic Neuralgia in an Older US Population: A Cohort Study

PubMed Central

Langan, Sinéad M.; Smeeth, Liam; Margolis, David J.; Thomas, Sara L.

2013-01-01

Background Herpes zoster is common and has serious consequences, notably post-herpetic neuralgia (PHN). Vaccine efficacy against incident zoster and PHN has been demonstrated in clinical trials, but effectiveness has not been studied in unselected general populations unrestricted by region, full health insurance coverage, or immune status. Our objective was to assess zoster vaccine effectiveness (VE) against incident zoster and PHN in a general population-based setting. Methods and Findings A cohort study of 766,330 fully eligible individuals aged ≥65 years was undertaken in a 5% random sample of Medicare who received and did not receive zoster vaccination between 1st January 2007 and 31st December 2009. Incidence rates and hazard ratios for zoster and PHN were determined in vaccinated and unvaccinated individuals. Analyses were adjusted for age, gender, race, low income, immunosuppression, and important comorbidities associated with zoster, and then stratified by immunosuppression status. Adjusted hazard ratios were estimated using time-updated Cox proportional hazards models. Vaccine uptake was low (3.9%) particularly among black people (0.3%) and those with evidence of low income (0.6%). 13,112 US Medicare beneficiaries developed incident zoster; the overall zoster incidence rate was 10.0 (9.8–10.2) per 1,000 person-years in the unvaccinated group and 5.4 (95% CI 4.6–6.4) per 1,000 person-years in vaccinees, giving an adjusted VE against incident zoster of 0.48 (95% CI 0.39–0.56). In immunosuppressed individuals, VE against zoster was 0.37 (95% CI 0.06–0.58). VE against PHN was 0.59 (95% CI 0.21–0.79). Conclusions Vaccine uptake was low with variation in specific patient groups. In a general population cohort of older individuals, zoster vaccination was associated with reduction in incident zoster, including among those with immunosuppression. Importantly, this study demonstrates that zoster vaccination is associated with a reduction in PHN. Please

Herpes zoster producing temporary erectile dysfunction.

PubMed

Rix, G H; Carroll, D N; MacFarlane, J R

2001-12-01

Varicella Zoster affecting the sacral dermatomes is a rare but well recognised cause of urinary retention. Only one case of erectile dysfunction associated with Varicella Zoster has previously been described, which was longstanding, but no cases of transient erectile dysfunction following Zoster infection are recorded. We present one such case.

Varicella zoster virus infections in Canadian children in the prevaccine era: A hospital-based study

PubMed Central

Kuhn, Susan; Davies, H Dele; Jadavji, Taj

1997-01-01

OBJECTIVE: To describe the clinical course of children admitted for varicella zoster virus (VZV) infections to a pediatric hospital before the release of VZV vaccine in Canada. DESIGN: Retrospective case series. SETTING: Tertiary pediatric hospital. Population studied was children aged 18 years or younger admitted to hospital between 1983 and 1992 who were discharged with a diagnosis of varicella or zoster. Of the 201 children who were identified, 36 were excluded, leaving 165 for analysis. RESULTS: There was a male:female ratio of 1.5:1 and a median age of 5.3 years (range two weeks to 18 years). The group included those who were previously healthy (70, 42.4%), immunocompromised (60, 36.4%), and those with nonimmunocompromising conditions (35, 21.2%). Comparison of immunocompetent and immunocompromised children revealed that complication of VZV infection was a more common reason for admission among the former (86 of 105, 81.9%, P<0.001), whereas treatment with acyclovir to limit dissemination was the most common reason in the latter (53 of 60, 88.3%, P<0.001). Skin and soft tissue infections were the most common complications in immunocompetent children (36 of 98) and those younger than five years (26 of 53), whereas pulmonary complications predominated among immunocompromised patients (eight of 98) and neurological complications in five- to 10-year-olds (16 of 36). Only one death (0.6%) occurred in an immunocompetent patient. Group A beta-hemolytic streptococci and Staphylococcus aureus caused equal numbers of secondary infections (92% of all isolates). CONCLUSIONS: Complications of VZV infections and secondary prophylactic antiviral treatment of immunocompromised children explain the majority of hospitalizations in this institution, and can be monitored after VZV vaccine introduction. Complications vary significantly with underlying healthy status and age. PMID:22346528

Errant processing and structural alterations of genomes present in a varicella-zoster virus vaccine.

PubMed Central

Vlazny, D A; Hyman, R W

1985-01-01

Five minority populations of aberrant, varicella-zoster virus (VZV)-derived genomes were identified among the encapsidated DNAs obtained from the nuclear and cytoplasmic fractions of an in vitro infection initiated with a lyophilized sample of the BIKEN VZV vaccine (strain Oka). These were (i) VZV genomes, present within nuclear but not cytoplasmic viral capsids, which had been cleaved at a specific site within the short segment and which were, therefore, 3.15 megadaltons (approximately 4% of the VZV genome length) short of full length; (ii) highly deleted, repetitive VZV genomes which contained the errant cleavage site but not the usual VZV genome terminal sequences; (iii) VZV genomes into which multiples of 1 through 5 defective genome repeat units had been inserted into a homologous site; (iv) VZV genomes with additions of 0.1 or 0.18 megadaltons of DNA at both the terminal and internal ends of the short segment; and (v) VZV DNA which had lost the HindIII restriction site at map position 0.11. Images PMID:2993670

Zoster vaccination is associated with a reduction of zoster in elderly patients with chronic kidney disease.

PubMed

Langan, Sinéad M; Thomas, Sara L; Smeeth, Liam; Margolis, David J; Nitsch, Dorothea

2016-12-01

Growing epidemiological evidence demonstrates increased zoster risks in people with chronic kidney disease (CKD). Study objectives were to determine zoster vaccine effectiveness in individuals with CKD in pragmatic use. A population-based cohort study was undertaken in a 5% random sample of US Medicare from 2007 to 2009 involving 766 330 eligible individuals aged ≥65 years who were (29 785) and were not (736 545) exposed to the zoster vaccine. Incidence rates for zoster in vaccinated and unvaccinated individuals and hazard ratios for zoster comparing vaccinated with unvaccinated were determined for individuals with CKD. Time-updated Cox proportional hazards models were used, adjusting for relevant confounders. CKD was present in 183 762 (24%) of individuals (15% of vaccinees). Adjusted vaccine effectiveness [95% confidence intervals (CIs)] in individuals with CKD was 0.49 (0.36-0.65). The adjusted vaccine effectiveness in participants with both CKD and diabetes mellitus was 0.46 (95% CI 0.09-0.68). Vaccine effectiveness estimates were similar to those previously reported for the general population [vaccine effectiveness 0.48 (95% CI 0.39-0.56)]. Zoster vaccine is effective against incident zoster in older individuals with CKD. Extra efforts are warranted to increase vaccine uptake in individuals with CKD given the known low uptake in these higher risk individuals. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

Development and clinical validation of a multiplex real-time PCR assay for herpes simplex and varicella zoster virus.

PubMed

Tan, Thean Yen; Zou, Hao; Ong, Danny Chee Tiong; Ker, Khor Jia; Chio, Martin Tze Wei; Teo, Rachael Yu Lin; Koh, Mark Jean Aan

2013-12-01

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are related members of the Herpesviridae family and are well-documented human pathogens causing a spectrum of diseases, from mucocutaneous disease to infections of the central nervous system. This study was carried out to evaluate and validate the performance of a multiplex real-time polymerase chain reaction (PCR) assay in detecting and differentiating HSV1, HSV2, and VZV from clinical samples. Consensus PCR primers for HSV were designed from the UL30 component of the DNA polymerase gene of HSV, with 2 separate hydrolysis probes designed to differentiate HSV1 and HSV2. Separate primers and a probe were also designed against the DNA polymerase gene of VZV. A total of 104 clinical samples were available for testing by real-time PCR, conventional PCR, and viral culture. The sensitivity and specificity of the real-time assay was calculated by comparing the multiplex PCR result with that of a combined standard of virus culture and conventional PCR. The sensitivity of the real-time assay was 100%, with specificity ranging from 98% to 100% depending on the target gene. Both PCR methods detected more positive samples for HSV or VZV, compared with conventional virus culture. This multiplex PCR assay provides accurate and rapid diagnostic capabilities for the diagnosis and differentiation of HSV1, HSV2, and VZV infections, with the presence of an internal control to monitor for inhibition of the PCR reaction.

FV-100: the most potent and selective anti-varicella zoster virus agent reported to date.

PubMed

Migliore, Marco

2010-01-05

Bicyclic aryl furano pyrimidines represent the most potent anti-varicella zoster virus (VZV) agents reported to date. Lead compounds have 50% effective concentration (EC(50)) values in vitro that are in the subnanomolar range and selectivity index values that exceed 1 million. They have an absolute requirement for VZV thymidine kinase and most likely act as their phosphate forms. Some structural modification (such as aryl substitution in the base moiety) is tolerated, whereas little sugar modification is acceptable. The Cf1743 compound has proved to be significantly more potent than all reference anti-VZV compounds, as measured either by inhibition of infectious virus particles and/or viral DNA production; however, the high lipophilicity and very low water solubility of this compound gives poor oral bioavailability (<14%). Use of the modified cyclodextrin captisol and the synthesis of the 5'-monophosphate prodrug of Cf1743 has significantly improved water solubility, but does not give any enhancement in oral bioavailability. By contrast, the synthesis of the ether series does not give any further improvement in terms of solubility. The most promising prodrug to emerge to date is the hydrochloric salt of the 5'-valyl-ester, designated as FV-100. Its uptake into cells has been studied using fluorescent microscopy and biological assays, which have indicated that the compound is efficiently taken up by the cells after a short period of incubation.

Herpes zoster (shingles) disseminated (image)

MedlinePlus

Herpes zoster (shingles) normally occurs in a limited area that follows a dermatome (see the "dermatome" picture). In individuals with damaged immune systems, herpes zoster may be widespread (disseminated), causing serious illness. ...

Longitudinal analysis of varicella-zoster virus-specific antibodies in systemic lupus erythematosus: No association with subclinical viral reactivations or lupus disease activity.

PubMed

Rondaan, C; van Leer, C C; van Assen, S; Bootsma, H; de Leeuw, K; Arends, S; Bos, N A; Westra, J

2018-07-01

Systemic lupus erythematosus (SLE) patients are at high risk of herpes zoster. Previously, we found increased immunoglobulin (Ig)G levels against varicella-zoster virus (VZV) in SLE patients compared to controls, while antibody levels against diphtheria and cellular immunity to VZV were decreased. We aimed to test our hypothesis that increased VZV-IgG levels in SLE result from subclinical VZV reactivations, caused by stress because of lupus disease activity or immunosuppressive drug use. Methods Antibody levels to VZV (IgG, IgA, IgM), total IgG and VZV-DNA were longitudinally determined in the serum of 34 SLE patients, using enzyme-linked immunosorbent assay and polymerase chain reaction. Clinical data were retrieved from medical records. Reactivation of VZV was defined as an at least fivefold rise in VZV-IgG or presence of VZV-IgM or VZV-DNA. Generalized estimating equations (GEE) were used to longitudinally analyse associations between antibody levels, lupus disease activity and medication use. Systemic Lupus Erythematosus Disease Activity Index, anti-double-stranded DNA and complement levels were used as indicators of lupus disease activity. Results A VZV reactivation was determined in 11 patients (33%). In at least five of them, herpes zoster was clinically overt. No association between SLE disease activity or medication use and VZV-specific antibody levels was found. There was a weak association between total IgG and VZV-IgG. Conclusions Our results indicate that increased VZV-IgG levels in SLE do not result from frequent subclinical VZV reactivations, and are not associated with lupus disease activity. Increased VZV-IgG can only partially be explained by hypergammaglobulinaemia.

Zoster duplex: a clinical report and etiologic analysis.

PubMed

Zhang, Feng; Zhou, Jin

2015-01-01

Herpes zoster (HZ) duplex is a rare disease presentation. The mechanisms of varicella zoster virus (VZV) reactivation in multiple dermal regions are unknown. To present a HZ duplex case occurring in an immunocompetent woman and to analyze the possible underlying causes of HZ duplex. We present a HZ duplex case in an immunocompetent woman and analyzed the possible contributing factors in 36 HZ duplex cases. Continuously distributed variables were categorized by numbers and percentages. In our study, 24 cases (66.7%) were from Asia, 16 cases (44.4%) were in individuals ≥ 50 years of age, and 17 cases (47.2%) occurred in immunocompromised patients. Of the 36 cases, 23 involved women (63.9%) and 13 involved men. Eighteen patients suffering from HZ duplex, 13 of which were women (72.2%), did not suffer from any chronic systemic disease or have a long history of taking drugs. HZ duplex is a rare event that can occur in both immunocompetent and immunosuppressed individuals. HZ duplex might be associated with the Asia region, advanced age, immunosuppression, and being female.

Varicella-zoster virus immunity among health care workers in Catalonia.

PubMed

Urbiztondo, L; Bayas, J M; Broner, S; Costa, J; Esteve, M; Campins, M; Borrás, E; Domínguez, A

2014-10-14

To determine varicella-zoster virus (VZV) immunity among healthcare workers (HCWs). Cross-sectional study. HCWs attending voluntary periodic health examinations between June 2008 and December 2010. Six public hospitals and five primary care areas in Catalonia, Spain. A self-administered questionnaire was given to eligible HCWs. Variables including age, sex, professional category, type of centre, history of varicella infection, and VZV vaccination were collected. The study was carried out using a convenience sample. The prevalence of antibodies and positive and negative predictive values (PPV and NPV) of the history of clinical VZV infection or vaccination were calculated. Crude and adjusted odds ratios (OR and ORa) and their 95% confidence intervals (CI) were calculated to determine the variables associated with antibody prevalence. Of 705 HCWs who agreed to participate, 644 were finally included. The overall prevalence of antibodies to varicella was 94.9% (95% CI: 92.9-96.4). Of the variables studied, only age was associated with serological susceptibility to VZV. HCWs aged 25-35 years had the highest serological susceptibility (8.1%, 95% CI: 4.6-13.0). The prevalence of antibodies was 96% in subjects reporting previous VZV infection or vaccination, compared with 93% in subjects who did not report these states or did not know. The high proportion of serologically-susceptible HCWs found in this study indicates the need to develop for screening and vaccination strategies in Catalonia. Due to the high capacity of propagation of the VZV in health settings and its consequences, VZV vaccination programmes in HCWs should be reinforced. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neuronal Subtype and Satellite Cell Tropism Are Determinants of Varicella-Zoster Virus Virulence in Human Dorsal Root Ganglia Xenografts In Vivo

PubMed Central

Zerboni, Leigh; Arvin, Ann

2015-01-01

Varicella zoster virus (VZV), a human alphaherpesvirus, causes varicella during primary infection. VZV reactivation from neuronal latency may cause herpes zoster, post herpetic neuralgia (PHN) and other neurologic syndromes. To investigate VZV neuropathogenesis, we developed a model using human dorsal root ganglia (DRG) xenografts in immunodeficient (SCID) mice. The SCID DRG model provides an opportunity to examine characteristics of VZV infection that occur in the context of the specialized architecture of DRG, in which nerve cell bodies are ensheathed by satellite glial cells (SGC) which support neuronal homeostasis. We hypothesized that VZV exhibits neuron-subtype specific tropism and that VZV tropism for SGC contributes to VZV-related ganglionopathy. Based on quantitative analyses of viral and cell protein expression in DRG tissue sections, we demonstrated that, whereas DRG neurons had an immature neuronal phenotype prior to implantation, subtype heterogeneity was observed within 20 weeks and SGC retained the capacity to maintain neuronal homeostasis longterm. Profiling VZV protein expression in DRG neurons showed that VZV enters peripherin+ nociceptive and RT97+ mechanoreceptive neurons by both axonal transport and contiguous spread from SGC, but replication in RT97+ neurons is blocked. Restriction occurs even when the SGC surrounding the neuronal cell body were infected and after entry and ORF61 expression, but before IE62 or IE63 protein expression. Notably, although contiguous VZV spread with loss of SGC support would be predicted to affect survival of both nociceptive and mechanoreceptive neurons, RT97+ neurons showed selective loss relative to peripherin+ neurons at later times in DRG infection. Profiling cell factors that were upregulated in VZV-infected DRG indicated that VZV infection induced marked pro-inflammatory responses, as well as proteins of the interferon pathway and neuroprotective responses. These neuropathologic changes observed in sensory

RASopathies: Presentation at the Genome, Interactome, and Phenome Levels.

PubMed

Pevec, Urska; Rozman, Neva; Gorsek, Blaz; Kunej, Tanja

2016-05-01

Clinical symptoms often reflect molecular correlations between mutated proteins. Alignment between interactome and phenome levels reveals new disease genes and connections between previously unrelated diseases. Despite a great potential for novel discoveries, this approach is still rarely used in genomics. In the present study, we analyzed the data of 6 syndromes belonging to the RASopathy class of disorders (RASopathies) and presented them as a model to study associations between genome, interactome, and phenome levels. Causative genes and clinical symptoms were collected from OMIM and NCBI GeneReviews databases for 6 syndromes: Noonan, Noonan syndrome with multiple lentigines, neurofibromatosis type 1, cardiofaciocutaneous, and Legius and Costello syndrome. The STRING tool was used for the identification of protein interactions. Six RASopathy syndromes were found to be associated with 12 causative genes. We constructed an interactome of RASopathy proteins and their neighbors and developed a database of 328 clinical symptoms. The collected data was presented at genome, interactome, and phenome levels and as an integrated network of all 3 data types. The present study provides a baseline for future studies of associations between interactome and phenome in RASopathies and could serve as a novel approach to analyze phenotypically and genetically related diseases.

Disease burden of herpes zoster in Korea.

PubMed

Choi, Won Suk; Noh, Ji Yun; Huh, Joong Yeon; Jo, Yu Mi; Lee, Jacob; Song, Joon Young; Kim, Woo Joo; Cheong, Hee Jin

2010-04-01

The occurrence of herpes zoster can deteriorate the quality of life considerably, resulting in high disease burden. While Korea is assumed to have high disease burden of herpes zoster, there has been no researches analyzing this. We performed this study to investigate the disease burden of herpes zoster in the Korean population as a whole. We used the database of the Health Insurance Review & Assessment Service of Korea and analyzed the data of patients who had herpes zoster as a principal diagnosis during the period from 2003 to 2007. We investigated the annual prevalence, rate of clinical visits, rate of hospitalization, and the pattern of medical services use. The socioeconomic burden of herpes zoster was calculated by a conversion into cost. Rates of clinic visits and hospitalizations due to herpes zoster during the 5-year period from 2003 to 2007 were 7.93-12.54 per 1000 population and 0.22-0.32 per 1000 population, respectively. Prevalence rates according to age increased sharply after 50 years and reached a peak at 70 years. The total socioeconomic cost of herpes zoster was $75.9-143.8 million per year, increasing every year by 14-20%. There is a heavy socioeconomic burden due to herpes zoster in Korea and indicate that appropriate policies need to be established to reduce this burden. Additional researches are also necessary to assess the safety, efficacy and cost-effectiveness of a herpes zoster vaccine in the Korean population. Copyright 2010 Elsevier B.V. All rights reserved.

A Unique Case of Acute Cerebral Venous Sinus Thrombosis Secondary to Primary Varicella Zoster Virus Infection.

PubMed

Imam, Syed F; Lodhi, Omair Ul Haq; Fatima, Zainab; Nasim, Saneeya; Malik, Waseem T; Saleem, Muhammad Sabih

2017-09-16

Primary varicella zoster virus (VZV) infection, predominantly in the pediatric population, presents with pyrexia and a classic pruritic vesicular rash. In adults, although less common, it is more severe and linked to more complications. Neurological complications, which account for less than 1% of all VZV complications, include meningitis, encephalitis, arterial vasculopathy, and venous thrombosis. We present a case of a 39-year-old male who developed extensive cerebral venous sinus thrombosis following primary VZV infection. Venous thrombosis in VZV has been suggested to be caused by autoantibodies against protein S, pre-existing hypercoagulability, or endothelial damage. The patient was acutely managed using intravenous acyclovir and heparin. Long-term anticoagulation therapy with warfarin was continued after discharge. We concluded that clinicians should be aware of the rare complications of this common pathology so that a timely diagnosis can be made, followed by prompt management. Further studies need to be done to better understand acute cerebral venous sinus thrombosis secondary to VZV.

Open Reading Frame S/L of Varicella-Zoster Virus Encodes a Cytoplasmic Protein Expressed in Infected Cells

PubMed Central

Kemble, George W.; Annunziato, Paula; Lungu, Octavian; Winter, Ruth E.; Cha, Tai-An; Silverstein, Saul J.; Spaete, Richard R.

2000-01-01

We report the discovery of a novel gene in the varicella-zoster virus (VZV) genome, designated open reading frame (ORF) S/L. This gene, located at the left end of the prototype VZV genome isomer, expresses a polyadenylated mRNA containing a splice within the 3′ untranslated region in virus-infected cells. Sequence analysis reveals significant differences between the ORF S/Ls of wild-type and attenuated strains of VZV. Antisera raised to a bacterially expressed portion of ORF S/L reacted specifically with a 21-kDa protein synthesized in cells infected with a VZV clinical isolate and with the original vaccine strain of VZV (Oka-ATCC). Cells infected with other VZV strains, including a wild-type strain that has been extensively passaged in tissue culture and commercially produced vaccine strains of Oka, synthesize a family of proteins ranging in size from 21 to 30 kDa that react with the anti-ORF S/L antiserum. MeWO cells infected with recombinant VZV harboring mutations in the C-terminal region of the ORF S/L gene lost adherence to the stratum and adjacent cells, resulting in an altered plaque morphology. Immunohistochemical analysis of VZV-infected cells demonstrated that ORF S/L protein localizes to the cytoplasm. ORF S/L protein was present in skin lesions of individuals with primary or reactivated infection and in the neurons of a dorsal root ganglion during virus reactivation. PMID:11070031

Association of progressive outer retinal necrosis and varicella zoster encephalitis in a patient with AIDS.

PubMed Central

van den Horn, G J; Meenken, C; Troost, D

1996-01-01

BACKGROUND: A patient with AIDS who developed the clinical picture of bilateral progressive outer retinal necrosis (PORN) in combination with varicella zoster encephalitis is described. The picture developed more than 2 years after an episode of ophthalmic zoster infection, and following intermittent exposure to oral acyclovir because of recurrent episodes of cutaneous herpes simplex infection. METHODS: Aqueous humour, obtained by paracentesis of the anterior chamber, was analysed using immunofluorescence and polymerase chain reaction (PCR). Postmortem analysis of eye and brain tissue was performed by using conventional techniques and in situ hybridisation. RESULTS: While conventional techniques all failed to detect a causative agent, analysis of the aqueous humour using PCR, and histological examination of necropsy specimens from eyes and brain using in situ hybridisation were conclusive for the diagnosis varicella zoster virus (VZV) infection. CONCLUSION: This case documents the presumed association of PORN and VZV encephalitis in a severely immunocompromised AIDS patient. Images PMID:8976726

Incidence of varicella zoster virus infections of the central nervous system in the elderly: a large tertiary hospital-based series (2007-2014).

PubMed

Arruti, M; Piñeiro, L D; Salicio, Y; Cilla, G; Goenaga, M A; López de Munain, A

2017-06-01

The aim of the study was to describe the clinical and epidemiological characteristics of the central nervous system (CNS) infection by varicella zoster virus (VZV) in patients older than 65 years in a tertiary community hospital. We retrospectively analysed the results of cerebrospinal fluid (CSF) testing in patients older than 65 years between 2007 and 2014 with clinically suspected VZV infection with CNS involvement. Patients whose CSF samples were positive for VZV DNA were included, as were those with negative results who simultaneously presented herpes zoster and CSF or magnetic resonance imaging findings suggestive of CNS infection, and in whom other possible aetiologies had been ruled out. The study included 280 patients. The disease was considered to be caused by a VZV infection in 32 patients (11.4%), of which 23 cases were virologically confirmed (detection of VZV DNA in CSF). The most frequent diagnosis of the patients with VZV CNS infection was encephalitis (83.3%), followed by meningitis (13.3%) and cerebellitis (3.3%). The mean annual incidence of VZV CNS infection was 3.0 cases per 100,000 inhabitants. VZV was the most common cause of encephalitis and viral meningitis, ahead of herpes simplex virus (n = 9). At the time of discharge, 12 (40%) patients showed neurological sequelae. Five patients (20%) died during hospitalization, all with encephalitis. Patients with a fatal outcome had significantly higher median age and longer delay before initiating acyclovir. In conclusion, VZV was the first cause of encephalitis in our elderly population. Despite acyclovir treatment, there was a high rate of case fatality and sequelae at discharge.

The distinctive cell division interactome of Neisseria gonorrhoeae.

PubMed

Zou, Yinan; Li, Yan; Dillon, Jo-Anne R

2017-12-12

Bacterial cell division is an essential process driven by the formation of a Z-ring structure, as a cytoskeletal scaffold at the mid-cell, followed by the recruitment of various proteins which form the divisome. The cell division interactome reflects the complement of different interactions between all divisome proteins. To date, only two cell division interactomes have been characterized, in Escherichia coli and in Streptococcus pneumoniae. The cell divison proteins encoded by Neisseria gonorrhoeae include FtsZ, FtsA, ZipA, FtsK, FtsQ, FtsI, FtsW, and FtsN. The purpose of the present study was to characterize the cell division interactome of N. gonorrhoeae using several different methods to identify protein-protein interactions. We also characterized the specific subdomains of FtsA implicated in interactions with FtsZ, FtsQ, FtsN and FtsW. Using a combination of bacterial two-hybrid (B2H), glutathione S-transferase (GST) pull-down assays, and surface plasmon resonance (SPR), nine interactions were observed among the eight gonococcal cell division proteins tested. ZipA did not interact with any other cell division proteins. Comparisons of the N. gonorrhoeae cell division interactome with the published interactomes from E. coli and S. pneumoniae indicated that FtsA-FtsZ and FtsZ-FtsK interactions were common to all three species. FtsA-FtsW and FtsK-FtsN interactions were only present in N. gonorrhoeae. The 2A and 2B subdomains of FtsA Ng were involved in interactions with FtsQ, FtsZ, and FtsN, and the 2A subdomain was involved in interaction with FtsW. Results from this research indicate that N. gonorrhoeae has a distinctive cell division interactome as compared with other microorganisms.

Towards Establishment of a Rice Stress Response Interactome

PubMed Central

Seo, Young-Su; Chern, Mawsheng; Bartley, Laura E.; Han, Muho; Jung, Ki-Hong; Lee, Insuk; Walia, Harkamal; Richter, Todd; Xu, Xia; Cao, Peijian; Bai, Wei; Ramanan, Rajeshwari; Amonpant, Fawn; Arul, Loganathan; Canlas, Patrick E.; Ruan, Randy; Park, Chang-Jin; Chen, Xuewei; Hwang, Sohyun; Jeon, Jong-Seong; Ronald, Pamela C.

2011-01-01

Rice (Oryza sativa) is a staple food for more than half the world and a model for studies of monocotyledonous species, which include cereal crops and candidate bioenergy grasses. A major limitation of crop production is imposed by a suite of abiotic and biotic stresses resulting in 30%–60% yield losses globally each year. To elucidate stress response signaling networks, we constructed an interactome of 100 proteins by yeast two-hybrid (Y2H) assays around key regulators of the rice biotic and abiotic stress responses. We validated the interactome using protein–protein interaction (PPI) assays, co-expression of transcripts, and phenotypic analyses. Using this interactome-guided prediction and phenotype validation, we identified ten novel regulators of stress tolerance, including two from protein classes not previously known to function in stress responses. Several lines of evidence support cross-talk between biotic and abiotic stress responses. The combination of focused interactome and systems analyses described here represents significant progress toward elucidating the molecular basis of traits of agronomic importance. PMID:21533176

Recombinant glycoprotein E produced in mammalian cells in large-scale as an antigen for varicella-zoster-virus serology.

PubMed

Thomsson, Elisabeth; Persson, Linn; Grahn, Anna; Snäll, Johanna; Ekblad, Maria; Brunhage, Eva; Svensson, Frida; Jern, Christina; Hansson, Gunnar C; Bäckström, Malin; Bergström, Tomas

2011-07-01

A recombinant glycoprotein E (gE) from varicella-zoster virus (VZV) was generated and produced in Chinese Hamster Ovary (CHO) cells, in the development of a specific antigen for analysis of IgG antibodies to VZV. Several stable gE-secreting clones were established and one clone was adapted to growth in serum-free suspension culture. When the cells were cultured in a perfusion bioreactor, gE was secreted into the medium, from where it could be easily purified. The recombinant gE was then evaluated as a serological antigen in ELISA. When compared to a conventional whole virus antigen, the VZV gE showed similar results in ELISA-based seroprevalence studies of 854 samples derived from blood donors, students, ischemic stroke patients and their controls, including samples with border-line results in previous analyses. Eight samples (0.9%) were discordant, all being IgG-negative by the VZV gE ELISA and positive by the whole virus ELISA. The sensitivity and specificity of the VZV gE ELISA were 99.9% and 100%, respectively, compared to 100% and 88.9% for the VZV whole virus ELISA. The elderly subjects showed similar reactivities to both antigens, while VZV gE gave lower signals in the younger cohorts, suggesting that antibodies to gE may increase with age. It was concluded that the recombinant VZV gE from CHO cells was suitable as a serological antigen for the detection of IgG antibodies specific for VZV. Copyright © 2011 Elsevier B.V. All rights reserved.

"Fuzziness" in the celular interactome: a historical perspective.

PubMed

Welch, G Rickey

2012-01-01

Some historical background is given for appreciating the impact of the empirical construct known as the cellular protein-protein interactome, which is a seemingly de novo entity that has arisen of late within the context of postgenomic systems biology. The approach here builds on a generalized principle of "fuzziness" in protein behavior, proposed by Tompa and Fuxreiter.(1) Recent controversies in the analysis and interpretation of the interactome studies are rationalized historically under the auspices of this concept. There is an extensive literature on protein-protein interactions, dating to the mid-1900s, which may help clarify the "fuzziness" in the interactome picture and, also, provide a basis for understanding the physiological importance of protein-protein interactions in vivo.

A systematic review of the cost effectiveness of herpes zoster vaccination.

PubMed

Szucs, Thomas D; Pfeil, Alena M

2013-02-01

The varicella zoster virus (VZV) can cause two infections: chickenpox or herpes zoster (HZ). Whereas chickenpox infections are normally mild but common among children, HZ infections are common among elderly people and can give rise to post-herpetic neuralgia (PHN), a severe and painful complication. This review aimed to summarize the literature available on the cost effectiveness of HZ vaccination and to summarize key issues for decision makers to consider when deciding on the reimbursement of HZ vaccination. We conducted a literature search of the databases PubMed and EMBASE using EndNote X4 from Thomson Reuters. The following combinations of keywords were used: 'herpes zoster vaccine' AND 'cost(-)effectiveness' or AND 'economic evaluation', 'herpes zoster vaccination' AND 'cost(-)effectiveness' or AND 'economic evaluation', 'varicella zoster vaccine' AND 'cost(-)effectiveness' or AND 'economic evaluation', and 'varicella zoster vaccination' AND 'cost(-)effectiveness' or AND 'economic evaluation'. A total of 11 studies were identified and included. Cost-effectiveness analyses of varicella zoster vaccination were excluded. The quality of the included studies ranged from 'moderate' to 'moderate to good' according to the British Medical Journal guidelines of Drummond and Jefferson and the Quality of Health Economic Studies (QHES) score of Ofman et al. Most studies evaluated the cost effectiveness of universal HZ vaccination in adults aged 50 years or 60 years and older. Data sources and model assumptions regarding epidemiology, utility estimates and costs varied between studies. All studies calculated costs per QALY, which allows comparing costs of interventions in different diseases. The costs per QALY gained and the incremental cost-effectiveness ratio (ICER) differed between studies depending on the age at vaccination, duration of vaccine efficacy, cost of vaccine course and economic perspective. All but one of the studies concluded that most vaccination

Use of a bacterial expression vector to map the varicella-zoster virus major glycoprotein gene, gC.

PubMed Central

Ellis, R W; Keller, P M; Lowe, R S; Zivin, R A

1985-01-01

The genome of varicella-zoster virus (VZV) encodes at least three major glycoprotein genes. Among viral gene products, the gC gene products are the most abundant glycoproteins and induce a substantial humoral immune response (Keller et al., J. Virol. 52:293-297, 1984). We utilized two independent approaches to map the gC gene. Small fragments of randomly digested VZV DNA were inserted into a bacterial expression vector. Bacterial colonies transformed by this vector library were screened serologically for antigen expression with monoclonal antibodies to gC. Hybridization of the plasmid DNA from a gC antigen-positive clone revealed homology to the 3' end of the VZV Us segment. In addition, mRNA from VZV-infected cells was hybrid selected by a set of VZV DNA recombinant plasmids and translated in vitro, and polypeptide products were immunoprecipitated by convalescent zoster serum or by monoclonal antibodies to gC. This analysis revealed that the mRNA encoding a 70,000-dalton polypeptide precipitable by anti-gC antibodies mapped to the HindIII C fragment, which circumscribes the entire Us region. We conclude that the VZV gC glycoprotein gene maps to the 3' end of the Us region and is expressed as a 70,000-dalton primary translational product. These results are consistent with the recently reported DNA sequence of Us (A.J. Davison, EMBO J. 2:2203-2209, 1983). Furthermore, glycosylation appears not to be required for a predominant portion of the antigenicity of gC glycoproteins. We also report the tentative map assignments for eight other VZV primary translational products. Images PMID:2981365

Herpes zoster correlates with pyogenic liver abscesses in Taiwan.

PubMed

Mei-Ling, Shen; Kuan-Fu, Liao; Sung-Mao, Tsai; Cheng-Li, Lin Ms; Shih-Wei, Lai

2016-12-01

The purpose of the paper was to explore the relationship between herpes zoster and pyogenic liver abscesses in Taiwan. This was a nationwide cohort study. Using the database of the Taiwan National Health Insurance Program, there were 33049 subjects aged 20-84 years who were newly diagnosed with herpes zoster from 1998 to 2010 that were selected for our study, and they were our herpes zoster group. 131707 randomly selected subjects without herpes zoster were our non-herpes zoster group. Both groups were matched by sex, age, other comorbidities, and the index year of their herpes zoster diagnosis. The incidence of pyogenic liver abscesses at the end of 2011 was then estimated. The multivariable Cox proportional hazard regression model was used to estimate the hazard ratio and 95% confidence interval for pyogenic liver abscesses associated with herpes zoster and other comorbidities. The overall incidence rate was 1.38-fold higher in the herpes zoster group than in the non-herpes zoster group (4.47 vs. 3.25 per 10000 person-years, 95% confidence interval 1.32, 1.44). After controlling for potential confounding factors, the adjusted hazard ratio of pyogenic liver abscesses was 1.34 in the herpes zoster group (95% confidence interval 1.05, 1.72) when compared with the non-herpes zoster group. Sex (in this case male), age, presence of biliary stones, chronic kidney diseases, chronic liver diseases, cancers, and diabetes mellitus were also significantly associated with pyogenic liver abscesses. Patients with herpes zoster are associated with an increased hazard of developing pyogenic liver abscesses.

Varicella Zoster Virus and Large Vessel Vasculitis, the Absence of an Association.

PubMed

Procop, Gary W; Eng, Charis; Clifford, Alison; Villa-Forte, Alexandra; Calabrese, Leonard H; Roselli, Eric; Svensson, Lars; Johnston, Douglas; Pettersson, Gosta; Soltesz, Edward; Lystad, Lisa; Perry, Julian D; Blandford, Alexander; Wilson, Deborah A; Hoffman, Gary S

2017-01-01

It is controversial whether microorganisms play a role in the pathogenesis of large and medium vessel vasculitides (eg, giant cell arteritis [GCA], Takayasu arteritis [TAK] and focal idiopathic aortitis [FIA]). Recent studies have reported the presence of Varicella Zoster Virus (VZV) within formalin-fixed, paraffin-embedded temporal arteries and aortas of about three-quarters or more of patients with these conditions, and in a minority of controls. In a prospective study, we sought to confirm these findings using DNA extracted from vessels that were harvested under surgically aseptic conditions and snap frozen. DNA samples extracted from 11 surgically sterile temporal arteries and 31 surgically sterile thoracic aortas were used in an attempt to identify the vessel-associated VZV genome. Two different validated PCR methods were used. Thirty-one thoracic aorta aneurysm specimens included biopsies from 8 patients with GCA, 2 from patients with TAK, 6 from patients with FIA, and 15 from patients without vasculitis, who had non-inflammatory aneurysms. Eleven temporal artery biopsies were collected from 5 patients with GCA and 6 controls. The presence of VZV was not identified in either the specimens from patients with large vessel vasculitis or from the controls. Using surgically sterile snap-frozen specimens, we were unable to confirm recent reports of the presence of VZV in either aortas or temporal arteries from patients with large vessel vasculitis or controls.

A model of lytic, latent, and reactivating varicella-zoster virus infections in isolated enteric neurons.

PubMed

Gershon, Anne A; Chen, Jason; Gershon, Michael D

2008-03-01

Because human primary afferent neurons are not readily obtained, we sought to develop a model in which the lytic, latent, and reactivating phases of varicella-zoster virus (VZV) infection were recapitulated in neurons from an animal source. Enteric neurons were obtained from the small intestine of adult guinea pigs and from the bowel of fetal mice. Latency was established when these neurons were infected by cell-free VZV in the absence of fibroblasts or other cells of mesodermal origin. In contrast, lytic infection ensued when fibroblasts were present or when the enteric neurons were infected by cell-associated VZV. Latency was associated with the expression of a limited subset of viral genes, the products of which were restricted to the cytoplasm. Lysis was associated with the expression of viral glycoproteins, nuclear translocation of latency-associated gene products, and rapid cell death. Reactivation was accomplished by expressing VZV open reading frame (ORF) 61p or herpes simplex virus ICP0 in latently infected neurons. Isolated enteric neurons from guinea pigs and mice recapitulate latent gene expression in human cranial nerve and dorsal root ganglia. Expression of latency-associated VZV gene products was detected in 88% of samples of adult human intestine, suggesting that VZV not only infects enteric neurons but also is latent in the human enteric nervous system. This in vitro model should facilitate further understanding of latency and reactivation of VZV.

Three year seroepidemiological study of varicella-zoster virus in São Paulo, Brazil.

PubMed

Yu, A L; Costa, J M; Amaku, M; Pannuti, C S; Souza, V A; Zanetta, D M; Burattini, M N; Massad, E; Azevedo, R S

2000-01-01

A serosurvey of varicella has been carried out in children attending the public school network of São Paulo city, Brazil, from 1992 to 1994. This study was performed in order to establish the age related prevalence of antibodies against varicella-zoster virus (VZV) and its age specific transmission dynamics pattern in these children. Among 2500 schools in the city of São Paulo public network, 304 were randomly selected; 7 children of a given age (ranging from 1 to 15 years) were randomly selected in each school, and blood samples were obtained by fingerprick into filter paper. Blood eluates were analyzed for the presence of antibodies to VZV by ELISA. Proportion of seropositivity were calculated for each age group. Samples consisted of 1768 individuals in 1992, 1758 in 1993, and 1817 in 1994, resulting in 5343 eluates. A high proportion of seropositive children from 1 to 3 years of age was observed, ascending until 10 years of age and reaching a plateau around 90% afterwards. VZV transmission in this community was similar along the three years of the study. In children attending public schools in the city of São Paulo, contact with VZV occurs in early childhood. If immunization against VZV is considered it should be introduced as soon as possible.

Shingles (herpes zoster) vaccine (zostavax(®)): a review of its use in the prevention of herpes zoster and postherpetic neuralgia in adults aged ≥50 years.

PubMed

Keating, Gillian M

2013-07-01

The live, attenuated shingles (herpes zoster) vaccine Zostavax(®) is approved in the EU for use in the prevention of herpes zoster and postherpetic neuralgia in adults aged ≥50 years. In adults aged ≥60 years, zoster vaccine reduced the burden of illness associated with herpes zoster, with reductions in the incidence of postherpetic neuralgia and herpes zoster, according to the results of the Shingles Prevention Study. Results of subsequent Short- and Long-Term Persistence Substudies indicate that the efficacy of zoster vaccine is maintained in the longer term, albeit with a gradual decline over time. In the Zostavax Efficacy and Safety Trial, zoster vaccine reduced the incidence of herpes zoster in adults aged 50-59 years. Findings of these studies are supported by the results of large, retrospective, cohort studies. Zoster vaccine was generally well tolerated, with injection-site adverse events being the most commonly reported adverse events. In conclusion, zoster vaccine provides an important opportunity to reduce the burden of illness associated with herpes zoster by reducing the incidence of herpes zoster and postherpetic neuralgia.

[Results of acyclovir treatment of chickenpox and herpes zoster in children with immune tolerance].

PubMed

Jankowska, H; Szczepańska-Putz, M; Wojnarowski, M

Acyclovir was used for the treatment of Varicella-zoster virus infections in 53 children (10 neonates and 43 children aged between 2 an 15 years) with immunological system deficiency hospitalized at the Department of the Infectious Diseases of Childhood in the Medical Academy in Warszawa. The obtained results of therapy were favourable except one fatal case of the child with visceral dissemination of the virus prior to acyclovir treatment. Compared with other antiviral agents used by the authors previously, acyclovir proved to be the most effective.

Herpes Zoster Optic Neuropathy.

PubMed

Kaufman, Aaron R; Myers, Eileen M; Moster, Mark L; Stanley, Jordan; Kline, Lanning B; Golnik, Karl C

2018-06-01

Herpes zoster optic neuropathy (HZON) is a rare manifestation of herpes zoster ophthalmicus (HZO). The aim of our study was to better characterize the clinical features, therapeutic choices, and visual outcomes in HZON. A retrospective chart review was performed at multiple academic eye centers with the inclusion criteria of all eyes presenting with optic neuropathy within 1 month of cutaneous zoster of the ipsilateral trigeminal dermatome. Data were collected regarding presenting features, treatment regimen, and visual acuity outcomes. Six patients meeting the HZON inclusion criteria were identified. Mean follow-up was 2.75 months (range 0.5-4 months). Herpes zoster optic neuropathy developed at a mean of 14.1 days after initial rash (range 6-30 days). Optic neuropathy was anterior in 2 eyes and retrobulbar in 4 eyes. Other manifestations of HZO included keratoconjunctivitis (3 eyes) and iritis (4 eyes). All patients were treated with systemic antiviral therapy in addition to topical and/or systemic corticosteroids. At the last follow-up, visual acuity in 3 eyes had improved relative to presentation, 2 eyes had worsened, and 1 eye remained the same. The 2 eyes that did not receive systemic corticosteroids had the best observed final visual acuity. Herpes zoster optic neuropathy is an unusual but distinctive complication of HZO. Visual recovery after HZON is variable. Identification of an optimal treatment regiment for HZON could not be identified from our patient cohort. Systemic antiviral agents are a component of HZON treatment regimens. Efficacy of systemic corticosteroids for HZON remains unclear and should be considered on a case-by-case basis.

Vaccine-strain herpes zoster found in the trigeminal nerve area in a healthy child: A case report.

PubMed

Iwasaki, Sayaka; Motokura, Kouji; Honda, Yoshitaka; Mikami, Masamitsu; Hata, Daisuke; Hata, Atsuko

2016-12-01

A previously healthy 2-year-old girl, vaccinated for varicella at 17 months, was admitted because of left-sided facial herpes zoster caused by vaccine-strain varicella-zoster virus (VZV). She recovered fully with no complication after intravenous treatment using acyclovir. Earlier reports have described that herpes zoster (HZ) rashes caused by vaccine-strain VZV tend to occur on the dermis corresponding to the skin area where the varicella vaccine was received. However, rashes appeared on this girl only in the trigeminal nerve area, which is unrelated to the vaccinated site. Results underscore the importance of distinguishing vaccine-strain VZV from wild-type VZV whenever encountering HZ cases after vaccination, even in immunocompetent children, irrespective of the skin lesion site. Monitoring vaccine-strain HZ incidence rates is expected to elucidate many aspects of varicella vaccine safety. Copyright © 2016 Elsevier B.V. All rights reserved.

Herpes zoster and vaccination: a clinical review.

PubMed

Adams, Erin N; Parnapy, Sarah; Bautista, Philip

2010-05-01

Herpes zoster, herpes zoster vaccine, and the cost-effectiveness of the vaccine are reviewed. Herpes zoster infection is estimated to affect one in three people during their lifetime. Two thirds of people who develop this disease are over age 60 years. Postherpetic neuralgia (PHN) is the most common complication of herpes zoster, occurring in 10-18% of patients. The associated chronic pain can be very debilitating, affecting patients' quality of life. The pain may last for months or years and is difficult to treat, leading to increased health care costs and morbidity. To prevent herpes zoster, a live attenuated vaccine was developed and approved for marketing in 2006 for individuals age > or = 60 years. The safety and efficacy of the vaccine were evaluated in the Shingles Prevention Study in 38,546 adults age > or = 60 years. Compared with placebo, administration of the vaccine resulted in a 51.3% reduction in the incidence of herpes zoster and a 66.5% reduction in the incidence of PHN (p < 0.001 for both comparisons). A single dose of the vaccine is approximately $162 and is not covered by all insurance plans. Several studies evaluated the cost-effectiveness of the vaccine, which was found to be most beneficial in individuals age 70 years or older. The use of the vaccine appears to reduce health care costs and protect the public health. The herpes zoster vaccine is effective in preventing herpes zoster and decreasing the incidence of complications. However, insurance coverage may hinder eligible patients from receiving the vaccination.

Effects of Shield1 on the viral replication of varicella-zoster virus containing FKBP-tagged ORF4 and 48

PubMed Central

Li, Shuying; Liu, Zhanjun; Li, Ji; Liu, Aihua; Zhu, Lihua; Yu, Kui; Zhang, Ke

2018-01-01

The present study aimed to explore the effects of a stabilizing ligand, Shield-1, on the replication of recombinant varicella-zoster virus (VZV) containing FK506 binding protein (FKPB) tags in essential open reading frames (ORF) 4 and 48. A specific galactokinase (galK) selection method was conducted, following the addition of galK labels to VZV ORF4 and 48, using a SW102 VZV bacterial artificial chromosome (BAC) system. Subsequently, recombinant VZV containing FKPB tags in ORF4 and 48 was constructed by counterselection and homologous recombination. Recombinant viral plasmids containing FKPB-tagged VZV ORF4 and 48 were extracted and transfected into human acute retinal pigment epithelial ARPE-19 cells. The results demonstrated that the FKPB-tagged viral protein was rapidly degraded by proteases in recombinant virus-infected ARPE-19 cells. In addition, the recombinant VZVORF4-FKBP-ORF48-FKBP virus could not grow if a synthetic ligand of FKBP, Shield1, was not added to the ARPE-19 cell culture medium; however, the degradation of FKPB-tagged viral protein was prevented if Shield1 was added to the ARPE-19 cell culture medium, thereby allowing viral replication in ARPE-19 cells. These results indicated that Shield1 may regulate replication of recombinant VZVORF4-FKBP-ORF48-FKBP following transfection into human epithelial cells. PMID:29115621

Network biology discovers pathogen contact points in host protein-protein interactomes.

PubMed

Ahmed, Hadia; Howton, T C; Sun, Yali; Weinberger, Natascha; Belkhadir, Youssef; Mukhtar, M Shahid

2018-06-13

In all organisms, major biological processes are controlled by complex protein-protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1 MAIN ). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1 MAIN and are preferential targets of pathogen effectors. We extend these network-centric analyses to Cell Surface Interactome (CSI LRR ) and predict its 35 most influential nodes. To determine their biological relevance, we show that these proteins physically interact with pathogen effectors and modulate plant immunity. Overall, our findings contrast with centrality-lethality rule, discover fast information spreading nodes, and highlight the structural properties of pathogen targets in two different interactomes. Finally, this theoretical framework could possibly be applicable to other inter-species interactomes to reveal pathogen contact points.

A TRPV2 interactome-based signature for prognosis in glioblastoma patients.

PubMed

Doñate-Macián, Pau; Gómez, Antonio; Dégano, Irene R; Perálvarez-Marín, Alex

2018-04-06

Proteomics aids to the discovery and expansion of protein-protein interaction networks, which are key to understand molecular mechanisms in physiology and physiopathology, but also to infer protein function in a guilt-by-association fashion. In this study we use a systematic protein-protein interaction membrane yeast two-hybrid method to expand the interactome of TRPV2, a cation channel related to nervous system development. After validation of the interactome in silico , we define a TRPV2-interactome signature combining proteomics with the available physio-pathological data in Disgenet to find interactome-disease associations, highlighting nervous system disorders and neoplasms. The TRPV2-interactome signature against available experimental data is capable of discriminating overall risk in glioblastoma multiforme prognosis, progression, recurrence, and chemotherapy resistance. Beyond the impact on glioblastoma physiopathology, this study shows that combining systematic proteomics with in silico methods and available experimental data is key to open new perspectives to define novel biomarkers for diagnosis, prognosis and therapeutics in disease.

A TRPV2 interactome-based signature for prognosis in glioblastoma patients

PubMed Central

Dégano, Irene R.; Perálvarez-Marín, Alex

2018-01-01

Proteomics aids to the discovery and expansion of protein-protein interaction networks, which are key to understand molecular mechanisms in physiology and physiopathology, but also to infer protein function in a guilt-by-association fashion. In this study we use a systematic protein-protein interaction membrane yeast two-hybrid method to expand the interactome of TRPV2, a cation channel related to nervous system development. After validation of the interactome in silico, we define a TRPV2-interactome signature combining proteomics with the available physio-pathological data in Disgenet to find interactome-disease associations, highlighting nervous system disorders and neoplasms. The TRPV2-interactome signature against available experimental data is capable of discriminating overall risk in glioblastoma multiforme prognosis, progression, recurrence, and chemotherapy resistance. Beyond the impact on glioblastoma physiopathology, this study shows that combining systematic proteomics with in silico methods and available experimental data is key to open new perspectives to define novel biomarkers for diagnosis, prognosis and therapeutics in disease. PMID:29719613

Seroepidemiologic Survey of Varicella-Zoster Virus in Korean Adults Using Glycoprotein Enzyme Immuno Assay and Fluorescent Antibody to Membrane Antigen Test

PubMed Central

Kim, Yun Hwa; Hwang, Ji Young; Lee, Kyung Min; Choi, Jin Hee; Lee, Tae Yoon; Choi, Jong Soo

2011-01-01

Background Herpes zoster (HZ) occurs mainly in the elderly and Korea is rapidly becoming an aging society. Therefore, it is important to know the immune status against varicella-zoster virus (VZV) in Korean adults to prevent the disease. Objective The aim of this study was to survey the immune status of Korean adults over 40 years of age against VZV. Methods Antibody titer was measured using a VaccZyme™ VZV glycoprotein enzyme immunoassay (gpEIA) (Binding Site, UK). Fluorescent antibody to membrane antigen (FAMA) test was performed to measure the seropositive rate. Results HZ incidence in the 214 adults enrolled in this study was 10.3%. The gpEIA geometric mean titer (GMT) was 490 mIU/ml and 90.2% of the subjects had a protective level of gpEIA antibody titer against varicella. The average gpEIA GMT of adults who previously had HZ was 1,122 mIU/ml, which was higher than the average gpEIA GMT of 457 mIU/ml in adults who had not had HZ. The FAMA positive rate was 98.6%. Conclusion Most (90.2%) Korean adults ≥40-years-of-age have a protective level of gpEIA antibody against varicella and 98.6% were FAMA seropositive. The GMT of gpEIA antibody was significantly increased with age, and was higher in adults with a history of HZ. PMID:21738361

CASTIN: a system for comprehensive analysis of cancer-stromal interactome.

PubMed

Komura, Daisuke; Isagawa, Takayuki; Kishi, Kazuki; Suzuki, Ryohei; Sato, Reiko; Tanaka, Mariko; Katoh, Hiroto; Yamamoto, Shogo; Tatsuno, Kenji; Fukayama, Masashi; Aburatani, Hiroyuki; Ishikawa, Shumpei

2016-11-09

Cancer microenvironment plays a vital role in cancer development and progression, and cancer-stromal interactions have been recognized as important targets for cancer therapy. However, identifying relevant and druggable cancer-stromal interactions is challenging due to the lack of quantitative methods to analyze whole cancer-stromal interactome. We present CASTIN (CAncer-STromal INteractome analysis), a novel framework for the evaluation of cancer-stromal interactome from RNA-Seq data using cancer xenograft models. For each ligand-receptor interaction which is derived from curated protein-protein interaction database, CASTIN summarizes gene expression profiles of cancer and stroma into three evaluation indices. These indices provide quantitative evaluation and comprehensive visualization of interactome, and thus enable to identify critical cancer-microenvironment interactions, which would be potential drug targets. We applied CASTIN to the dataset of pancreas ductal adenocarcinoma, and successfully characterized the individual cancer in terms of cancer-stromal relationships, and identified both well-known and less-characterized druggable interactions. CASTIN provides comprehensive view of cancer-stromal interactome and is useful to identify critical interactions which may serve as potential drug targets in cancer-microenvironment. CASTIN is available at: http://github.com/tmd-gpat/CASTIN .

Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults.

PubMed

Lal, Himal; Cunningham, Anthony L; Godeaux, Olivier; Chlibek, Roman; Diez-Domingo, Javier; Hwang, Shinn-Jang; Levin, Myron J; McElhaney, Janet E; Poder, Airi; Puig-Barberà, Joan; Vesikari, Timo; Watanabe, Daisuke; Weckx, Lily; Zahaf, Toufik; Heineman, Thomas C

2015-05-28

In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response. We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults. A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups. The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).

Mutations in RNA Polymerase III genes and defective DNA sensing in adults with varicella-zoster virus CNS infection.

PubMed

Carter-Timofte, Madalina E; Hansen, Anders F; Christiansen, Mette; Paludan, Søren R; Mogensen, Trine H

2018-05-01

Recently, deficiency in the cytosolic DNA sensor RNA Polymerase III was described in children with severe primary varicella-zoster virus (VZV) infection in the CNS and lungs. In the present study we examined adult patients with VZV CNS infection caused by viral reactivation. By whole exome sequencing we identified mutations in POL III genes in two of eight patients. These mutations were located in the coding regions of the subunits POLR3A and POLR3E. In functional assays, we found impaired expression of antiviral and inflammatory cytokines in response to the POL III agonist Poly(dA:dT) as well as increased viral replication in patient cells compared to controls. Altogether, this study provides significant extension on the current knowledge on susceptibility to VZV infection by demonstrating mutations in POL III genes associated with impaired immunological sensing of AT-rich DNA in adult patients with VZV CNS infection.

Latent virus reactivation in astronauts on the international space station.

PubMed

Mehta, Satish K; Laudenslager, Mark L; Stowe, Raymond P; Crucian, Brian E; Feiveson, Alan H; Sams, Clarence F; Pierson, Duane L

2017-01-01

Reactivation of latent herpes viruses was measured in 23 astronauts (18 male and 5 female) before, during, and after long-duration (up to 180 days) spaceflight onboard the international space station . Twenty age-matched and sex-matched healthy ground-based subjects were included as a control group. Blood, urine, and saliva samples were collected before, during, and after spaceflight. Saliva was analyzed for Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus type 1. Urine was analyzed for cytomegalovirus. One astronaut did not shed any targeted virus in samples collected during the three mission phases. Shedding of Epstein-Barr virus, varicella-zoster virus, and cytomegalovirus was detected in 8 of the 23 astronauts. These viruses reactivated independently of each other. Reactivation of Epstein-Barr virus, varicella-zoster virus, and cytomegalovirus increased in frequency, duration, and amplitude (viral copy numbers) when compared to short duration (10 to 16 days) space shuttle missions. No evidence of reactivation of herpes simplex virus type 1, herpes simplex virus type 2, or human herpes virus 6 was found. The mean diurnal trajectory of salivary cortisol changed significantly during flight as compared to before flight ( P  = 0.010). There was no statistically significant difference in levels of plasma cortisol or dehydoepiandosterone concentrations among time points before, during, and after flight for these international space station crew members, although observed cortisol levels were lower at the mid and late-flight time points. The data confirm that astronauts undertaking long-duration spaceflight experience both increased latent viral reactivation and changes in diurnal trajectory of salivary cortisol concentrations.

Demonstration of NK cell-mediated lysis of varicella-zoster virus (VZV)-infected cells: characterization of the effector cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilden, A.B.; Cauda, R.; Grossi, C.E.

1986-06-01

Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of /sup 51/Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a/sup +/ Leu-4/sup -/ granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar tomore » those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of /sup 51/Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.« less

Herpes Zoster and Postherpetic Neuralgia: Practical Consideration for Prevention and Treatment

PubMed Central

2015-01-01

Herpes zoster (HZ) is a transient disease caused by the reactivation of latent varicella zoster virus (VZV) in spinal or cranial sensory ganglia. It is characterized by a painful rash in the affected dermatome. Postherpetic neuralgia (PHN) is the most troublesome side effect associated with HZ. However, PHN is often resistant to current analgesic treatments such as antidepressants, anticonvulsants, opioids, and topical agents including lidocaine patches and capsaicin cream and can persist for several years. The risk factors for reactivation of HZ include advanced age and compromised cell-mediated immunity (CMI). Early diagnosis and treatment with antiviral agents plus intervention treatments is believed to shorten the duration and severity of acute HZ and reduce the risk of PHN. Prophylactic vaccination against VZV can be the best option to prevent or reduce the incidence of HZ and PHN. This review focuses on the pathophysiology, clinical features, and management of HZ and PHN, as well as the efficacy of the HZ vaccine. PMID:26175877

Simultaneous detection of and differentiation between herpes simplex and varicella-zoster viruses with two fluorescent probes in the same test system.

PubMed

Brumback, B G; Farthing, P G; Castellino, S N

1993-12-01

Specimens from skin lesions were examined simultaneously for herpes simplex virus (HSV) and varicella-zoster virus (VZV) by direct specimen testing and shell vial culture in single-test systems. For direct testing, cells in a single specimen well were stained with a combination direct-indirect immunofluorescence stain by using two fluorescent tags. A total of 203 fresh specimens were tested in parallel. Of these, 100 specimens contained too few cells for the direct VZV comparison and 91 contained too few cells for the HSV comparison. After these specimens were eliminated, the sensitivities and specificities, respectively, of the dual direct test were 86.1 and 97.3% for HSV compared with single culture and 92.2 and 100% for VZV compared with single direct testing. Shell vial monolayers in the combined cultures were stained for both viruses by the same method. A total of 305 fresh specimens were cultured in parallel by dual- and single-culture methods. The sensitivities and specificities, respectively, of the combined culture compared with separate cultures were 100 and 98.4% for HSV and 87.9 and 99.2% for VZV. The combined methods gave a performance comparable to those of single tests, required less specimen volume, and were less costly to perform.

The health and economic burden of chickenpox and herpes zoster in Belgium.

PubMed

Bilcke, J; Ogunjimi, B; Marais, C; de Smet, F; Callens, M; Callaert, K; van Kerschaver, E; Ramet, J; van Damme, P; Beutels, P

2012-11-01

Varicella-zoster virus causes chickenpox (CP) and after reactivation herpes zoster (HZ). Vaccines are available against both diseases warranting an assessment of the pre-vaccination burden of disease. We collected data from relevant Belgian databases and performed five surveys of CP and HZ patients. The rates at which a general practitioner is visited at least once for CP and HZ are 346 and 378/100 000 person-years, respectively. The average CP and HZ hospitalization rates are 5·3 and 14·2/100 000 person-years respectively. The direct medical cost for HZ is about twice as large as the direct medical cost for CP. The quality-adjusted life years lost for ambulatory CP patients consulting a physician is more than double that of those not consulting a physician (0·010 vs. 0·004). In conclusion, both diseases cause a substantial burden in Belgium.

Incidence and use of resources for chickenpox and herpes zoster in Latin America and the Caribbean--a systematic review and meta-analysis.

PubMed

Bardach, Ariel; Cafferata, María Luisa; Klein, Karen; Cormick, Gabriela; Gibbons, Luz; Ruvinsky, Silvina

2012-12-01

Varicella-zoster virus causes chickenpox and herpes zoster. More than 90% of varicella cases occur in childhood. The aim of this study was to gather all relevant information on epidemiology and resource use in Latin America and the Caribbean since 2000. Epidemiologic studies published since 2000 with at least 50 cases of varicella or herpes zoster, or at least 10 cases of congenital disease were included. Gray literature was also searched. Outcomes included incidence, admission rate, mortality and case-fatality ratio. Use of resources and both direct and indirect costs associated were extracted. From the 495 records identified, 23 were included in the meta-analysis to report varicella-zoster virus outcomes and 3 in the herpes zoster analysis. The global pooled varicella incidence in subjects under 15 years of age was 42.9 cases per 1000 individuals per year (95% confidence interval: 26.9-58.9); children under 5 years of age were the most affected. Pooled general admission rate was 3.5 per 100,000 population (95% confidence interval: 2.9-4.1) and median hospitalization was 5-9 days. The most common varicella complications reported in studies were skin infections (3-61%), followed by respiratory infections (0-15%) and neurologic problems (1-5%). Direct costs averaged (2011/international dollar [I$]) $2040 per admission (range, I$ 298-5369) and I$70 per clinical visit (range, 11-188 I$). Limited information was available on the outcomes studied. Improvements in the surveillance of ambulatory cases are required to obtain a better epidemiologic picture. As of 2011, only 2 countries introduced the vaccine in national immunization programs in Latin America and the Caribbean.

Varicella Zoster Virus and Large Vessel Vasculitis, the Absence of an Association

PubMed Central

Procop, Gary W.; Eng, Charis; Clifford, Alison; Villa-Forte, Alexandra; Calabrese, Leonard H.; Roselli, Eric; Svensson, Lars; Johnston, Douglas; Pettersson, Gosta; Soltesz, Edward; Lystad, Lisa; Perry, Julian D.; Blandford, Alexander; Wilson, Deborah A.; Hoffman, Gary S.

2017-01-01

Objective It is controversial whether microorganisms play a role in the pathogenesis of large and medium vessel vasculitides (eg, giant cell arteritis [GCA], Takayasu arteritis [TAK] and focal idiopathic aortitis [FIA]). Recent studies have reported the presence of Varicella Zoster Virus (VZV) within formalin-fixed, paraffin-embedded temporal arteries and aortas of about three-quarters or more of patients with these conditions, and in a minority of controls. In a prospective study, we sought to confirm these findings using DNA extracted from vessels that were harvested under surgically aseptic conditions and snap frozen. Methods and Results DNA samples extracted from 11 surgically sterile temporal arteries and 31 surgically sterile thoracic aortas were used in an attempt to identify the vessel-associated VZV genome. Two different validated PCR methods were used. Thirty-one thoracic aorta aneurysm specimens included biopsies from 8 patients with GCA, 2 from patients with TAK, 6 from patients with FIA, and 15 from patients without vasculitis, who had non-inflammatory aneurysms. Eleven temporal artery biopsies were collected from 5 patients with GCA and 6 controls. The presence of VZV was not identified in either the specimens from patients with large vessel vasculitis or from the controls. Conclusions Using surgically sterile snap-frozen specimens, we were unable to confirm recent reports of the presence of VZV in either aortas or temporal arteries from patients with large vessel vasculitis or controls. PMID:28758156

Evaluation of efficacy and effectiveness of live attenuated zoster vaccine.

PubMed

Gabutti, G; Valente, N; Sulcaj, N; Stefanati, A

2014-12-01

Herpes zoster (HZ) is a viral disease characterized by a dermatologic and neurologic involvement caused by the reactivation of the latent varicella zoster virus (VZV) acquired during primary infection (varicella). HZ incidence increases with age and is related to waning specific cell-mediated immunity (CMI). The most frequent complication of HZ is post-herpetic neuralgia (PHN) characterized by chronic pain lasting at least 30 days, with impact on patients' quality of life. Available treatments are quite unsatisfactory in reducing pain and length of the disease. The evaluation of the epidemiology, the debilitating complications (PHN), the suboptimal available treatments and the costs related to the diagnosis and clinical/therapeutic management of HZ patients have been the rationale for the search of an adequate preventive measure against this disease. The target of this intervention is to reduce the frequency and severity of HZ and related complications by stimulating CMI. Prevention has recently become possible with the live attenuated vaccine Oka/Merck, with an antigen content at least 10-fold higher than the antigen content of pediatric varicella vaccines. Clinical studies show a good level of efficacy and effectiveness, particularly against the burden of illness and PHN in all age classes. Accordingly to the summary of the characteristics of the product the zoster vaccine is indicated for the prevention of HZ and PHN in individuals 50 years of age or older and is effective and safe in subjects with a positive history of HZ.

Complications of varicella zoster.

PubMed

Gücüyener, Kivilcim; Citak, Elvan Cağlar; Elli, Murat; Serdaroğlu, Ayse; Citak, Funda Erkasar

2002-02-01

Primary infection with varicella zoster is characterzed by a generalized vesicular rash usually without significant systemic illness. Encephalitis, pneumonitis, pancreatitis, nephritis, Reye and Guillan-Barre syndrome transvers myelitis, myocarditis have been reported before, but there is not any case having all these system to be involved during the same infection in a sequential manner ending up with multiorgan failure. We wanted to represent 21-month-old boy had a multiorgan failure due to varicella zoster infection.

Exploring the Human-Nipah Virus Protein-Protein Interactome

PubMed Central

Vera-Velasco, Natalia M.; Mingarro, Ismael

2017-01-01

ABSTRACT Nipah virus is an emerging, highly pathogenic, zoonotic virus of the Paramyxoviridae family. Human transmission occurs by close contact with infected animals, the consumption of contaminated food, or, occasionally, via other infected individuals. Currently, we lack therapeutic or prophylactic treatments for Nipah virus. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. This aim led us to perform the present work, in which we identified 101 human-Nipah virus protein-protein interactions (PPIs), most of which (88) are novel. This data set provides a comprehensive view of the host complexes that are manipulated by viral proteins. Host targets include the PRP19 complex and the microRNA (miRNA) processing machinery. Furthermore, we explored the biologic consequences of the interaction with the PRP19 complex and found that the Nipah virus W protein is capable of altering p53 control and gene expression. We anticipate that these data will help in guiding the development of novel interventional strategies to counter this emerging viral threat. IMPORTANCE Nipah virus is a recently discovered virus that infects a wide range of mammals, including humans. Since its discovery there have been yearly outbreaks, and in some of them the mortality rate has reached 100% of the confirmed cases. However, the study of Nipah virus has been largely neglected, and currently we lack treatments for this infection. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. In the present work, we identified 101 human-Nipah virus protein-protein interactions using an affinity purification approach coupled with mass spectrometry. Additionally, we explored the cellular consequences of some of these interactions. Globally, this data set offers a comprehensive and detailed view of the host machinery's contribution to the Nipah virus

Exploring the Human-Nipah Virus Protein-Protein Interactome.

PubMed

Martinez-Gil, Luis; Vera-Velasco, Natalia M; Mingarro, Ismael

2017-12-01

Nipah virus is an emerging, highly pathogenic, zoonotic virus of the Paramyxoviridae family. Human transmission occurs by close contact with infected animals, the consumption of contaminated food, or, occasionally, via other infected individuals. Currently, we lack therapeutic or prophylactic treatments for Nipah virus. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. This aim led us to perform the present work, in which we identified 101 human-Nipah virus protein-protein interactions (PPIs), most of which (88) are novel. This data set provides a comprehensive view of the host complexes that are manipulated by viral proteins. Host targets include the PRP19 complex and the microRNA (miRNA) processing machinery. Furthermore, we explored the biologic consequences of the interaction with the PRP19 complex and found that the Nipah virus W protein is capable of altering p53 control and gene expression. We anticipate that these data will help in guiding the development of novel interventional strategies to counter this emerging viral threat. IMPORTANCE Nipah virus is a recently discovered virus that infects a wide range of mammals, including humans. Since its discovery there have been yearly outbreaks, and in some of them the mortality rate has reached 100% of the confirmed cases. However, the study of Nipah virus has been largely neglected, and currently we lack treatments for this infection. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. In the present work, we identified 101 human-Nipah virus protein-protein interactions using an affinity purification approach coupled with mass spectrometry. Additionally, we explored the cellular consequences of some of these interactions. Globally, this data set offers a comprehensive and detailed view of the host machinery's contribution to the Nipah virus's life cycle

[Seroprevalence of varicella-zoster virus in children with cancer in six hospitals in Santiago, Chile].

PubMed

Izquierdo, Giannina; Zubieta, Marcela; Martínez G, María J; Alvarez, Ana M; Aviles, Carmen L; Becker, Ana; Peña, Mónica; Salgado, Carmen; Silva, Pamela; Topelberg, Santiago; Tordecilla, Juan; Varas, Mónica; Villarroel, Milena; Viviani, Tamara; Santolaya, María E

2012-12-01

Infections with varicella-zoster virus (VVZ) in immunocompromised children imply a high mortality. There is no data about VVZ seroprevalence in children with cancer in our country. To determine the prevalence of VVZ antibodies in children with cancer who have undergone chemotherapy or have undergone a hematopoietic stem cell transplant. collaborative, multicenter study. Serum samples were collected from 281 children with cancer and episodes of febrile neutropenia from 6 hospitals belonging to the public health network in the Metropolitan Region between June 2004 and August 2006. These samples were stored at -70 ° C, and 200 of them were randomly chosen and analyzed to determine VVZ IgG (ELISA). 179 samples from 179 children, 65% male. Ninety eighth/179 (55%) were positive, 72/179 (40%) negative and 9/179 (5%) indeterminate. Stratified by age, seropositive percentage was: 1 to 4 years 32%, 5-9 years 42%, 10-14 years 78%, over 15 years 88%. Forty percent of children treated for cancer are seronegative to VVZ infection, a frequency that decreases with age. These results support the adoption of preventive measures to avoid infection in this population of children at risk of developing a serious and possibly fatal illness.

Type I interferon inhibits varicella-zoster virus replication by interfering with the dynamic interaction between mediator and IE62 within replication compartments.

PubMed

Ku, Chia-Chi; Chang, Yi-Hsuan; Chien, Yun; Lee, Tsung-Lin

2016-01-01

Varicella-zoster virus (VZV) is the causative agent of varicella and zoster. The immediate-early protein, IE62 is the predominant VZ virion tegument protein, transactivating the expression of all kinetic classes of VZV genes. IE62 is localized to punctae that form DNA replication compartments in the nuclei of VZV infected cells. The morphological changes and the increase in the size of replication compartments that express IE62 are correlated with production of VZ virions. Mammalian Mediator serves as a coactivator of IE62 and functions by bridging DNA-binding transcription factors¸ RNA polymerase II (RNAP II) and their target DNAs for VZV replication. While VZV is highly sensitive to type I interferons (IFNs), how IFN-α inhibits early events during VZV replication is poorly understood. In this study, we performed in situ analysis to investigate the effects of IFN-α on the dynamic interactions of IE62 with the Mediator MED25 subunit and the RNAP II negative regulator cycle-dependent kinase 8 (CDK8) in VZV infected cells by confocal immunofluorescence. We found that in addition to dose-dependent inhibition of the yields of infectious virus by IFN treatment, IFN-α prominently impeded the development of large IE62(+) nuclear compartments and significantly decreased transcription of VZV genes. Both the expression level and stable recruitment of MED25 to IE62(+) replication compartments were inhibited by IFN-α. While IFN-α treatment upregulated CDK8 expression, redistribution and recruitment of CDK8 to IE62(+) replication compartments in infected cells was not affected by VZV. IFN-α exerts multiple inhibitory activities against virus infections. In this study, we provide visionary demonstration that continuous translocation of MED25 into VZV replication compartments ensures production of virions. IFN-α greatly impedes the formation of a stable complex between IE62 and the Mediator complex thereby suppresses VZV gene transcription. Our demonstration that IFN

Characterization of a Protein Interactome by Co-Immunoprecipitation and Shotgun Mass Spectrometry.

PubMed

Maccarrone, Giuseppina; Bonfiglio, Juan Jose; Silberstein, Susana; Turck, Christoph W; Martins-de-Souza, Daniel

2017-01-01

Identifying the partners of a given protein (the interactome) may provide leads about the protein's function and the molecular mechanisms in which it is involved. One of the alternative strategies used to characterize protein interactomes consists of co-immunoprecipitation (co-IP) followed by shotgun mass spectrometry. This enables the isolation and identification of a protein target in its native state and its interactome from cells or tissue lysates under physiological conditions. In this chapter, we describe a co-IP protocol for interactome studies that uses an antibody against a protein of interest bound to protein A/G plus agarose beads to isolate a protein complex. The interacting proteins may be further fractionated by SDS-PAGE, followed by in-gel tryptic digestion and nano liquid chromatography high-resolution tandem mass spectrometry (nLC ESI-MS/MS) for identification purposes. The computational tools, strategy for protein identification, and use of interactome databases also will be described.

[Seroprevalence of rubella virus, varicella zoster virus, cytomegalovirus and parvovirus B19 among pregnant women in the Sousse region, Tunisia].

PubMed

Hannachi, N; Marzouk, M; Harrabi, I; Ferjani, A; Ksouri, Z; Ghannem, H; Khairi, H; Hidar, S; Boukadida, J

2011-02-01

The aim of the study is to evaluate seroprevalence of rubella virus (RV), cytomegalovirus (CMV), varicella zoster virus (VZV), and parvovirus B19 (PB19) in 404 Tunisian pregnant women, and to determine reliability of maternal past history of eruption. Sociodemographic characteristics, risk factors, and past history of eruption were collected through a questionnaire. Serologic tests were performed using enzyme immunoassays. Risk factors were analyzed using univariate and multivariate logistic regression models. Seroprevalences were 79.7% for rubella, 96.3% for CMV, 80.9% for VZV, and 76.2% for PB19. In multivariate analysis, the number of persons per room (> 2) in the house during childhood was associated with CMV infection (P = 0.004), irregular professional husband's activity was correlated with VZV infection (P = 0.04), and an age of more than 30 years was associated with PB19 infection (P = 0.02). History of rubella, varicella, and PB19 infection was unknown for, respectively, 55.8%, 20%, and 100% of women. False history of rubella and varicella were found for 7.4% and 15% of women, respectively. The positive and negative predictive values (PPV and NPV) of rubella history were, respectively, 92.6% and 17.2%, and were, respectively, 84.9% and 20.9% for varicella history. Susceptibility to RV, VZV, and PB19 infection remains high in pregnancy in our population. Preventive strategies against congenital rubella must be reinforced. Vaccination against VZV should be considered in seronegative women. Systemic CMV screening is not warranted in our country where high immunity is acquired probably in childhood. Since maternal history of eruption is not reliable, we recommend serologic testing to determine immune status of women.

Prevalence of herpes simplex types 1 and 2, varicella zoster virus, cytomegalovirus, immunoglobulin G antibodies among female university students in Syria.

PubMed

Barah, Faraj

2012-09-01

To examine the current seroepidemiology of immunoglobulin (Ig)G for herpes simplex virus types 1 and 2 (HSV 1-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) among university females of childbearing age in Syria. A cross-sectional study was conducted to examine the female students of the Pharmacy College, Kalamoon University, Deratiah, Syria, where 316 sera were collected from October 2009 to November 2010, and subjected to HSV 1-2, VZV, and CMV IgG screening and titration using enzyme-linked immunosorbent assay-based techniques in the Microbiology Laboratory. A total of 164 participants were positive for HSV 1-2 IgG giving a prevalence of 52%, leaving a relatively high proportion of susceptibility among the tested group. For VZV, 91% of the participants (n=287) were positive for its specific IgG, while, regarding CMV, 74.5% (n=235) were positive, and 25.5% were negative for CMV specific IgG. Although most participants were seropositive for herpes viruses IgG, suggesting a natural virus circulation within the community, screening for protective immunity is suggested against HSV, since a relatively high proportion of tested females are still susceptible. In addition, and because of its nasty outcomes during pregnancy, IgG against CMV should also be tested. High percentage of positivity towards VZV could be explained due to introduction of the new vaccine program, and therefore, further analysis during pregnancy is not recommended.

Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus.

PubMed

Reichelt, Mike; Wang, Li; Sommer, Marvin; Perrino, John; Nour, Adel M; Sen, Nandini; Baiker, Armin; Zerboni, Leigh; Arvin, Ann M

2011-02-03

The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant

Comparison of the effects of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate against herpes simplex virus, varicella-zoster virus, and cytomegalovirus with their effects on cellular deoxyribonucleic acid synthesis.

PubMed Central

Gephart, J F; Lerner, A M

1981-01-01

In a single line of human foreskin fibroblasts, minimum inhibitory concentrations (MICs) and the minimum intracellular virus inactivation concentrations (MIICs) of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate were assayed for a number of recent isolates of herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), and cytomegalovirus (CMV). (The term MIIC is used here to describe the selective qualitative intracellular inhibition of the virus inoculum in the primary tissue cultures. The inoculum is not recoverable in subcultures free of antiviral agent.) MICs and MIICs of each of the antiviral agents were readily obtained for each strain of HSV-1, HSV-2, and VZV tested, but all seven strains of CMV tested were much more resistant. At the endpoint, there was little variation in the MICs or MIICs among strans of the same virus. Final MIC results for HSV-1 and HSV-2 were complete after 3 days of incubation; CMV and VZV results required as long as 6 days. The MIC for each herpesvirus increased with incubation, but at the endpoint the MIC and MIIC were approximately equal. VZV was most susceptible to each drug, followed by HSV-1 and HSV-2. The latter two viruses were quite similar. There was no difference in antiviral susceptibilities among any of the strains of HSV-1, HSV-2, VZV, or CMV tested. The toxicities of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate were simultaneously compared by using both microscopic cytotoxicity and inhibition of uptakes of [14C]thymidine into cellular deoxyribonucleic acid and of 14C-labeled amino acids into protein. The selective inhibition of each antiviral agent against viral and cellular deoxyribonucleic acid polymerases was confirmed. Simultaneous assays of antiviral and anticellular activities of antiviral agents may be useful in projecting further in vivo experiments. PMID:6166244

Varicella zoster with erythema multiforme in a young girl: a rare association.

PubMed

Kishore, B Nanda; Ankadavar, Nandini S; Kamath, Ganesh H; Martis, Jacintha

2014-05-01

Erythema multiforme (EM) is an acute, self-limited, mucocutaneous disorder regarded as a hypersensitivity reaction which is triggered by various factors like infection, drugs, and food. Infectious agents are considered to be a major cause of EM other than idiopathic cause. A young girl presented with fluid-filled lesions all over the body of 3 days duration with history of similar lesions with fever in her sibling 2 weeks prior to admission. This was followed by large fluid-filled lesions with halo 3 days thereafter over the trunk, extremities suggesting target lesions of EM. The diagnosis was confirmed by cytology and positive serology. Varicella zoster virus (VZV) has rarely been reported as an etiological agent, despite its high incidence in childhood. VZV as an etiology of EM in a young girl has not been reported so far. This case was reported for its rare association of EM and varicella zoster and also for its rare presentation in a young girl.

Rapid automation of a cell-based assay using a modular approach: case study of a flow-based Varicella Zoster Virus infectivity assay.

PubMed

Joelsson, Daniel; Gates, Irina V; Pacchione, Diana; Wang, Christopher J; Bennett, Philip S; Zhang, Yuhua; McMackin, Jennifer; Frey, Tina; Brodbeck, Kristin C; Baxter, Heather; Barmat, Scott L; Benetti, Luca; Bodmer, Jean-Luc

2010-06-01

Vaccine manufacturing requires constant analytical monitoring to ensure reliable quality and a consistent safety profile of the final product. Concentration and bioactivity of active components of the vaccine are key attributes routinely evaluated throughout the manufacturing cycle and for product release and dosage. In the case of live attenuated virus vaccines, bioactivity is traditionally measured in vitro by infection of susceptible cells with the vaccine followed by quantification of virus replication, cytopathology or expression of viral markers. These assays are typically multi-day procedures that require trained technicians and constant attention. Considering the need for high volumes of testing, automation and streamlining of these assays is highly desirable. In this study, the automation and streamlining of a complex infectivity assay for Varicella Zoster Virus (VZV) containing test articles is presented. The automation procedure was completed using existing liquid handling infrastructure in a modular fashion, limiting custom-designed elements to a minimum to facilitate transposition. In addition, cellular senescence data provided an optimal population doubling range for long term, reliable assay operation at high throughput. The results presented in this study demonstrate a successful automation paradigm resulting in an eightfold increase in throughput while maintaining assay performance characteristics comparable to the original assay. Copyright 2010 Elsevier B.V. All rights reserved.

Update on recommendations for use of herpes zoster vaccine.

PubMed

Hales, Craig M; Harpaz, Rafael; Ortega-Sanchez, Ismael; Bialek, Stephanie R

2014-08-22

Herpes zoster vaccine (Zostavax [Merck & Co., Inc.]) was licensed in 2006 and recommended by the Advisory Committee on Immunization Practices (ACIP) in 2008 for prevention of herpes zoster (shingles) and its complications among adults aged ≥60 years. The Food and Drug Administration (FDA) approved the use of Zostavax in 2011 for adults aged 50 through 59 years based on a large study of safety and efficacy in this age group. ACIP initially considered the use of herpes zoster vaccine among adults aged 50 through 59 years in June 2011, but declined to recommend the vaccine in this age group, citing shortages of Zostavax and limited data on long-term protection afforded by herpes zoster vaccine. In October 2013, ACIP reviewed the epidemiology of herpes zoster and its complications, herpes zoster vaccine supply, short-term vaccine efficacy in adults aged 50 through 59 years, short- and long- term vaccine efficacy and effectiveness in adults aged ≥60 years, an updated cost-effectiveness analysis, and deliberations of the ACIP herpes zoster work group, all of which are summarized in this report. No vote was taken, and ACIP maintained its current recommendation that herpes zoster vaccine be routinely recommended for adults aged ≥60 years. Meeting minutes are available at http://www.cdc.gov/vaccines/acip/meetings/meetings-info.html.

Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.

PubMed

Cunningham, Anthony L; Lal, Himal; Kovac, Martina; Chlibek, Roman; Hwang, Shinn-Jang; Díez-Domingo, Javier; Godeaux, Olivier; Levin, Myron J; McElhaney, Janet E; Puig-Barberà, Joan; Vanden Abeele, Carline; Vesikari, Timo; Watanabe, Daisuke; Zahaf, Toufik; Ahonen, Anitta; Athan, Eugene; Barba-Gomez, Jose F; Campora, Laura; de Looze, Ferdinandus; Downey, H Jackson; Ghesquiere, Wayne; Gorfinkel, Iris; Korhonen, Tiina; Leung, Edward; McNeil, Shelly A; Oostvogels, Lidia; Rombo, Lars; Smetana, Jan; Weckx, Lily; Yeo, Wilfred; Heineman, Thomas C

2016-09-15

A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. In our

Safety, tolerability, and immunogenicity of zoster vaccine in subjects on chronic/maintenance corticosteroids.

PubMed

Russell, Amy F; Parrino, Janie; Fisher, Chester L; Spieler, Wolfgang; Stek, Jon E; Coll, Kathleen E; Su, Shu-Chih; Xu, Jin; Li, Xiaoming; Schlienger, Katia; Silber, Jeffrey L

2015-06-17

This randomized, placebo-controlled study assessed the safety, tolerability, and immunogenicity of live virus zoster vaccine (ZV) in individuals receiving chronic/maintenance systemic corticosteroid therapy (daily dose equivalent of 5-20mg prednisone) for ≥2 weeks prior to vaccination and ≥6 weeks postvaccination. Subjects were followed for adverse experiences (AEs), exposure to varicella or herpes zoster (HZ), or development of varicella/varicella-like or HZ/HZ-like rashes for 42 days postvaccination (primary safety follow-up period) and for serious AEs (SAEs) through Day 182 postvaccination (secondary follow-up period). Varicella-zoster virus (VZV) antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were measured at baseline and at Week 6 postvaccination. The proportions of subjects reporting systemic AEs and SAEs were similar in both groups. A higher percentage of subjects reported injection-site AEs in the ZV group (21.5%) than in the placebo group (12.1%). One SAE of ophthalmic HZ (onset Day 16 postvaccination) was reported in the ZV group and deemed vaccine-related by the study investigator; however, PCR testing confirmed the presence of wild-type (not vaccine strain) VZV. Geometric mean titer (GMT) at 6 weeks postvaccination was higher for ZV recipients than placebo recipients, with estimated geometric mean fold rises (GMFR) of 2.3 (CI: 2.0, 2.7) and 1.1 (CI: 1.0, 1.2) respectfully. In adults ≥60 years old on chronic/maintenance corticosteroids, ZV was generally well tolerated and immunogenic. The VZV-specific gpELISA antibody GMT at 6 weeks postvaccination and the GMFR from baseline to 6 weeks postvaccination were higher in the ZV group than in the placebo group. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sacral herpes-zoster infection presenting as sciatic pain.

PubMed

Ablin, J; Symon, Z; Mevorach, D

1996-06-01

Acute herpes-zoster infection is a painful dermatomal lesion that can be manifested by a wide array of neurologic symptoms. We present a 55-year-old female with non-Hodgkin's lymphoma, who developed a left sciatic pain involving the S roots. Two weeks later, the patient developed fever and vesicular rash over the left gluteal area. Herpes-zoster infection was diagnosed and confirmed by the presence of immunoglobulin M (IgM) antibodies against varicella-zoster. The pain and rash resolved, after treatment with acyclovir. In the appropriate clinical setting, sacral herpes-zoster infection ought to be considered in the differential diagnosis of new-onset sciatic pain.

RNA-seq Analysis of Host and Viral Gene Expression Highlights Interaction between Varicella Zoster Virus and Keratinocyte Differentiation

PubMed Central

Singh, Manuraj; Kanda, Ravinder K.; Yee, Michael B.; Kellam, Paul; Hollinshead, Michael; Kinchington, Paul R.; O'Toole, Edel A.; Breuer, Judith

2014-01-01

Varicella zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterized by epidermal skin blistering. Using a calcium-induced keratinocyte differentiation model we investigated the interaction between epidermal differentiation and VZV infection. RNA-seq analysis showed that VZV infection has a profound effect on differentiating keratinocytes, altering the normal process of epidermal gene expression to generate a signature that resembles patterns of gene expression seen in both heritable and acquired skin-blistering disorders. Further investigation by real-time PCR, protein analysis and electron microscopy revealed that VZV specifically reduced expression of specific suprabasal cytokeratins and desmosomal proteins, leading to disruption of epidermal structure and function. These changes were accompanied by an upregulation of kallikreins and serine proteases. Taken together VZV infection promotes blistering and desquamation of the epidermis, both of which are necessary to the viral spread and pathogenesis. At the same time, analysis of the viral transcriptome provided evidence that VZV gene expression was significantly increased following calcium treatment of keratinocytes. Using reporter viruses and immunohistochemistry we confirmed that VZV gene and protein expression in skin is linked with cellular differentiation. These studies highlight the intimate host-pathogen interaction following VZV infection of skin and provide insight into the mechanisms by which VZV remodels the epidermal environment to promote its own replication and spread. PMID:24497829

Herpes zoster correlates with increased risk of Parkinson's disease in older people

PubMed Central

Lai, Shih-Wei; Lin, Chih-Hsueh; Lin, Hsien-Feng; Lin, Cheng-Li; Lin, Cheng-Chieh; Liao, Kuan-Fu

2017-01-01

Abstract Little is known on the relationship between herpes zoster and Parkinson's disease in older people. This study aimed to explore whether herpes zoster could be associated with Parkinson's disease in older people in Taiwan. We conducted a retrospective cohort study using the claim data of the Taiwan National Health Insurance Program. There were 10,296 subjects aged 65 years and older with newly diagnosed herpes zoster as the herpes zoster group and 39,405 randomly selected subjects aged 65 years and older without a diagnosis of herpes zoster as the nonherpes zoster group from 1998 to 2010. Both groups were followed up until subjects received a diagnosis of Parkinson's disease. This follow-up design would explore whether subjects with herpes zoster were at an increased risk of Parkinson's disease. Relative risks were estimated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the multivariable Cox proportional hazards regression model. The incidence of Parkinson's disease was higher in the herpes zoster group than that in the nonherpes zoster group (4.86 vs 4.00 per 1000 person-years, 95% CI 1.14, 1.29). After adjustment for confounding factors, the multivariable Cox proportional hazards regression model revealed that the adjusted HR of Parkinson's disease was 1.17 for the herpes zoster group (95% CI 1.10, 1.25), compared with the nonherpes zoster group. Older people with herpes zoster confer a slightly increased hazard of developing Parkinson's disease when compared to those without herpes zoster. We think that herpes zoster correlates with increased risk of Parkinson's disease in older people. When older people with herpes zoster seek help, clinicians should pay more attention to the development of the cardinal symptoms of Parkinson's disease. PMID:28207515

Absent anti-N-methyl-D-aspartate receptor NR1a antibodies in herpes simplex virus encephalitis and varicella zoster virus infections.

PubMed

Berger, Benjamin; Pytlik, Maximilian; Hottenrott, Tilman; Stich, Oliver

2017-02-01

A 2012 report and subsequent case series described anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in patients during the acute phase and relapse of herpes simplex virus 1 (HSV1) encephalitis (HSV1E). However, the prevalence of this phenomenon is unknown and systematic studies on other viral infections of the nervous system are missing. We retrospectively analyzed serial cerebrospinal fluid (CSF) and serum samples of consecutive patients treated for neurological HSV1, HSV2 and varicella zoster virus (VZV) infections in our tertiary care university hospital between 2003 and 2013 for the presence of antibodies directed against the NR1a subunit of the NMDAR using indirect immunofluorescence. In total, 88 patients with the following infections were identified through an electronic database search: HSV1 (24 with encephalitis), HSV2 (6 with meningitis, 3 with encephalitis and 1 with myelitis), or VZV (3 with meningitis, 33 with encephalitis, 17 with radiculitis and 1 with myelitis). Two patients with HSV1E and HSV2E, respectively, experienced a clinical relapse. Clinical follow-up was for up to 85 months, and repetitive serum and CSF analyses for up to 43 months. However, at no time did any of the 88 patients exhibit anti-NMDAR NR1a antibodies. In this study, we did not detect anti-NMDAR NR1a antibodies in serial CSF and serum samples of HSV1E patients or patients with other viral infections (HSV2 and VZV). However, the presence of antibodies directed against other epitopes of the NMDAR and other neuronal cell surface antigens cannot be excluded, necessitating further studies.

Urinary retention associated with herpes zoster infection.

PubMed

Cohen, L M; Fowler, J F; Owen, L G; Callen, J P

1993-01-01

Herpes zoster infection particularly involving the sacral dermatomes has been associated with bladder and bowel dysfunction, most commonly urinary retention. We report two patients who developed acute urinary retention, one of whom also had constipation, within days of herpes zoster skin lesions of the S2-S4 dermatomes. Herpes zoster is a reversible cause of neurogenic bladder and bowel dysfunction and should be considered in a patient that presents with acute urinary retention and/or constipation. Sensory abnormalities and flaccid detrusor paralysis are most likely involved in the pathogenesis.

A proteome-scale map of the human interactome network

PubMed Central

Rolland, Thomas; Taşan, Murat; Charloteaux, Benoit; Pevzner, Samuel J.; Zhong, Quan; Sahni, Nidhi; Yi, Song; Lemmens, Irma; Fontanillo, Celia; Mosca, Roberto; Kamburov, Atanas; Ghiassian, Susan D.; Yang, Xinping; Ghamsari, Lila; Balcha, Dawit; Begg, Bridget E.; Braun, Pascal; Brehme, Marc; Broly, Martin P.; Carvunis, Anne-Ruxandra; Convery-Zupan, Dan; Corominas, Roser; Coulombe-Huntington, Jasmin; Dann, Elizabeth; Dreze, Matija; Dricot, Amélie; Fan, Changyu; Franzosa, Eric; Gebreab, Fana; Gutierrez, Bryan J.; Hardy, Madeleine F.; Jin, Mike; Kang, Shuli; Kiros, Ruth; Lin, Guan Ning; Luck, Katja; MacWilliams, Andrew; Menche, Jörg; Murray, Ryan R.; Palagi, Alexandre; Poulin, Matthew M.; Rambout, Xavier; Rasla, John; Reichert, Patrick; Romero, Viviana; Ruyssinck, Elien; Sahalie, Julie M.; Scholz, Annemarie; Shah, Akash A.; Sharma, Amitabh; Shen, Yun; Spirohn, Kerstin; Tam, Stanley; Tejeda, Alexander O.; Trigg, Shelly A.; Twizere, Jean-Claude; Vega, Kerwin; Walsh, Jennifer; Cusick, Michael E.; Xia, Yu; Barabási, Albert-László; Iakoucheva, Lilia M.; Aloy, Patrick; De Las Rivas, Javier; Tavernier, Jan; Calderwood, Michael A.; Hill, David E.; Hao, Tong; Roth, Frederick P.; Vidal, Marc

2014-01-01

SUMMARY Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ~14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ~30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a “broader” human interactome network than currently appreciated. The map also uncovers significant inter-connectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high quality interactome models will help “connect the dots” of the genomic revolution. PMID:25416956

Frequency of Herpes Zoster Recurrence in Central District of Korea.

PubMed

Ha, Jae Won; Lee, Jin Yong; Her, Young; Kim, Chul Woo; Kim, Sang Seok

2017-10-01

Herpes zoster is characterized by unilateral grouped vesicles along the distribution of a dermatome. A global recurrence rate as low as 0.5%∼6.2% has been reported for herpes zoster. The recurrence of herpes zoster is higher in immunocompromised patients and older patients. The purpose of this study is to assess the frequency of herpes zoster recurrence and factors that can influence its recurrence. From January 2005 to December 2015, 14,343 patients with herpes zoster were enrolled in this study. The patients were diagnosed at Hallym University Medical Centers and Kangwon National University Hospital in Seoul, Gyeonggi, and Gangwon. Herpes zoster recurrence and patient characteristics were surveyed by medical record review and a telephonic survey. The overall frequency of herpes zoster recurrence was 1.18%. The frequency of recurrence was higher in women than in men. It was also higher in patients aged 50∼70 years than in patients who were younger or older than this. Additionally, we assessed that the frequency of recurrence was statistically higher in patients with a compromised immune system and in patients who experienced longer lasting pain during their first episode. The frequency of herpes zoster recurrence is more common in women, older age, patient with longer pain duration and immunocompromised patients.

Providers' lack of knowledge about herpes zoster in HIV-infected patients is among barriers to herpes zoster vaccination.

PubMed

Aziz, M; Kessler, H; Huhn, G

2013-06-01

Identification of perceptions about herpes zoster (HZ) disease, vaccine effectiveness and safety, and vaccine recommendations may impact immunization practices of physicians for HIV-infected patients. A survey was used to quantify knowledge of HZ as well as determine physician immunization perceptions and practices. There were 272/1700 respondents (16%). Correct answers for the incidence of varicella zoster virus (VZV) infection in adults and incidence of HZ in HIV-infected patients were recorded by 14% and 10% of providers, respectively. Providers reported poor knowledge of the incidence of disease recurrence in HIV-infected patients (41% correct), potency of HZ vaccine (47.5% correct) and mechanism of protection against reactivation of VZV (66% correct). Most (88%) agreed that HZ was a serious disease, and 73% believed that the burden of disease made vaccination important. A majority (75%) did not vaccinate HIV patients with HZ vaccine regardless of antiretroviral therapy status. Barriers to administration included safety concerns, concern that vaccine would not prevent HZ, risk of HZ dissemination, reimbursement issues and lack of Infectious Diseases Society of America (IDSA) guidelines. Only 38% of providers agreed that CDC guidelines were clear and 50% believed that clinical trials were needed prior to use of HZ vaccine in HIV-infected patients. Education about HZ is needed among HIV providers. Providers perceived vaccination as important, but data on vaccine safety and clear guidance from the CDC on this issue are lacking.

Subclinical Reactivation and Shed of Infectious Varicella Zoster Virus in Saliva of Astronauts

NASA Technical Reports Server (NTRS)

Cohrs, Randall J.; Mehta, Satish K.; Schmid, D. Scott; Gilden, Donald H.; Pierson, Duane L.

2007-01-01

We have previously detected VZV in healthy astronauts both during spaceflight and shortly after landing. Herein, we show that VZV shed in seropositive astronauts is infectious. A total of 40 saliva samples were obtained from each of the 3 astronauts. From each astronaut, 14 samples were taken 109 to 133 days before liftoff, 1 sample was taken every day during 12 days in space, and one sample was taken for 14 consecutive days beginning the second day after landing. Quantitative PCR was used to detect VZV DNA in saliva. None of 42 preflight saliva samples contained VZV DNA. VZV DNA was detected in saliva from 2 of 3 astronauts. In 1 astronaut, 6 of 12 samples obtained during space flight contained 120 to 2,500 copies of VZV DNA per ml; after landing, 1250 copies of VZV DNA were present on day 2, 45 copies on day 3, and 110 copies on day 5. All samples taken 6 to 15 days after touchdown were negative for VZV DNA. In the second astronaut, 5 of 12 samples obtained during space flight contained 18 to 650 copies of VZV DNA per ml; after landing, 560 copies of VZV DNA were present in saliva on day 2, 340 copies on day 4, 45 copies on day 5, and 23 copes on day 6. All samples taken 7 to 15 days after touchdown were negative for VZV DNA. Saliva taken 2 to 6 days after landing from all 3 astronauts was cultured on human fetal lung cells. After one subcultivation, a cytopathic effect developed in cultures inoculated with saliva from the two astronauts whose saliva contained VZV DNA. Both PCR and immunostaining identified the isolates to be VZV and not HSV-1. Importantly, the astronaut in whom no VZV was detected had a history of zoster 9 years earlier. It is possible that a boost in cell-mediated immunity to VZV which is known to develop after zoster protected him from subclinical reactivation. The genotype of the two VZV isolates was determined by VZV ORF22-based PCR/sequencing along with FRET-based PCR assays that target specific nucleotide polymorphisms. Both VZV isolates

Emerging role of the Jun N-terminal kinase interactome in human health.

PubMed

Guo, Xiao-Xi; An, Su; Yang, Yang; Liu, Ying; Hao, Qian; Tang, Tao; Xu, Tian-Rui

2018-02-08

The c-Jun N-terminal kinases (JNKs) are located downstream of Ras-mitogen activated protein kinase signaling cascades. More than 20 years of study has shown that JNKs control cell fate and many cellular functions. JNKs and their interacting proteins form a complicated network with diverse biological functions and physiological effects. Members of the JNK interactome include Jun, amyloid precursor protein, and insulin receptor substrate. Recent studies have shown that the JNK interactome is involved in tumorigenesis, neuron development, and insulin resistance. In this review, we summarize the features of the JNK interactome and classify its members into three groups: upstream regulators, downstream effectors, and scaffold partners. We also highlight the unique cellular signaling mechanisms of JNKs and provide more insights into the roles of the JNK interactome in human diseases. © 2018 International Federation for Cell Biology.

Ocean plankton. Determinants of community structure in the global plankton interactome.

PubMed

Lima-Mendez, Gipsi; Faust, Karoline; Henry, Nicolas; Decelle, Johan; Colin, Sébastien; Carcillo, Fabrizio; Chaffron, Samuel; Ignacio-Espinosa, J Cesar; Roux, Simon; Vincent, Flora; Bittner, Lucie; Darzi, Youssef; Wang, Jun; Audic, Stéphane; Berline, Léo; Bontempi, Gianluca; Cabello, Ana M; Coppola, Laurent; Cornejo-Castillo, Francisco M; d'Ovidio, Francesco; De Meester, Luc; Ferrera, Isabel; Garet-Delmas, Marie-José; Guidi, Lionel; Lara, Elena; Pesant, Stéphane; Royo-Llonch, Marta; Salazar, Guillem; Sánchez, Pablo; Sebastian, Marta; Souffreau, Caroline; Dimier, Céline; Picheral, Marc; Searson, Sarah; Kandels-Lewis, Stefanie; Gorsky, Gabriel; Not, Fabrice; Ogata, Hiroyuki; Speich, Sabrina; Stemmann, Lars; Weissenbach, Jean; Wincker, Patrick; Acinas, Silvia G; Sunagawa, Shinichi; Bork, Peer; Sullivan, Matthew B; Karsenti, Eric; Bowler, Chris; de Vargas, Colomban; Raes, Jeroen

2015-05-22

Species interaction networks are shaped by abiotic and biotic factors. Here, as part of the Tara Oceans project, we studied the photic zone interactome using environmental factors and organismal abundance profiles and found that environmental factors are incomplete predictors of community structure. We found associations across plankton functional types and phylogenetic groups to be nonrandomly distributed on the network and driven by both local and global patterns. We identified interactions among grazers, primary producers, viruses, and (mainly parasitic) symbionts and validated network-generated hypotheses using microscopy to confirm symbiotic relationships. We have thus provided a resource to support further research on ocean food webs and integrating biological components into ocean models. Copyright © 2015, American Association for the Advancement of Science.

Validity of medical record documented varicella-zoster virus among unvaccinated cohorts

PubMed Central

Mohanty, Salini; Perella, Dana; Jumaan, Aisha; Robinson, Donovan; Forke, Christine M; Schmid, D Scott; Renwick, Mia; Mankodi, Foram; Watson, Barbara; Fiks, Alexander G

2013-01-01

Background: A varicella diagnosis or verification of disease history by any healthcare provider is currently accepted for determining evidence of immunity by the Advisory Committee on Immunization Practices (ACIP). Objective: To examine the accuracy of medical record (MR) documented varicella history as a measure of varicella-zoster virus (VZV) immunity among unvaccinated individuals born after 1980. We also assessed methods to practically implement ACIP guidelines to verify varicella history using medical records. Study Design: As part of a larger cross-sectional study conducted at three Philadelphia clinics from 2004–2006, we recruited 536 unvaccinated patients aged 5–19 y (birth years: 1985–2001). Varicella history was obtained from three sources: parent/patient interview, any MR documentation (sick and well visits) and MR documentation of a sick visit for varicella. All participants were tested for VZV IgG. For each source and three age groups (5–9, 10–14, 15–19 y old), positive predictive value (PPV) was calculated. Specificity of varicella history was compared between different sources using McNemar’s Chi-square. Results: Among participants aged 5–9, 10–14 and 15–19 y the PPV for any MR documentation and sick visit diagnosis were 96% and 100%, 92% and 97%, and 99% and 100%, respectively. The specificity for sick visit documentation was higher than any MR documentation and patient/parent recall among all age groups; however, these differences were only statistically significant when comparing sick visit documentation to parent/patient recall for 10-14 y olds. Conclusion: Sick visit documentation of varicella in the MR is an accurate predictor of varicella seropositivity and useful for confirming disease history among unvaccinated persons (birth years: 1985–2001). This method is a practical way to verify varicella history using the ACIP guidelines. PMID:23807363

Herpes Zoster and Dementia: A Nationwide Population-Based Cohort Study.

PubMed

Chen, Vincent Chin-Hung; Wu, Shu-I; Huang, Kuo-You; Yang, Yao-Hsu; Kuo, Ting-Yu; Liang, Hsin-Yi; Huang, Kuan-Lun; Gossop, Michael

Some infectious diseases have been found to be associated with cognitive impairment and dementia. However, the relationship between herpes zoster and dementia has received little attention. This study aimed to investigate this association as well as associations of antiviral treatments for herpes zoster and incident dementia using a large national sample. Cases were identified from the Taiwan National Health Insurance Research Database with a new diagnosis of herpes zoster (ICD-9-CM code: 053) between 1997 and 2013. Each identified individual with a case of herpes zoster was compared with 1 sex-, age-, and residence-matched control subject. Both groups were followed until the first diagnosis of dementia (ICD-9-CM codes: 290.0 to 290.4, 294.1, 331.0 to 331.2, and 331.82), withdrawal from the registry, or the end of 2013. Cox regression analyses and competing risk model were applied, adjusting for sex, age, residence, depression, autoimmune disease, ischemic stroke, traumatic brain injury, alcohol use disorder, and antiviral treatments for herpes zoster to evaluate the risk of interest. A total of 39,205 cases with herpes zoster were identified. Of the 78,410 study and comparison subjects, 4,204 were diagnosed as having dementia during a mean (SD) follow-up period of 6.22 (4.05) years. Herpes zoster was associated with a slightly increased risk of dementia in the fully adjusted model (hazard ratio [HR] = 1.11; 95% CI, 1.04-1.17). Prescriptions of antiviral therapy were associated with a reduced risk of developing dementia following the diagnosis of herpes zoster (HR = 0.55; 95% CI, 0.40-0.77). Herpes zoster was associated with an increased risk of dementia, independent of potential confounding factors. Antiviral treatment might be protective in preventing dementia in patients with herpes zoster. © Copyright 2017 Physicians Postgraduate Press, Inc.

AIM: A comprehensive Arabidopsis Interactome Module database and related interologs in plants

USDA-ARS?s Scientific Manuscript database

Systems biology analysis of protein modules is important for understanding the functional relationships between proteins in the interactome. Here, we present a comprehensive database named AIM for Arabidopsis (Arabidopsis thaliana) interactome modules. The database contains almost 250,000 modules th...

A convex optimization approach for identification of human tissue-specific interactomes.

PubMed

Mohammadi, Shahin; Grama, Ananth

2016-06-15

Analysis of organism-specific interactomes has yielded novel insights into cellular function and coordination, understanding of pathology, and identification of markers and drug targets. Genes, however, can exhibit varying levels of cell type specificity in their expression, and their coordinated expression manifests in tissue-specific function and pathology. Tissue-specific/tissue-selective interaction mechanisms have significant applications in drug discovery, as they are more likely to reveal drug targets. Furthermore, tissue-specific transcription factors (tsTFs) are significantly implicated in human disease, including cancers. Finally, disease genes and protein complexes have the tendency to be differentially expressed in tissues in which defects cause pathology. These observations motivate the construction of refined tissue-specific interactomes from organism-specific interactomes. We present a novel technique for constructing human tissue-specific interactomes. Using a variety of validation tests (Edge Set Enrichment Analysis, Gene Ontology Enrichment, Disease-Gene Subnetwork Compactness), we show that our proposed approach significantly outperforms state-of-the-art techniques. Finally, using case studies of Alzheimer's and Parkinson's diseases, we show that tissue-specific interactomes derived from our study can be used to construct pathways implicated in pathology and demonstrate the use of these pathways in identifying novel targets. http://www.cs.purdue.edu/homes/mohammas/projects/ActPro.html mohammadi@purdue.edu. © The Author 2016. Published by Oxford University Press.

Frequency of Herpes Zoster Recurrence in Central District of Korea

PubMed Central

Ha, Jae Won; Lee, Jin Yong; Her, Young; Kim, Chul Woo

2017-01-01

Background Herpes zoster is characterized by unilateral grouped vesicles along the distribution of a dermatome. A global recurrence rate as low as 0.5%∼6.2% has been reported for herpes zoster. The recurrence of herpes zoster is higher in immunocompromised patients and older patients. Objective The purpose of this study is to assess the frequency of herpes zoster recurrence and factors that can influence its recurrence. Methods From January 2005 to December 2015, 14,343 patients with herpes zoster were enrolled in this study. The patients were diagnosed at Hallym University Medical Centers and Kangwon National University Hospital in Seoul, Gyeonggi, and Gangwon. Herpes zoster recurrence and patient characteristics were surveyed by medical record review and a telephonic survey. Results The overall frequency of herpes zoster recurrence was 1.18%. The frequency of recurrence was higher in women than in men. It was also higher in patients aged 50∼70 years than in patients who were younger or older than this. Additionally, we assessed that the frequency of recurrence was statistically higher in patients with a compromised immune system and in patients who experienced longer lasting pain during their first episode. Conclusion The frequency of herpes zoster recurrence is more common in women, older age, patient with longer pain duration and immunocompromised patients. PMID:28966517

Herpes Zoster and Recurrent Herpes Zoster

PubMed Central

Toyama, Nozomu; Daikoku, Tohru; Yajima, Misako

2017-01-01

Abstract Background. The incidence of recurrent herpes zoster (HZ) and the relationship between initial and recurrent HZ are not clear. Methods. The Miyazaki Dermatologist Society has surveyed ~5000 patients with HZ annually since 1997. A questionnaire regarding HZ and its recurrence was completed by the dermatologists. Results. A total of 34 877 patients with HZ were registered at 43 clinics between June 2009 and November 2015. Among 16 784 patients seen at 10 of the 43 clinics, 1076 patients (6.41%) experienced recurrence. Herpes zoster was more frequent in female than in male patients (5.27 vs 4.25 in 1000 person-years, P < .001), as was HZ recurrence (7.63% vs 4.73%, P < .001). Two and three recurrences were observed in 49 and 3 patients, respectively. Recurrence in the same dermatome was observed in 16.3% of patients, and more frequently this occurred in the left side (P = .027). The number of HZ-experienced persons increased with age, and one third of the population had experienced HZ by the age of 80. Conclusions. Recurrent HZ was observed in 6.41% of patients, with a higher incidence in women. Moreover, HZ experience reduced the HZ incidence to 31.7% of the incidence in the HZ-naive population. PMID:28480280

Zoster-associated segmental paresis in a patient with cervical spinal stenosis.

PubMed

Kang, Sung-Hee; Song, Ho-Kyung; Jang, Yeon

2013-06-01

Segmental zoster paresis is a rare complication of herpes zoster, characterized by focal motor weakness that does not always present simultaneously with skin lesions. Zoster paresis can be easily confused with other neuromuscular or spinal diseases. This case report describes the case of a 72-year-old woman with herpes zoster and cervical spinal stenosis at the same spinal level, where it was difficult to distinguish segmental zoster paresis from cervical radiculopathy combined with motor neuropathy. Although segmental zoster paresis in the upper extremity is rare, it should be included in the differential diagnosis of segmental pain and weakness in the extremities, especially in older or immunocompromised patients. Correct diagnosis is required, to avoid unnecessary surgery and allow timely antiviral treatment.

Domain-based prediction of the human isoform interactome provides insights into the functional impact of alternative splicing.

PubMed

Ghadie, Mohamed Ali; Lambourne, Luke; Vidal, Marc; Xia, Yu

2017-08-01

Alternative splicing is known to remodel protein-protein interaction networks ("interactomes"), yet large-scale determination of isoform-specific interactions remains challenging. We present a domain-based method to predict the isoform interactome from the reference interactome. First, we construct the domain-resolved reference interactome by mapping known domain-domain interactions onto experimentally-determined interactions between reference proteins. Then, we construct the isoform interactome by predicting that an isoform loses an interaction if it loses the domain mediating the interaction. Our prediction framework is of high-quality when assessed by experimental data. The predicted human isoform interactome reveals extensive network remodeling by alternative splicing. Protein pairs interacting with different isoforms of the same gene tend to be more divergent in biological function, tissue expression, and disease phenotype than protein pairs interacting with the same isoforms. Our prediction method complements experimental efforts, and demonstrates that integrating structural domain information with interactomes provides insights into the functional impact of alternative splicing.

Vaccine profile of herpes zoster (HZ/su) subunit vaccine.

PubMed

Cunningham, Anthony L; Heineman, Thomas

2017-07-01

Herpes zoster (HZ) causes an often severe and painful rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN) and by dissemination in immune-compromised patients. HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often associated with age-related or other causes of decreased T cell immunity. A live attenuated vaccine boosts this immunity and provides partial protection against HZ, but this decreases with age and declines over 8 years. Areas covered: A new HZ subunit (HZ/su) vaccine combines a key surface VZV glycoprotein (E) with a T cell-boosting adjuvant system (AS01 B ) and is administered by two intramuscular injections two months apart. Expert commentary: HZ/su showed excellent efficacy of ~90% in immunocompetent adults ≥50 and ≥70 years of age, respectively, in the ZOE-50 and ZOE-70 phase III controlled trials. Efficacy was unaffected by advancing age and persisted for >3 years. Approximately 9.5% of subjects had severe, but transient (1-2 days) injection site pain, swelling or redness. Compliance with both vaccine doses was high (95%). The vaccine will have a major impact on HZ management. Phase I-II trials showed safety and immunogenicity in severely immunocompromised patients. Phase III trial results are expected soon.

Interactome Analysis of NS1 Protein Encoded by Influenza A H7N9 Virus Reveals an Inhibitory Role of NS1 in Host mRNA Maturation.

PubMed

Kuo, Rei-Lin; Chen, Chi-Jene; Tam, Ee-Hong; Huang, Chung-Guei; Li, Li-Hsin; Li, Zong-Hua; Su, Pei-Chia; Liu, Hao-Ping; Wu, Chih-Ching

2018-04-06

Influenza A virus infections can result in severe respiratory diseases. The H7N9 subtype of avian influenza A virus has been transmitted to humans and caused severe disease and death. Nonstructural protein 1 (NS1) of influenza A virus is a virulence determinant during viral infection. To elucidate the functions of the NS1 encoded by influenza A H7N9 virus (H7N9 NS1), interaction partners of H7N9 NS1 in human cells were identified with immunoprecipitation followed by SDS-PAGE coupled with liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). We identified 36 cellular proteins as the interacting partners of the H7N9 NS1, and they are involved in RNA processing, mRNA splicing via spliceosome, and the mRNA surveillance pathway. Two of the interacting partners, cleavage and polyadenylation specificity factor subunit 2 (CPSF2) and CPSF7, were confirmed to interact with H7N9 NS1 using coimmunoprecipitation and immunoblotting based on the previous finding that the two proteins are involved in pre-mRNA polyadenylation machinery. Furthermore, we illustrate that overexpression of H7N9 NS1, as well as infection by the influenza A H7N9 virus, interfered with pre-mRNA polyadenylation in host cells. This study comprehensively profiled the interactome of H7N9 NS1 in host cells, and the results demonstrate a novel endotype for H7N9 NS1 in inhibiting host mRNA maturation.

Vaccination against Herpes Zoster and Postherpetic Neuralgia

PubMed Central

Oxman, Michael N.; Levin, Myron J.

2008-01-01

Background. Herpes zoster (HZ) and postherpetic neuralgia (PHN) cause significant morbidity in older adults. The incidence and severity of HZ and PHN increase with age in association with an age-related decline in varicella-zoster virus (VZV)-specific cell-mediated immunity (VZV-CMI). VZV vaccines can boost VZV-CMI. Therefore, we tested the hypothesis that VZV vaccination would protect older adults against HZ and PHN. Methods. We enrolled 38,546 adults ⩾60 years of age in a randomized, double-blind, placebo-controlled trial of an investigational HZ vaccine and actively followed subjects for the development of HZ. The primary end point was the burden of illness due to HZ (HZ BOI), a composite measure of the incidence, severity, and duration of pain and discomfort caused by HZ. The secondary end point was the incidence of PHN. Results. Subject retention was >95%. HZ vaccine reduced the HZ BOI by 61.1% (95% confidence interval [CI], 51.1%–69.1%; P < .001) and reduced the incidence of PHN by 66.5% (95% CI, 47.5%–79.2%; P < .001). The incidence of HZ was also reduced by 51.3% (95% CI, 44.2%–57.6%; P < .001). HZ vaccine was well tolerated; injection site reactions were generally mild. HZ vaccine neither caused nor induced HZ. Conclusion. The Shingles Prevention Study demonstrated that HZ vaccine significantly reduced the morbidity due to HZ and PHN in older adults. PMID:18419402

Cost-effectiveness of vaccination against herpes zoster.

PubMed

de Boer, Pieter T; Wilschut, Jan C; Postma, Maarten J

2014-01-01

Herpes zoster (HZ) is a common disease among elderly, which may develop into a severe pain syndrome labeled postherpetic neuralgia (PHN). A live-attenuated varicella zoster virus vaccine has been shown to be effective in reducing the incidence and burden of illness of HZ and PHN, providing the opportunity to prevent significant health-related and financial consequences of HZ. In this review, we summarize the available literature on cost-effectiveness of HZ vaccination and discuss critical parameters for cost-effectiveness results. A search in PubMed and EMBASE was performed to identify full cost-effectiveness studies published before April 2013. Fourteen cost-effectiveness studies were included, all performed in western countries. All studies evaluated cost-effectiveness among elderly above 50 years and used costs per quality-adjusted life year (QALY) gained as primary outcome. The vast majority of studies showed vaccination of 60- to 75-year-old individuals to be cost-effective, when duration of vaccine efficacy was longer than 10 years. Duration of vaccine efficacy, vaccine price, HZ incidence, HZ incidence and discount rates were influential to the incremental cost-effectiveness ratio (ICER). HZ vaccination may be a worthwhile intervention from a cost-effectiveness point of view. More extensive reporting on methodology and more detailed results of sensitivity analyses would be desirable to address uncertainty and to guarantee optimal comparability between studies, for example regarding model structure, discounting, vaccine characteristics and loss of quality of life due to HZ and PHN.

Cost-effectiveness of vaccination against herpes zoster

PubMed Central

de Boer, Pieter T; Wilschut, Jan C; Postma, Maarten J

2014-01-01

Herpes zoster (HZ) is a common disease among elderly, which may develop into a severe pain syndrome labeled postherpetic neuralgia (PHN). A live-attenuated varicella zoster virus vaccine has been shown to be effective in reducing the incidence and burden of illness of HZ and PHN, providing the opportunity to prevent significant health-related and financial consequences of HZ. In this review, we summarize the available literature on cost-effectiveness of HZ vaccination and discuss critical parameters for cost-effectiveness results. A search in PubMed and EMBASE was performed to identify full cost-effectiveness studies published before April 2013. Fourteen cost-effectiveness studies were included, all performed in western countries. All studies evaluated cost-effectiveness among elderly above 50 years and used costs per quality-adjusted life year (QALY) gained as primary outcome. The vast majority of studies showed vaccination of 60- to 75-year-old individuals to be cost-effective, when duration of vaccine efficacy was longer than 10 years. Duration of vaccine efficacy, vaccine price, HZ incidence, HZ incidence and discount rates were influential to the incremental cost-effectiveness ratio (ICER). HZ vaccination may be a worthwhile intervention from a cost-effectiveness point of view. More extensive reporting on methodology and more detailed results of sensitivity analyses would be desirable to address uncertainty and to guarantee optimal comparability between studies, for example regarding model structure, discounting, vaccine characteristics and loss of quality of life due to HZ and PHN. PMID:25424815

RNA-Binding Proteins Revisited - The Emerging Arabidopsis mRNA Interactome.

PubMed

Köster, Tino; Marondedze, Claudius; Meyer, Katja; Staiger, Dorothee

2017-06-01

RNA-protein interaction is an important checkpoint to tune gene expression at the RNA level. Global identification of proteins binding in vivo to mRNA has been possible through interactome capture - where proteins are fixed to target RNAs by UV crosslinking and purified through affinity capture of polyadenylated RNA. In Arabidopsis over 500 RNA-binding proteins (RBPs) enriched in UV-crosslinked samples have been identified. As in mammals and yeast, the mRNA interactomes came with a few surprises. For example, a plethora of the proteins caught on RNA had not previously been linked to RNA-mediated processes, for example proteins of intermediary metabolism. Thus, the studies provide unprecedented insights into the composition of the mRNA interactome, highlighting the complexity of RNA-mediated processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Varicella-zoster virus DNA encapsidation genes: Identification and characterization of the putative terminase subunits

PubMed Central

Visalli, Robert J.; Nicolosi, Denise M.; Irven, Karen L.; Goshorn, Bradley; Khan, Tamseel; Visalli, Melissa A.

2007-01-01

The putative DNA encapsidation genes encoded by open reading frames (ORFs) 25, 26, 30, 34, 43, 45/42 and 54 were cloned from Varicella-zoster virus (VZV) strain Ellen. Sequencing revealed that the Ellen ORFs were highly conserved at the amino acid level when compared to those of nineteen previously published VZV isolates. Additionally, RT-PCR provided the first evidence that ORF45/42 was expressed as a spliced transcript in VZV-infected cells. All seven ORFs were expressed in vitro and full length products were identified using a C-terminal V5 epitope tag. The in vitro products of the putative VZV terminase subunits encoded by ORFs 30 and 45/42 proved useful in protein-protein interaction assays. Previous studies have reported the formation of a heterodimeric terminase complex involved in DNA encapsidation for both herpes simplex virus-type 1 (HSV-1) and human cytomegalovirus (HCMV). Here we report that the C-terminal portion of exon II of ORF45/42 (ORF42-C269) interacted in GST-pull down experiments with in vitro synthesized ORF30 and ORF45/42. The interactions were maintained in the presence of anionic detergents and in buffers of increasing ionic strength. Cells transiently transfected with epitope tagged ORF45/42 or ORF30 showed primarily cytoplasmic staining. In contrast, an antiserum directed to the N-terminal portion of ORF45 showed nearly exclusive nuclear localization of the ORF45/42 gene product in infected cells. An ORF30 specific antiserum detected an 87 kDa protein in both the cytoplasmic and nuclear fractions of VZV infected cells. The results were consistent with the localization and function of herpesviral terminase subunits. This is the first study aimed at the identification and characterization of the VZV DNA encapsidation gene products. PMID:17868947

The Glycoprotein B Cytoplasmic Domain Lysine Cluster Is Critical for Varicella-Zoster Virus Cell-Cell Fusion Regulation and Infection

PubMed Central

Arvin, Ann M.; Oliver, Stefan L.

2016-01-01

ABSTRACT The conserved glycoproteins gB and gH-gL are essential for herpesvirus entry and cell-cell fusion induced syncytium formation, a characteristic of varicella-zoster virus (VZV) pathology in skin and sensory ganglia. VZV syncytium formation, which has been implicated in the painful condition of postherpetic neuralgia, is regulated by the cytoplasmic domains of gB (gBcyt) via an immunoreceptor tyrosine-based inhibition motif (ITIM) and gH (gHcyt). A lysine cluster (K894, K897, K898, and K900) in the VZV gBcyt was identified by sequence alignment to be conserved among alphaherpesviruses, suggesting a functional role. Alanine and arginine substitutions were used to determine if the positive charge and susceptibility to posttranslational modifications of these lysines contributed to gB/gH-gL cell-cell fusion. Critically, the positive charge of the lysine residues was necessary for fusion regulation, as alanine substitutions induced a 440% increase in fusion compared to that of the wild-type gBcyt while arginine substitutions had wild-type-like fusion levels in an in vitro gB/gH-gL cell fusion assay. Consistent with these results, the alanine substitutions in the viral genome caused exaggerated syncytium formation, reduced VZV titers (−1.5 log10), and smaller plaques than with the parental Oka (pOka) strain. In contrast, arginine substitutions resulted in syncytia with only 2-fold more nuclei, a −0.5-log10 reduction in titers, and pOka-like plaques. VZV mutants with both an ITIM mutation and either alanine or arginine substitutions had reduced titers and small plaques but differed in syncytium morphology. Thus, effective VZV propagation is dependent on cell-cell fusion regulation by the conserved gBcyt lysine cluster, in addition to the gBcyt ITIM and the gHcyt. IMPORTANCE Varicella-zoster virus (VZV) is a ubiquitous pathogen that causes chickenpox and shingles. Individuals afflicted with shingles risk developing the painful condition of postherpetic

Effectiveness of herpes zoster vaccination in an older United Kingdom population.

PubMed

Walker, Jemma L; Andrews, Nick J; Amirthalingam, Gayatri; Forbes, Harriet; Langan, Sinead M; Thomas, Sara L

2018-04-19

Vaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71-79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed. In a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013-31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN. Among 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year. This first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining

A protein domain-based interactome network for C. elegans early embryogenesis

PubMed Central

Boxem, Mike; Maliga, Zoltan; Klitgord, Niels; Li, Na; Lemmens, Irma; Mana, Miyeko; de Lichtervelde, Lorenzo; Mul, Joram D.; van de Peut, Diederik; Devos, Maxime; Simonis, Nicolas; Yildirim, Muhammed A.; Cokol, Murat; Kao, Huey-Ling; de Smet, Anne-Sophie; Wang, Haidong; Schlaitz, Anne-Lore; Hao, Tong; Milstein, Stuart; Fan, Changyu; Tipsword, Mike; Drew, Kevin; Galli, Matilde; Rhrissorrakrai, Kahn; Drechsel, David; Koller, Daphne; Roth, Frederick P.; Iakoucheva, Lilia M.; Dunker, A. Keith; Bonneau, Richard; Gunsalus, Kristin C.; Hill, David E.; Piano, Fabio; Tavernier, Jan; van den Heuvel, Sander; Hyman, Anthony A.; Vidal, Marc

2008-01-01

Summary Many protein-protein interactions are mediated through independently folding modular domains. Proteome-wide efforts to model protein-protein interaction or “interactome” networks have largely ignored this modular organization of proteins. We developed an experimental strategy to efficiently identify interaction domains and generated a domain-based interactome network for proteins involved in C. elegans early embryonic cell divisions. Minimal interacting regions were identified for over 200 proteins, providing important information on their domain organization. Furthermore, our approach increased the sensitivity of the two-hybrid system, resulting in a more complete interactome network. This interactome modeling strategy revealed new insights into C. elegans centrosome function and is applicable to other biological processes in this and other organisms. PMID:18692475

Centrality in the host-pathogen interactome is associated with pathogen fitness during infection.

PubMed

Crua Asensio, Núria; Muñoz Giner, Elisabet; de Groot, Natalia Sánchez; Torrent Burgas, Marc

2017-01-16

To perform their functions proteins must interact with each other, but how these interactions influence bacterial infection remains elusive. Here we demonstrate that connectivity in the host-pathogen interactome is directly related to pathogen fitness during infection. Using Y. pestis as a model organism, we show that the centrality-lethality rule holds for pathogen fitness during infection but only when the host-pathogen interactome is considered. Our results suggest that the importance of pathogen proteins during infection is directly related to their number of interactions with the host. We also show that pathogen proteins causing an extensive rewiring of the host interactome have a higher impact in pathogen fitness during infection. Hence, we conclude that hubs in the host-pathogen interactome should be explored as promising targets for antimicrobial drug design.

Centrality in the host-pathogen interactome is associated with pathogen fitness during infection

NASA Astrophysics Data System (ADS)

Crua Asensio, Núria; Muñoz Giner, Elisabet; de Groot, Natalia Sánchez; Torrent Burgas, Marc

2017-01-01

To perform their functions proteins must interact with each other, but how these interactions influence bacterial infection remains elusive. Here we demonstrate that connectivity in the host-pathogen interactome is directly related to pathogen fitness during infection. Using Y. pestis as a model organism, we show that the centrality-lethality rule holds for pathogen fitness during infection but only when the host-pathogen interactome is considered. Our results suggest that the importance of pathogen proteins during infection is directly related to their number of interactions with the host. We also show that pathogen proteins causing an extensive rewiring of the host interactome have a higher impact in pathogen fitness during infection. Hence, we conclude that hubs in the host-pathogen interactome should be explored as promising targets for antimicrobial drug design.

Varicella Seroprevalence and Molecular Epidemiology of Varicella-Zoster Virus in Argentina, 2002

PubMed Central

Dayan, Gustavo H.; Panero, María S.; Debbag, Roberto; Urquiza, Ana; Molina, Marta; Prieto, Susana; del Carmen Perego, María; Scagliotti, Graciela; Galimberti, Diana; Carroli, Guillermo; Wolff, Cristina; Schmid, D. Scott; Loparev, Vladimir; Guris, Dalya; Seward, Jane

2004-01-01

There is limited data on immunity against varicella-zoster virus (VZV) in adults in different parts of Argentina, and it is not known which VZV strains are circulating in Argentina. The objectives of this study were as follows: (i) to evaluate seroprevalence of varicella among adults, assessing the accuracy of clinical history and determining the sociodemographic factors associated with seropositivity; and (ii) to determine the VZV strains circulating in Argentina. A cross-sectional serological survey enrolling 2,807 women aged 15 to 49 years attending public health-care settings in four cities in Argentina (i.e., Buenos Aires, Salta, Mendoza, and Rosario) and one rural area was conducted from August to November 2002. Specimens for identification of VZV strains were obtained from vesicular lesions from 13 pediatric patients with varicella from different areas of the country. PCR amplification was used for genotyping. The overall seroprevalence of varicella antibodies was 98.5% (95% confidence interval, 98.0 to 98.9), ranging from 97.2% in central Buenos Aires to 99.3% in southern Buenos Aires and Salta. Varicella seroprevalence increased with age. Crowding and length of residence in the same place were associated with seropositivity. The positive predictive value of varicella history for immunity to varicella was 99.4%; however, the negative predictive value was 2.5%. The European genotype was identified in all viral specimens. In Argentina, seroprevalence in women more than 15 years old was high regardless of the area of residence. Negative or uncertain varicella history was not a good predictor of immunity. VZV genotype was stable in all areas of the country. PMID:15583301

Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years.

PubMed

Schmader, Kenneth E; Levin, Myron J; Gnann, John W; McNeil, Shelly A; Vesikari, Timo; Betts, Robert F; Keay, Susan; Stek, Jon E; Bundick, Nickoya D; Su, Shu-Chih; Zhao, Yanli; Li, Xiaoming; Chan, Ivan S F; Annunziato, Paula W; Parrino, Janie

2012-04-01

Herpes zoster (HZ) adversely affects individuals aged 50-59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50-59 years. This was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50-59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for ≥1 year (mean, 1.3 years) postvaccination until accrual of ≥96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination. The ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1-80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups. In subjects aged 50-59 years, the ZV significantly reduced the incidence of HZ and was well tolerated. NCT00534248.

[Recurrent herpes zoster with neuralgia].

PubMed

Schwickert, Myriam; Saha, Joyonto

2006-06-01

We present the case of a 40-year-old female patient suffering from recurrent herpes zoster and postherpetic neuralgia. Herpes zoster has recurred several times per year for more than 15 years. At admission, rash localised on the right sacral region and accompanied by neuralgia had lasted for 3 months. Standard out-patient treatment remained unsuccessful. A multimodal integrative therapy regimen including fasting, hydrotherapy, leech application and treatment with autologous blood led to rapid healing of herpetic lesions and persistent pain relief. The case is discussed.

Disease burden and epidemiology of herpes zoster in pre-vaccine Taiwan.

PubMed

Lin, Yung-Hsiu; Huang, Li-Min; Chang, I-Shou; Tsai, Fang-Yu; Lu, Chun-Yi; Shao, Pei-Lan; Chang, Luan-Yin

2010-02-03

Herpes zoster, a common disease, has an important impact on the health of adults, particularly the elderly, and the health system. This study evaluated the disease burden and epidemiological characteristics of herpes zoster in Taiwan. Using herpes zoster-related ICD-9-CM codes used on Taiwan's National Health Insurance claims, we analyzed overall and age group differences in incidence, complications, utilization of healthcare facilities, lengths of stay, and cost of their medical care in Taiwan's population from 2000 to 2005. The overall annual incidence of zoster was 4.97 cases per 1000 people, with women having a significantly higher incidence than men (5.20 per 1000 vs. 4.72 per 1000, p<0.001). The incidence increased stepwise with age, with 5.18 cases per 1000 in people 40-50 years old, 8.36 in those 50-60, 11.09 in those 60-70, and 11.77 in those above 70 years old. The estimated lifetime risk of developing herpes zoster was 32.2%. Zoster-related hospitalizations and medical cost per patient increased with age. In conclusion, about two-thirds of Taiwan's zoster cases occur in adults older than 40 years old and about one-third of the population would develop zoster within their lifetime. (c) 2009 Elsevier Ltd. All rights reserved.

The Effects of School Holidays on Transmission of Varicella Zoster Virus, England and Wales, 1967–2008

PubMed Central

Jackson, Charlotte; Mangtani, Punam; Fine, Paul; Vynnycky, Emilia

2014-01-01

Background Changes in children’s contact patterns between termtime and school holidays affect the transmission of several respiratory-spread infections. Transmission of varicella zoster virus (VZV), the causative agent of chickenpox, has also been linked to the school calendar in several settings, but temporal changes in the proportion of young children attending childcare centres may have influenced this relationship. Methods We used two modelling methods (a simple difference equations model and a Time series Susceptible Infectious Recovered (TSIR) model) to estimate fortnightly values of a contact parameter (the per capita rate of effective contact between two specific individuals), using GP consultation data for chickenpox in England and Wales from 1967–2008. Results The estimated contact parameters were 22–31% lower during the summer holiday than during termtime. The relationship between the contact parameter and the school calendar did not change markedly over the years analysed. Conclusions In England and Wales, reductions in contact between children during the school summer holiday lead to a reduction in the transmission of VZV. These estimates are relevant for predicting how closing schools and nurseries may affect an outbreak of an emerging respiratory-spread pathogen. PMID:24932994

Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies.

PubMed

Parrino, Janie; McNeil, Shelly A; Lawrence, Steven J; Kimby, Eva; Pagnoni, Marco F; Stek, Jon E; Zhao, Yanli; Chan, Ivan S F; Kaplan, Susan S

2017-03-27

Immunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZV IN ) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZV IN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80). This was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZV IN regimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZV IN would elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4. ZV IN elicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-value<0.001), meeting the pre-specified success criterion. Overall, 85% (68/80) of patients reported ⩾1 AE, 44% (35/80) reported ⩾1 injection-site AE, and 74% (59/80) reported ⩾1 systemic AE. The majority of systemic AEs were non-serious and considered unrelated to vaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZV IN had rash polymerase chain reaction (PCR) positive for VZV vaccine strain. In adults with HM receiving anti

Prevention of Herpes Zoster and its complications: From clinical evidence to real life experience.

PubMed

Gabutti, Giovanni; Bonanni, Paolo; Conversano, Michele; Fanelli, Guido; Franco, Elisabetta; Greco, Donato; Icardi, Giancarlo; Lazzari, Marzia; Rossi, Alessandro; Scotti, Silvestro; Volpi, Antonio

2017-02-01

Herpes zoster (HZ) is an acute viral illness characterized by a vesicular rash with unilateral distribution, which can also result in severe complications such as post-herpetic neuralgia (PHN), ophthalmic zoster, stroke or other neurological complications. The estimate incidence in Europe ranges between 2.0 and 4.6 cases per 1,000 person-years, with a sharp increase in >50 year-old subjects. Currently, treatment options for HZ are only partially effective in limiting the acute phase, while the management of complications is complex and often unsatisfactory. The total burden of the disease and the high costs related to its diagnostic and therapeutic management led researchers to develop a new preventive approach through a live attenuated virus vaccine. The currently available vaccine, with a high antigen content, is safe, well tolerated and reduces the incidence of HZ, PHN and the burden of illness. Several countries have introduced this vaccination, albeit with different recommendations and methods of financing. Taking into account the barriers to this immunization registered in some areas (difficulty of vaccine distribution, lack of physician recommendations, the cost of vaccine for patients, etc.), this group of Italian experts advocate that a common strategy able to guarantee a good compliance with this vaccination should be implemented. The same group addresses some practical questions concerning the use of zoster vaccine.

Prevention of Herpes Zoster and its complications: From clinical evidence to real life experience

PubMed Central

Gabutti, Giovanni; Bonanni, Paolo; Conversano, Michele; Fanelli, Guido; Greco, Donato; Lazzari, Marzia; Rossi, Alessandro; Scotti, Silvestro; Volpi, Antonio

2017-01-01

ABSTRACT Herpes zoster (HZ) is an acute viral illness characterized by a vesicular rash with unilateral distribution, which can also result in severe complications such as post-herpetic neuralgia (PHN), ophthalmic zoster, stroke or other neurological complications. The estimate incidence in Europe ranges between 2.0 and 4.6 cases per 1,000 person-years, with a sharp increase in >50 year-old subjects. Currently, treatment options for HZ are only partially effective in limiting the acute phase, while the management of complications is complex and often unsatisfactory. The total burden of the disease and the high costs related to its diagnostic and therapeutic management led researchers to develop a new preventive approach through a live attenuated virus vaccine. The currently available vaccine, with a high antigen content, is safe, well tolerated and reduces the incidence of HZ, PHN and the burden of illness. Several countries have introduced this vaccination, albeit with different recommendations and methods of financing. Taking into account the barriers to this immunization registered in some areas (difficulty of vaccine distribution, lack of physician recommendations, the cost of vaccine for patients, etc.), this group of Italian experts advocate that a common strategy able to guarantee a good compliance with this vaccination should be implemented. The same group addresses some practical questions concerning the use of zoster vaccine. PMID:27925894

Mapping the Small Molecule Interactome by Mass Spectrometry.

PubMed

Flaxman, Hope A; Woo, Christina M

2018-01-16

Mapping small molecule interactions throughout the proteome provides the critical structural basis for functional analysis of their impact on biochemistry. However, translation of mass spectrometry-based proteomics methods to directly profile the interaction between a small molecule and the whole proteome is challenging because of the substoichiometric nature of many interactions, the diversity of covalent and noncovalent interactions involved, and the subsequent computational complexity associated with their spectral assignment. Recent advances in chemical proteomics have begun fill this gap to provide a structural basis for the breadth of small molecule-protein interactions in the whole proteome. Innovations enabling direct characterization of the small molecule interactome include faster, more sensitive instrumentation coupled to chemical conjugation, enrichment, and labeling methods that facilitate detection and assignment. These methods have started to measure molecular interaction hotspots due to inherent differences in local amino acid reactivity and binding affinity throughout the proteome. Measurement of the small molecule interactome is producing structural insights and methods for probing and engineering protein biochemistry. Direct structural characterization of the small molecule interactome is a rapidly emerging area pushing new frontiers in biochemistry at the interface of small molecules and the proteome.

Pangaea and the Out-of-Africa Model of Varicella-Zoster Virus Evolution and Phylogeography.

PubMed

Grose, Charles

2012-09-01

The goal of this minireview is to provide an overview of varicella-zoster virus (VZV) phylogenetics and phylogeography when placed in the broad context of geologic time. Planet Earth was formed over 4 billion years ago, and the supercontinent Pangaea coalesced around 400 million years ago (mya). Based on detailed tree-building models, the base of the phylogenetic tree of the Herpesviridae family has been estimated at 400 mya. Subsequently, Pangaea split into Laurasia and Gondwanaland; in turn, Africa rifted from Gondwanaland. Based on available data, the hypothesis of this minireview is that the ancestral alphaherpesvirus VZV coevolved in simians, apes, and hominins in Africa. When anatomically modern humans first crossed over the Red Sea 60,000 years ago, VZV was carried along in their dorsal root ganglia. Currently, there are five VZV clades, distinguishable by single nucleotide polymorphisms. These clades likely represent continued VZV coevolution, as humans with latent VZV infection left Arabia and dispersed into Asia (clades 2 and 5) and Europe (clades 1, 3, and 4). The prototype VZV sequence contains nearly 125,000 bp, divided into 70 open reading frames. Generally, isolates within a clade display >99.9% identity to one another, while members of one clade compared to a second clade show 99.8% identity to one another. Recently, four different VZV genotypes that do not segregate into the previously defined five clades have been identified, a result indicating a wider than anticipated diversity among newly collected VZV strains around the world.

Molecular analysis of varicella vaccines and varicella-zoster virus from vaccine-related skin lesions.

PubMed

Thiele, Sonja; Borschewski, Aljona; Küchler, Judit; Bieberbach, Marc; Voigt, Sebastian; Ehlers, Bernhard

2011-07-01

To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF) orf62 sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV.

Next-Generation Technologies for Multiomics Approaches Including Interactome Sequencing

PubMed Central

Ohashi, Hiroyuki; Miyamoto-Sato, Etsuko

2015-01-01

The development of high-speed analytical techniques such as next-generation sequencing and microarrays allows high-throughput analysis of biological information at a low cost. These techniques contribute to medical and bioscience advancements and provide new avenues for scientific research. Here, we outline a variety of new innovative techniques and discuss their use in omics research (e.g., genomics, transcriptomics, metabolomics, proteomics, and interactomics). We also discuss the possible applications of these methods, including an interactome sequencing technology that we developed, in future medical and life science research. PMID:25649523

Disease networks. Uncovering disease-disease relationships through the incomplete interactome.

PubMed

Menche, Jörg; Sharma, Amitabh; Kitsak, Maksim; Ghiassian, Susan Dina; Vidal, Marc; Loscalzo, Joseph; Barabási, Albert-László

2015-02-20

According to the disease module hypothesis, the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data have sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant coexpression patterns, symptom similarity, and comorbidity, whereas diseases residing in separated network neighborhoods are phenotypically distinct. These tools represent an interactome-based platform to predict molecular commonalities between phenotypically related diseases, even if they do not share primary disease genes. Copyright © 2015, American Association for the Advancement of Science.

Domain-based prediction of the human isoform interactome provides insights into the functional impact of alternative splicing

PubMed Central

Lambourne, Luke; Vidal, Marc

2017-01-01

Alternative splicing is known to remodel protein-protein interaction networks (“interactomes”), yet large-scale determination of isoform-specific interactions remains challenging. We present a domain-based method to predict the isoform interactome from the reference interactome. First, we construct the domain-resolved reference interactome by mapping known domain-domain interactions onto experimentally-determined interactions between reference proteins. Then, we construct the isoform interactome by predicting that an isoform loses an interaction if it loses the domain mediating the interaction. Our prediction framework is of high-quality when assessed by experimental data. The predicted human isoform interactome reveals extensive network remodeling by alternative splicing. Protein pairs interacting with different isoforms of the same gene tend to be more divergent in biological function, tissue expression, and disease phenotype than protein pairs interacting with the same isoforms. Our prediction method complements experimental efforts, and demonstrates that integrating structural domain information with interactomes provides insights into the functional impact of alternative splicing. PMID:28846689

[Herpes zoster infection with acute urinary retention].

PubMed

Jakab, G; Komoly, S; Juhász, E

1990-03-11

The history of a young female patient is presented. She developed urine retention of sudden onset as a complication of herpes zoster infection manifested in the sacral dermatomes. Symptomatic and antiviral treatments were introduced with full recovery of bladder function. The correct diagnosis of this rare and benign complication of herpes zoster infection can help to avoid unnecessary and invasive examinations.

The Hepatitis E virus intraviral interactome.

PubMed

Osterman, Andreas; Stellberger, Thorsten; Gebhardt, Anna; Kurz, Marisa; Friedel, Caroline C; Uetz, Peter; Nitschko, Hans; Baiker, Armin; Vizoso-Pinto, Maria G

2015-10-14

Hepatitis E virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (Kd) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs.

Infected Peripheral Blood Mononuclear Cells Transmit Latent Varicella Zoster Virus Infection to the Guinea Pig Enteric Nervous System

PubMed Central

Gan, Lin; Wang, Mingli; Chen, Jason J.; Gershon, Michael D.; Gershon, Anne A.

2014-01-01

Latent wild-type (WT) and vaccine (vOka) varicella-zoster virus (VZV) are found in the human enteric nervous system (ENS). VZV also infects guinea pig enteric neurons in vitro, establishes latency and can be reactivated. We therefore determined whether lymphocytes infected in vitro with VZV secrete infectious virions and can transfer infection in vivo to the ENS of recipient guinea pigs. T lymphocytes (CD3-immunoreactive) were preferentially infected following co-culture of guinea pig or human peripheral blood mononuclear cells with VZV-infected HELF. VZV proliferated in the infected T cells and expressed immediate early and late VZV genes. Electron microscopy confirmed that VZV-infected T cells produced encapsulated virions. Extracellular virus, however, was pleomorphic, suggesting degradation occurred prior to release, which was confirmed by the failure of VZV-infected T cells to secrete infectious virions. Intravenous injection of WT- or vOka-infected PBMCs, nevertheless, transmitted VZV to recipient animals (guinea pig > human lymphocytes). Two days post-inoculation, lung and liver, but not gut, contained DNA and transcripts encoding ORFs 4, 40, 66 and 67. Twenty-eight days after infection, gut contained DNA and transcripts encoding ORFs 4 and 66 but neither DNA nor transcripts could any longer be found in lung or liver. In situ hybridization revealed VZV DNA in enteric neurons, which also expressed ORF63p (but not ORF68p) immunoreactivity. Observations suggest that VZV infects T cells, which can transfer VZV to and establish latency in enteric neurons in vivo. Guinea pigs may be useful for studies of VZV pathogenesis in the ENS. PMID:24965252

Review of the Persistence of Herpes Zoster Vaccine Efficacy in Clinical Trials.

PubMed

Cook, Stephen J; Flaherty, Dennis K

2015-11-01

The live attenuated herpes zoster vaccine(*) was approved for the prevention of shingles in 2006. Initial Phase III clinical trials proved vaccine efficacy persisted during the study duration; however, assessment of long-term efficacy required additional studies. This article reviews efficacy data for the zoster vaccine that have been published since 2004. It focuses on studies assessing declining vaccine efficacy. MEDLINE, EMBASE, CENTRAL, and CINAHL databases were searched for zoster vaccine efficacy trials. Randomized controlled trials published from 2004 to 2015 were included in the review. Six studies were included in the review. The zoster vaccine reduced the risk of herpes zoster by 51.3% to 72.4% in 2 Phase III trials. Primary and other analyses showed the vaccine was effective at reducing the burden of illness (61.1%), postherpetic neuralgia (66.5%), disease interference on functional status (66.2%), and disease impact on health-related quality of life (55%) compared with placebo. Surveillance studies showed a decrease in vaccine efficacy for reducing the incidence of herpes zoster during follow-up years 3.3 to 7.8 (39.6% relative reduction) and 4.7 to 11.6 (21.1% relative reduction). Initial zoster vaccine efficacy is significant, but declines in post-vaccination years 3 to 11. This raises the question about the need for possible revaccination with the zoster vaccine. Clinicians should consider the declining efficacy when administering the zoster vaccine to patients. Future studies will need to address the impact of the varicella vaccine on the incidence of shingles and whether this impacts the efficacy of the zoster vaccine. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Neurogenic bladder from occult herpes zoster.

PubMed

Rothrock, J F; Walicke, P A; Swenson, M R

1986-11-01

Active infection with herpes zoster may cause acute urinary retention, especially when it involves sacral dermatomes. Although frank retention usually develops days to weeks after eruption of the typical rash, bladder incompetence infrequently develops first, raising concern over other, more ominous etiologies. In the case presented, rash appearance was delayed until six weeks after the initial onset of urinary retention, a much longer interval than previously reported. Occult herpes zoster infection should be considered in patients presenting with an acute neurogenic bladder of obscure cause.

Simultaneous Cocirculation of Both European Varicella-Zoster Virus Genotypes (E1 and E2) in Mexico City▿

PubMed Central

Rodríguez-Castillo, Araceli; Vaughan, Gilberto; Ramírez-González, José Ernesto; Escobar-Gutiérrez, Alejandro

2010-01-01

Full-length genome analysis of varicella-zoster virus (VZV) has shown that viral strains can be classified into seven different genotypes: European (E), Mosaic (M), and Japanese (J), and the E and M genotypes can be further subclassified into E1, E2, and M1 through 4, respectively. The distribution of the main VZV genotypes in Mexico was described earlier, demonstrating the predominance of E genotype, although other genotypes (M1 and M4) were also identified. However, no information regarding the circulation of either E genotype in the country is available. In the present study, we confirm the presence of both E1 and E2 genotypes in the country and explore the possibility of coinfection as the triggering factor for increased virulence among severe cases. A total of 61 different European VZV isolates collected in the Mexico City metropolitan area from 2005 to 2006 were typed by using a PCR method based on genotype-specific primer amplification. Fifty isolates belonged to the E1 genotype, and the eleven remaining samples were classified as E2 genotypes. No coinfection with both E genotypes was identified among these specimens. We provide here new information on the distribution of VZV genotypes circulating in Mexico City. PMID:20220168

Pangaea and the Out-of-Africa Model of Varicella-Zoster Virus Evolution and Phylogeography

PubMed Central

2012-01-01

The goal of this minireview is to provide an overview of varicella-zoster virus (VZV) phylogenetics and phylogeography when placed in the broad context of geologic time. Planet Earth was formed over 4 billion years ago, and the supercontinent Pangaea coalesced around 400 million years ago (mya). Based on detailed tree-building models, the base of the phylogenetic tree of the Herpesviridae family has been estimated at 400 mya. Subsequently, Pangaea split into Laurasia and Gondwanaland; in turn, Africa rifted from Gondwanaland. Based on available data, the hypothesis of this minireview is that the ancestral alphaherpesvirus VZV coevolved in simians, apes, and hominins in Africa. When anatomically modern humans first crossed over the Red Sea 60,000 years ago, VZV was carried along in their dorsal root ganglia. Currently, there are five VZV clades, distinguishable by single nucleotide polymorphisms. These clades likely represent continued VZV coevolution, as humans with latent VZV infection left Arabia and dispersed into Asia (clades 2 and 5) and Europe (clades 1, 3, and 4). The prototype VZV sequence contains nearly 125,000 bp, divided into 70 open reading frames. Generally, isolates within a clade display >99.9% identity to one another, while members of one clade compared to a second clade show 99.8% identity to one another. Recently, four different VZV genotypes that do not segregate into the previously defined five clades have been identified, a result indicating a wider than anticipated diversity among newly collected VZV strains around the world. PMID:22761371

Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis

PubMed Central

McDonald, Jay R.; Zeringue, Angelique L.; Caplan, Liron; Ranganathan, Prabha; Xian, Hong; Burroughs, Thomas E.; Fraser, Victoria J; Cunningham, Fran; Eisen, Seth A.

2009-01-01

Background Herpes zoster occurs more commonly in patients taking immunosuppressive medications, though the risk associated with different medications is poorly understood. Methods Retrospective cohort study including 20,357 patients who were followed in the Veterans Affairs healthcare system and treated for rheumatoid arthritis from October 1998 through June 2005. Cox proportional hazards regression was used to determine risk factors for herpes zoster, and herpes zoster-free survival. Chart review was performed to validate the diagnosis of herpes zoster. Results The incidence of herpes zoster was 9.96 per 1000 patient-years. In time-to-event analysis, patients receiving medications used to treat mild rheumatoid arthritis were less likely to have an episode of herpes zoster than patients receiving medications used to treat moderate and severe rheumatoid arthritis (p<0.001). Independent risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, malignancy, chronic lung disease, renal failure, and liver disease. Among patients receiving tumor necrosis factor-alpha antagonists, etanercept (HR 0.62) and adalimumab (HR 0.53) were associated with lower risk of herpes zoster. There was excellent agreement between ICD-9-CM diagnosis of herpes zoster and diagnosis by chart review (kappa = 0.92). Conclusions Risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, and several comorbid medical conditions. These results demonstrate that the Department of Veterans Affairs’ national administrative databases can be used to study rare adverse drug events. PMID:19368499

Detection of Vero Cells Infected with Herpes Simplex Types 1 and 2 and Varicella Zoster Viruses Using Raman Spectroscopy and Advanced Statistical Methods.

PubMed

Huleihel, Mahmoud; Shufan, Elad; Zeiri, Leila; Salman, Ahmad

2016-01-01

Of the eight members of the herpes family of viruses, HSV1, HSV2, and varicella zoster are the most common and are mainly involved in cutaneous disorders. These viruses usually are not life-threatening, but in some cases they might cause serious infections to the eyes and the brain that can lead to blindness and possibly death. An effective drug (acyclovir and its derivatives) is available against these viruses. Therefore, early detection and identification of these viral infections is highly important for an effective treatment. Raman spectroscopy, which has been widely used in the past years in medicine and biology, was used as a powerful spectroscopic tool for the detection and identification of these viral infections in cell culture, due to its sensitivity, rapidity and reliability. Our results showed that it was possible to differentiate, with a 97% identification success rate, the uninfected Vero cells that served as a control, from the Vero cells that were infected with HSV-1, HSV-2, and VZV. For that, linear discriminant analysis (LDA) was performed on the Raman spectra after principal component analysis (PCA) with a leave one out (LOO) approach. Raman spectroscopy in tandem with PCA and LDA enable to differentiate among the different herpes viral infections of Vero cells in time span of few minutes with high accuracy rate. Understanding cell molecular changes due to herpes viral infections using Raman spectroscopy may help in early detection and effective treatment.

The cost-effectiveness of varicella and combined varicella and herpes zoster vaccination programmes in the United Kingdom.

PubMed

van Hoek, Albert Jan; Melegaro, Alessia; Gay, Nigel; Bilcke, Joke; Edmunds, W John

2012-02-01

Despite the existence of varicella vaccine, many developed countries have not introduced it into their national schedules, partly because of concerns about whether herpes zoster (HZ, shingles) will increase due to a lack of exogenous boosting. The magnitude of any increase in zoster that might occur is dependent on rates at which adults and children mix - something that has only recently been quantified - and could be reduced by simultaneously vaccinating older individuals against shingles. This study is the first to assess the cost-effectiveness of combined varicella and zoster vaccination options and compare this to alternative programmes. The cost-effectiveness of various options for the use of varicella-zoster virus (VZV) containing vaccines was explored using a transmission dynamic model. Underlying contact rates are estimated from a contemporary survey of social mixing patterns, and uncertainty in these derived from bootstrapping the original sample. The model was calibrated to UK data on varicella and zoster incidence. Other parameters were taken from the literature. UK guidance on perspective and discount rates were followed. The results of the incremental cost-effectiveness analysis suggest that a combined policy is cost-effective. However, the cost-effectiveness of this policy (and indeed the childhood two-dose policy) is influenced by projected benefits that accrue many decades (80-100 years or more) after the start of vaccination. If the programme is evaluated over shorter time frames, then it would be unlikely to be deemed cost-effective, and may result in declines in population health, due to a projected rise in the incidence of HZ. The findings are also sensitive to a number of parameters that are inaccurately quantified, such as the risk of HZ in varicella vaccine responders. Policy makers should be aware of the potential negative benefits in the first 30-50 years after introduction of a childhood varicella vaccine. This can only be partly mitigated

A case of anti aquapolin-4 antibody positive myelitis with hyperhidrosis, following herpes zoster.

PubMed

Suda, Machiko; Tsutsumiuchi, Michiko; Uesaka, Yoshikazu; Hayashi, Nobukazu

2017-01-31

We report an acute myelitis in a 53-year-old woman that occurred in 7 days after the diagnosis of Th5-6 herpes zoster. Clinical examination revealed hyperhidrosis of left side of her face, neck, arm and upper chest. She also had muscle weakness of her left leg and sensory impairment for light touch and temperature in her chest and legs. Spinal cord MRI demonstrated a longitudinal T 2 -hyperintense lesion extending from Th1 to 7. In the axial imaging, the lesion dominantly located in the left side gray matter. Hyperhidrosis, weakness and sensory impairment were improved after intravenous therapy with acyclovir and methylprednisolone. VZV (varicella zoster virus) IgG index of the cerebrospinal fluid was high and serological anti aquaporin-4 antibodies were positive at the time of the admission. This case had both characteristics of VZV myelitis and neuromyelitis optica spectrum disorder. Myelitis relapsed 19 months after the first attack. We believe that sympathetic hyper reactivity due to thoracic spinal cord lesion was responsible for the hyperhidrosis in our patient.

Unusually severe varicella zoster (VZV) virus viral (aseptic) meningitis in an unimmunized, immunocompetent host with chickenpox.

PubMed

Cunha, Burke A; Warren-Favorito, Heather; Mickail, Nardeen

2011-01-01

Chickenpox is caused by the varicella zoster virus (VZV) and may be more severe in adults than in children. Central nervous system (CNS) manifestations of chickenpox and VZV are uncommon, for example, encephalitis and cerebellar ataxis. Viral (aseptic) meningitis is a rare CNS complication of VZV. The cerebrospinal fluid (CSF) profile in VZV viral (aseptic) meningitis is indistinguishable from other causes of viral meningitis. The clue to most of the diagnoses of VZV aseptic meningitis is based on the temporal relationship between antecedent or concomitant chickenpox. Chickenpox is a clinical diagnosis based on the appearance and distribution of the rash. The rash of chickenpox is vesicular/pruritic and typically appears in crops over 3 successive days. VZV vesicles are fragile, superficial, and surrounded by a erythematous halo. Common nonspecific laboratory findings in chickenpox include leukopenia, thrombocytopenia, and elevated serum transaminases (serum glutamate-oxaloacetate transaminase/serum glutamate-pyruvate transaminase). The erythrocyte sedimentation rate (ESR) is not highly elevated in chickenpox. In VZV aseptic meningitis, the CSF shows a lymphocytic pleocytosis with normal protein, glucose, and lactic acid levels. CSF red blood cells are not a feature of VZV meningitis. We present the case of a healthy unimmunized adult who was hospitalized with chickenpox complicated by VZV aseptic meningitis with an unusually severe headache and nuchal rigidity that occurred during hospitalization. Copyright © 2011 Elsevier Inc. All rights reserved.

Varicella Zoster Virus Induces Nuclear Translocation of the Neurokinin-1 Receptor, Promoting Lamellipodia Formation and Viral Spread in Spinal Astrocytes.

PubMed

Bubak, Andrew N; Como, Christina N; Blackmon, Anna M; Frietze, Seth; Mescher, Teresa; Jones, Dallas; Cohrs, Randall J; Paucek, Petr; Baird, Nicholas L; Nagel, Maria A

2018-05-19

Varicella zoster virus (VZV) can present as a myelopathy with spinal astrocyte infection. Recent studies support a role for the neurokinin-1 receptor (NK-1R) in virus infections, as well as for cytoskeletal alterations that may promote viral spread. Thus, we examined the role of NK-1R in VZV-infected primary human spinal astrocytes (HA-sps) to shed light on the pathogenesis of VZV myelopathy. Mock- and VZV-infected HA-sps were examined for substance P (subP) production, NK-1R localization, morphological changes and viral spread in the presence or absence of NK-1R antagonists, aprepitant and rolapitant. VZV infection of HA-sps induced nuclear localization of full-length and truncated NK-1R in the absence of the endogenous ligand, subP, and was associated with extensive lamellipodia formation and viral spread that was inhibited by NK-1R antagonists. We have identified a novel, subP-independent, proviral function of nuclear NK-1R associated with lamellipodia formation and viral spread that is distinct from subP-induced NK-1R cell membrane/cytoplasmic localization without lamellipodia formation. These results suggest that binding of a putative viral ligand to NK-1R produces a dramatically different NK-1R downstream effect than binding of subP. Finally, NK-1R antagonists aprepitant and rolapitant provide promising alternatives to nucleoside analogs in treating VZV infections, including myelopathy.

A predicted protein interactome identifies conserved global networks and disease resistance subnetworks in maize

USDA-ARS?s Scientific Manuscript database

An interactome is the genome-wide roadmap of protein-protein interactions that occur within an organism. Interactomes for humans, the fruit fly, and now plants such as Arabidopsis thaliana and Oryza sativa have been generated using high throughput experimental methods. It is possible to use these ...

∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis.

PubMed

Pankow, Sandra; Bamberger, Casimir; Calzolari, Diego; Martínez-Bartolomé, Salvador; Lavallée-Adam, Mathieu; Balch, William E; Yates, John R

2015-12-24

Deletion of phenylalanine 508 of the cystic fibrosis transmembrane conductance regulator (∆F508 CFTR) is the major cause of cystic fibrosis, one of the most common inherited childhood diseases. The mutated CFTR anion channel is not fully glycosylated and shows minimal activity in bronchial epithelial cells of patients with cystic fibrosis. Low temperature or inhibition of histone deacetylases can partly rescue ∆F508 CFTR cellular processing defects and function. A favourable change of ∆F508 CFTR protein-protein interactions was proposed as a mechanism of rescue; however, CFTR interactome dynamics during temperature shift and inhibition of histone deacetylases are unknown. Here we report the first comprehensive analysis of the CFTR and ∆F508 CFTR interactome and its dynamics during temperature shift and inhibition of histone deacetylases. By using a novel deep proteomic analysis method, we identify 638 individual high-confidence CFTR interactors and discover a ∆F508 deletion-specific interactome, which is extensively remodelled upon rescue. Detailed analysis of the interactome remodelling identifies key novel interactors, whose loss promote ∆F508 CFTR channel function in primary cystic fibrosis epithelia or which are critical for CFTR biogenesis. Our results demonstrate that global remodelling of ∆F508 CFTR interactions is crucial for rescue, and provide comprehensive insight into the molecular disease mechanisms of cystic fibrosis caused by deletion of F508.

Loss of urinary voiding sensation due to herpes zoster.

PubMed

Hiraga, Akiyuki; Nagumo, Kiyomi; Sakakibara, Ryuji; Kojima, Shigeyuki; Fujinawa, Naoto; Hashimoto, Tasuku

2003-01-01

A case of sacral herpes zoster infection in a 56-year-old man with the complication of loss of urinary voiding sensation is presented. He had typical herpes zoster eruption on the left S2 dermatome, hypalgesia of the S1-S4 dermatomes, and absence of urinary voiding sensation. There was no other urinary symptom at the first medical examination. Urinary complications associated with herpes zoster are uncommon, but two types, acute cystitis and acute retention, have been recognized. No cases of loss of urinary voiding sensation due to herpes zoster have been reported. In this case, hypalgesia of the sacral dermatomes was mild compared to the marked loss of urethral sensation. This inconsistency is explained by the hypothesis that the number of urethral fibers is very small as compared to that of cutaneous fibers, therefore, urethral sensation would be more severely disturbed than cutaneous sensation. Copyright 2003 Wiley-Liss, Inc.

Community and patient values for preventing herpes zoster.

PubMed

Lieu, Tracy A; Ortega-Sanchez, Ismael; Ray, G Thomas; Rusinak, Donna; Yih, W Katherine; Choo, Peter W; Shui, Irene; Kleinman, Ken; Harpaz, Rafael; Prosser, Lisa A

2008-01-01

The US Advisory Committee on Immunization Practices has recently recommended a new vaccine against herpes zoster (shingles) for routine use in adults aged > or =60 years. However, estimates of the cost effectiveness of this vaccine vary widely, in part because of gaps in the data on the value of preventing herpes zoster. Our aims were to (i) generate comprehensive information on the value of preventing a range of outcomes of herpes zoster; (ii) compare these values among community members and patients with shingles and post-herpetic neuralgia (PHN); and (iii) identify clinical and demographic characteristics that explain the variation in these values. Community members drawn from a nationally representative survey research panel (n = 527) completed an Internet-based survey using time trade-off and willingness-to-pay questions to value a series of scenarios that described cases of herpes zoster with varying pain intensities (on a scale of 0 to 10, where 0 represents no pain and 10 represents the worst imaginable pain) and duration (30 days to 1 year). Patients with shingles (n = 382) or PHN (n = 137) [defined as having symptoms for > or =90 days] from two large healthcare systems completed telephone interviews with similar questions to the Internet-based survey and also answered questions about their current experience with herpes zoster. We constructed generalized linear mixed models to evaluate the associations between demographic and clinical characteristics, the length and intensity of the health states and time trade-off and willingness-to-pay values. In time trade-off questions, community members offered a mean of 89 (95% CI 24, 182) discounted days to avoid the least severe scenario (pain level of 3 for 1 month) and a mean of 162 (95% CI 88, 259) discounted days to avoid the most severe scenario (pain level of 8 for 12 months). Compared with patients with shingles, community members traded more days to avoid low-severity scenarios but similar numbers of days

Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na+/K+ transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses

PubMed Central

Iwasaki, Masaharu; Caì, Yíngyún; de la Torre, Juan C.

2018-01-01

Several mammalian arenaviruses (mammarenaviruses) cause hemorrhagic fevers in humans and pose serious public health concerns in their endemic regions. Additionally, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. Concerns about human-pathogenic mammarenaviruses are exacerbated by of the lack of licensed vaccines, and current anti-mammarenavirus therapy is limited to off-label use of ribavirin that is only partially effective. Detailed understanding of virus/host-cell interactions may facilitate the development of novel anti-mammarenavirus strategies by targeting components of the host-cell machinery that are required for efficient virus multiplication. Here we document the generation of a recombinant LCMV encoding a nucleoprotein (NP) containing an affinity tag (rLCMV/Strep-NP) and its use to capture the NP-interactome in infected cells. Our proteomic approach combined with genetics and pharmacological validation assays identified ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) and prohibitin (PHB) as pro-viral factors. Cell-based assays revealed that ATP1A1 and PHB are involved in different steps of the virus life cycle. Accordingly, we observed a synergistic inhibitory effect on LCMV multiplication with a combination of ATP1A1 and PHB inhibitors. We show that ATP1A1 inhibitors suppress multiplication of Lassa virus and Candid#1, a live-attenuated vaccine strain of Junín virus, suggesting that the requirement of ATP1A1 in virus multiplication is conserved among genetically distantly related mammarenaviruses. Our findings suggest that clinically approved inhibitors of ATP1A1, like digoxin, could be repurposed to treat infections by mammarenaviruses pathogenic for humans. PMID:29462184

Distribution of Health Effects and Cost-effectiveness of Varicella Vaccination are Shaped by the Impact on Herpes Zoster.

PubMed

van Lier, Alies; Lugnér, Anna; Opstelten, Wim; Jochemsen, Petra; Wallinga, Jacco; Schellevis, François; Sanders, Elisabeth; de Melker, Hester; van Boven, Michiel

2015-10-01

Varicella zoster virus (VZV) is the etiological agent of varicella and herpes zoster (HZ). It has been hypothesised that immune boosting of latently infected persons by contact with varicella reduces the probability of HZ. If true, universal varicella vaccination may increase HZ incidence due to reduced VZV circulation. To inform decision-making, we conduct cost-effectiveness analyses of varicella vaccination, including effects on HZ. Effects of varicella vaccination are simulated with a dynamic transmission model, parameterised with Dutch VZV seroprevalence and HZ incidence data, and linked to an economic model. We consider vaccination scenarios that differ by whether or not they include immune boosting, and reactivation of vaccine virus. Varicella incidence decreases after introduction of vaccination, while HZ incidence may increase or decrease depending on whether or not immune boosting is present. Without immune boosting, vaccination is expected to be cost-effective or even cost-saving. With immune boosting, vaccination at 95% coverage is not expected to be cost-effective, and may even cause net health losses. Cost-effectiveness of varicella vaccination depends strongly on the impact on HZ and the economic time horizon. Our findings reveal ethical dilemmas as varicella vaccination may result in unequal distribution of health effects between generations.

Development of a multiplex real-time PCR for the simultaneous detection of herpes simplex and varicella zoster viruses in cerebrospinal fluid and lesion swab specimens.

PubMed

Wong, Anita A; Pabbaraju, Kanti; Wong, Sallene; Tellier, Raymond

2016-03-01

Herpes simplex viruses (HSV) and varicella zoster virus (VZV) can have very similar and wide-ranging clinical presentations. Rapid identification is necessary for timely antiviral therapy, especially with infections involving the central nervous system, neonates, and immunocompromised individuals. Detection of HSV-1, HSV-2 and VZV was combined into one real-time PCR reaction utilizing hydrolysis probes. The assay was validated on the LightCycler(®) (Roche) and Applied Biosystems 7500 Real-Time PCR System (Thermo Fisher Scientific Inc.) to detect alphaherpesviruses in cerebral spinal fluid (CSF) and lesion swab specimens, respectively. Validation data on blood and tissue samples are also presented. The multiplex assay showed excellent sensitivity, specificity and reproducibility when compared to two singleplex real-time PCR assays for CSF samples and direct fluorescent antigen/culture for lesion swab samples. Implementation of the multiplex assay has facilitated improved sensitivity and accuracy as well as reduced turn-around-times and costs. The results from a large data set of 16,622 prospective samples tested between August 16, 2012 to February 1, 2014 at the Provincial Laboratory for Public Health (Alberta, Canada) are presented here. Copyright © 2015 Elsevier B.V. All rights reserved.

Herpes zoster induced neuropathic bladder--a case report.

PubMed

Tsai, Hsiu-Nan; Wu, Wen-Jeng; Huang, Shu-Pin; Su, Chin-Ming; Chen, Chung-Chin; Wang, Chii-Jye; Chou, Yii-Her; Huang, Chun-Hsiung

2002-01-01

Herpes zoster infection involving the sacral dermatomes has been associated with bladder dysfunction and, although rarely, with acute urinary retention. Less than 150 cases have been reported in the literature. After reviewing our institute's chart records covering a period of time dating from 1991 to 2001, we found that three of our patients had developed acute urinary retention following herpes zoster skin lesions of the S2-4 dermatomes. Herein we report our findings. These three patients had previously been found to have normal voiding status. However, at the time of complaint urodynamic studies revealed detrusor areflexia or detrusor hyporeflexia with decreased sensation of bladder filling. After micturation recovery, repeat urodynamic studies revealed detrusor pressure and bladder sensation recovery. After one to six weeks of treatment, all three patients could void spontaneously without catheterization. We found that, when treated with antiviral medication, supportive analgesics, and temporary urinary drainage, which included urethral catheterization and suprapubic cystostomy, acute urinary retention associated with herpes zoster has a generally favorable prognosis. In other words, we found that in spite of its rarity, herpes zoster induced neuropathic bladder dysfunction is reversible when treated appropriately.

mRNA interactome capture in mammalian cells.

PubMed

Kastelic, Nicolai; Landthaler, Markus

2017-08-15

Throughout their entire life cycle, mRNAs are associated with RNA-binding proteins (RBPs), forming ribonucleoprotein (RNP) complexes with highly dynamic compositions. Their interplay is one key to control gene regulatory mechanisms from mRNA synthesis to decay. To assay the global scope of RNA-protein interactions, we and others have published a method combining crosslinking with highly stringent oligo(dT) affinity purification to enrich proteins associated with polyadenylated RNA (poly(A)+ RNA). Identification of the poly(A)+ RNA-bound proteome (also: mRNA interactome capture) has by now been applied to a diversity of cell lines and model organisms, uncovering comprehensive repertoires of RBPs and hundreds of novel RBP candidates. In addition to determining the RBP catalog in a given biological system, mRNA interactome capture allows the examination of changes in protein-mRNA interactions in response to internal and external stimuli, altered cellular programs and disease. Copyright © 2017. Published by Elsevier Inc.

Comprehensive interactome of Otx2 in the adult mouse neural retina.

PubMed

Fant, Bruno; Samuel, Alexander; Audebert, Stéphane; Couzon, Agnès; El Nagar, Salsabiel; Billon, Nathalie; Lamonerie, Thomas

2015-11-01

The Otx2 homeodomain transcription factor exerts multiple functions in specific developmental contexts, probably through the regulation of different sets of genes. Protein partners of Otx2 have been shown to modulate its activity. Therefore, the Otx2 interactome may play a key role in selecting a precise target-gene repertoire, hence determining its function in a specific tissue. To address the nature of Otx2 interactome, we generated a new recombinant Otx2(CTAP-tag) mouse line, designed for protein complexes purification. We validated this mouse line by establishing the Otx2 interactome in the adult neural retina. In this tissue, Otx2 is thought to have overlapping function with its paralog Crx. Our analysis revealed that, in contrary to Crx, Otx2 did not develop interactions with proteins that are known to regulate phototransduction genes but showed specific partnership with factors associated with retinal development. The relationship between Otx2 and Crx in the neural retina should therefore be considered as complementarity rather than redundancy. Furthermore, study of the Otx2 interactome revealed strong associations with RNA processing and translation machineries, suggesting unexpected roles for Otx2 in the regulation of selected target genes all along the transcription/translation pathway. The Otx2(CTAP-tag) line, therefore, appears suitable for a systematic approach to Otx2 protein-protein interactions. genesis 53:685-694, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Vernet syndrome resulting from varicella zoster virus infection-a very rare clinical presentation of a common viral infection.

PubMed

Ferreira, João; Franco, Ana; Teodoro, Tiago; Coelho, Miguel; Albuquerque, Luísa

2018-03-12

Vernet syndrome is a unilateral palsy of glossopharyngeal, vagus, and accessory nerves. Varicella zoster virus (VZV) infection has rarely been described as a possible cause. A 76-year-old man presented with 1-week-long symptoms of dysphonia, dysphagia, and weakness of the right shoulder elevation, accompanied by a mild right temporal parietal headache with radiation to the ipsilateral ear. Physical examination showed signs compatible with a right XI, X, and XI cranial nerves involvement and also several vesicular lesions in the right ear's concha. He had a personal history of poliomyelitis and chickenpox. Laringoscopy demonstrated right vocal cord palsy. Brain MRI showed thickening and enhancement of right lower cranial nerves and an enhancing nodular lesion in the ipsilateral jugular foramen, in T1 weighted images with gadolinium. Cerebrospinal fluid (CSF) analysis disclosed a mild lymphocytic pleocytosis and absence of VZV-DNA by PCR analysis. Serum VZV IgM and IgG antibodies were positive. The patient had a noticeable clinical improvement after initiation of acyclovir and prednisolone therapy. The presentation of a VZV infection with isolated IX, X, and XI cranial nerves palsy is extremely rare. In our case, the diagnosis of Vernet syndrome as a result of VZV infection was made essentially from clinical findings and supported by analytical and imaging data.

Receptor Tyrosine Kinase MET Interactome and Neurodevelopmental Disorder Partners at the Developing Synapse

PubMed Central

Xie, Zhihui; Li, Jing; Baker, Jonathan; Eagleson, Kathie L.; Coba, Marcelo P.; Levitt, Pat

2016-01-01

Background Atypical synapse development and plasticity are implicated in many neurodevelopmental disorders (NDDs). NDD-associated, high confidence risk genes have been identified, yet little is known about functional relationships at the level of protein-protein interactions, which are the dominant molecular bases responsible for mediating circuit development. Methods Proteomics in three independent developing neocortical synaptosomal preparations identified putative interacting proteins of the ligand-activated MET receptor tyrosine kinase, an autism risk gene that mediates synapse development. The candidates were translated into interactome networks and analyzed bioinformatically. Additionally, three independent quantitative proximity ligation assays (PLA) in cultured neurons and four independent immunoprecipitation analyses of synaptosomes validated protein interactions. Results Approximately 11% (8/72) of MET-interacting proteins, including SHANK3, SYNGAP1 and GRIN2B, are associated with NDDs. Proteins in the MET interactome were translated into a novel MET interactome network based on human protein-protein interaction databases. High confidence genes from different NDD datasets that encode synaptosomal proteins were analyzed for being enriched in MET interactome proteins. This was found for autism, but not schizophrenia, bipolar disorder, major depressive disorder or attentional deficit hyperactivity disorder. There is correlated gene expression between MET and its interactive partners in developing human temporal and visual neocortices, but not with highly expressed genes that are not in the interactome. PLA and biochemical analyses demonstrate that MET-protein partner interactions are dynamically regulated by receptor activation. Conclusions The results provide a novel molecular framework for deciphering the functional relations of key regulators of synaptogenesis that contribute to both typical cortical development and to NDDs. PMID:27086544

Herpes zoster in African patients: an early manifestation of HIV infection.

PubMed

Van de Perre, P; Bakkers, E; Batungwanayo, J; Kestelyn, P; Lepage, P; Nzaramba, D; Bogaerts, J; Serufilira, A; Rouvroy, D; Uwimana, A

1988-01-01

During a 3-month period, 131 cases of herpes zoster were diagnosed in Kigali, Rwanda. There were 46 female and 85 male patients. Mean age was 29 years (range 1-66). An unusually high proportion of patients presented with cranial and sacral nerve localisation of their cutaneous lesions. 55/131 patients (42%) had involvement of more than one dermatome. None of the patients had an underlying condition known to favour herpes zoster. 120/131 (92%) had antibodies to HIV detected by an immunoenzymatic assay (EIA) and indirect immunofluorescence. 92/125 adult patients (74%) had no sign or symptom related to HIV infection other than herpes zoster. This study suggests that herpes zoster in Central Africa is an early and readily detectable manifestation of HIV-induced immunosuppression.

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience

PubMed Central

Willis, English D.; Woodward, Meredith; Brown, Elizabeth; Popmihajlov, Zoran; Saddier, Patricia; Annunziato, Paula W.; Halsey, Neal A.; Gershon, Anne A.

2017-01-01

Background Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. Methods All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. Results A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. Conclusions The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies. PMID:29174682

Herpes zoster with dysfunction of bladder and anus.

PubMed

Jellinek, E H; Tulloch, W S

1976-12-04

Herpes zoster may give rise to dysfunction of bladder and anus. Mucosal lesions have been reported, and 7 cases are described with retention, loss of sensation, or incontinence. Sacral shingles is associated with sensory loss and flaccid detrusor paralysis. Lumbar shingles may cause retention, and zoster at higher levels can also damage the spinal cord. Recovery is usually complete. The implication for schemes of bladder innervation is discussed.

Schizophrenia interactome with 504 novel protein–protein interactions

PubMed Central

Ganapathiraju, Madhavi K; Thahir, Mohamed; Handen, Adam; Sarkar, Saumendra N; Sweet, Robert A; Nimgaonkar, Vishwajit L; Loscher, Christine E; Bauer, Eileen M; Chaparala, Srilakshmi

2016-01-01

Genome-wide association studies of schizophrenia (GWAS) have revealed the role of rare and common genetic variants, but the functional effects of the risk variants remain to be understood. Protein interactome-based studies can facilitate the study of molecular mechanisms by which the risk genes relate to schizophrenia (SZ) genesis, but protein–protein interactions (PPIs) are unknown for many of the liability genes. We developed a computational model to discover PPIs, which is found to be highly accurate according to computational evaluations and experimental validations of selected PPIs. We present here, 365 novel PPIs of liability genes identified by the SZ Working Group of the Psychiatric Genomics Consortium (PGC). Seventeen genes that had no previously known interactions have 57 novel interactions by our method. Among the new interactors are 19 drug targets that are targeted by 130 drugs. In addition, we computed 147 novel PPIs of 25 candidate genes investigated in the pre-GWAS era. While there is little overlap between the GWAS genes and the pre-GWAS genes, the interactomes reveal that they largely belong to the same pathways, thus reconciling the apparent disparities between the GWAS and prior gene association studies. The interactome including 504 novel PPIs overall, could motivate other systems biology studies and trials with repurposed drugs. The PPIs are made available on a webserver, called Schizo-Pi at http://severus.dbmi.pitt.edu/schizo-pi with advanced search capabilities. PMID:27336055

Transcriptional mapping of the varicella-zoster virus regulatory genes encoding open reading frames 4 and 63.

PubMed Central

Kinchington, P R; Vergnes, J P; Defechereux, P; Piette, J; Turse, S E

1994-01-01

Four of the 68 varicella-zoster virus (VZV) unique open reading frames (ORFs), i.e., ORFs 4, 61, 62, and 63, encode proteins that influence viral transcription and are considered to be positional homologs of herpes simplex virus type 1 (HSV-1) immediate-early (IE) proteins. In order to identify the elements that regulate transcription of VZV ORFs 4 and 63, the encoded mRNAs were mapped in detail. For ORF 4, a major 1.8-kb and a minor 3.0-kb polyadenylated [poly(A)+] RNA were identified, whereas ORF 63-specific probes recognized 1.3- and 1.9-kb poly(A)+ RNAs. Probes specific for sequences adjacent to the ORFs and mapping of the RNA 3' ends indicated that the ORF 4 RNAs were 3' coterminal, whereas the RNAs for ORF 63 represented two different termination sites. S1 nuclease mapping and primer extension analyses indicated a single transcription initiation site for ORF 4 at 38 bp upstream of the ORF start codon. For ORF 63, multiple transcriptional start sites at 87 to 95, 151 to 153, and (tentatively) 238 to 243 bp upstream of the ORF start codon were identified. TATA box motifs at good positional locations were found upstream of all mapped transcription initiation sites. However, no sequences resembling the TAATGARAT motif, which confers IE regulation upon HSV-1 IE genes, were found. The finding of the absence of this motif was supported through analyses of the regulatory sequences of ORFs 4 and 63 in transient transfection assays alongside those of ORFs 61 and 62. Sequences representing the promoters for ORFs 4, 61, and 63 were all stimulated by VZV infection but failed to be stimulated by coexpression with the HSV-1 transactivator Vmw65. In contrast, the promoter for ORF 62, which contains TAATGARAT motifs, was activated by VZV infection and coexpression with Vmw65. These results extend the transcriptional knowledge for VZV and suggest that ORFs 4 and 63 contain regulatory signals different from those of the ORF 62 and HSV-1 IE genes. Images PMID:8189496

Comprehensive Identification of RNA-Binding Proteins by RNA Interactome Capture.

PubMed

Castello, Alfredo; Horos, Rastislav; Strein, Claudia; Fischer, Bernd; Eichelbaum, Katrin; Steinmetz, Lars M; Krijgsveld, Jeroen; Hentze, Matthias W

2016-01-01

RNA associates with RNA-binding proteins (RBPs) from synthesis to decay, forming dynamic ribonucleoproteins (RNPs). In spite of the preeminent role of RBPs regulating RNA fate, the scope of cellular RBPs has remained largely unknown. We have recently developed a novel and comprehensive method to identify the repertoire of active RBPs of cultured cells, called RNA interactome capture. Using in vivo UV cross-linking on cultured cells, proteins are covalently bound to RNA if the contact between the two is direct ("zero distance"). Protein-RNA complexes are purified by poly(A) tail-dependent oligo(dT) capture and analyzed by quantitative mass spectrometry. Because UV irradiation is applied to living cells and purification is performed using highly stringent washes, RNA interactome capture identifies physiologic and direct protein-RNA interactions. Applied to HeLa cells, this protocol revealed the near-complete repertoire of RBPs, including hundreds of novel RNA binders. Apart from its RBP discovery capacity, quantitative and comparative RNA interactome capture can also be used to study the responses of the RBP repertoire to different physiological cues and processes, including metabolic stress, differentiation, development, or the response to drugs.

Seroepidemiology of varicella-zoster virus infection in a cosmopolitan city (Erzurum) in the eastern Turkey.

PubMed

Alp, Handan; Altinkaynak, Sevin; Ertekin, Vildan; Kiliçaslan, Buket; Giiraksin, Asuman

2005-04-01

The aim of the study was to determine VZV seroprevalence under age 30 and to identify the relationship of VZV seroprevalence and several sociodemographic characteristics of the study subjects. The results were presented in order to design a strategy for vaccination against varicella-zoster virus (VZV). It was planned to include a total of 568 subjects. The sampling method of 30 clusters recommended for field studies was used for selecting subjects of a predetermined number in the rural and urban areas in eastern Turkey. ELISA method was used to examine the blood samples for VZV seropositivity. Age, gender, place of living, educational level, family size and socioeconomic status was investigated in the study subjects. Positive VZV seroprevalence was detected in 78% of 559 subjects. Seroprevalence increased with age. Seroprevalence was 16.67% at the age of 1 year, subsequently increased to 57.58% at the age of 4 years, 70% at the age of 7 years, 92.31% at the age of 10 years and then remained 86.78-96.36% in subjects over the age of 10 years. No association was found between sociodemographic variables studied and prevalence levels of antibodies except for educational level in the 0-14 year group. These results suggest that the majority of VZV infections occur during the early childhood; the best option to reduce the circulation of wild type VZV in the population would be the immunization of young children. VZV vaccine should be introduced into the routine childhood vaccination programme in Turkey.

Post-licensure safety surveillance of zoster vaccine live (Zostavax®) in the United States, Vaccine Adverse Event Reporting System (VAERS), 2006-2015.

PubMed

Miller, Elaine R; Lewis, Paige; Shimabukuro, Tom T; Su, John; Moro, Pedro; Woo, Emily Jane; Jankosky, Christopher; Cano, Maria

2018-03-26

Herpes zoster (HZ), or shingles, is caused by reactivation of varicella-zoster virus in latently infected individuals. Live-attenuated HZ vaccine (zoster vaccine live, ZVL) is approved in the United States for persons aged ≥50 years and recommended by the CDC for persons ≥60 years. We analyzed U.S. reports of adverse events (AEs) following ZVL submitted to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system to monitor vaccine safety, for persons vaccinated May 1, 2006, through January 31, 2015. We conducted descriptive analysis, clinical reviews of reports with selected pre-specified conditions, and empirical Bayesian data mining. VAERS received 23,092 reports following ZVL, of which 22,120 (96%) were classified as non-serious. Of reports where age was documented (n = 18,817), 83% were in persons aged ≥60 years. Reporting rates of AEs were 106 and 4.4 per 100,000 ZVL doses distributed for all reports and serious reports, respectively. When ZVL was administered alone among persons aged ≥50 years, injection site erythema (27%), HZ (17%), injection site swelling (17%), and rash (14%) were the most commonly reported symptoms among non-serious reports; HZ (29%), pain (18%), and rash (16%) were the most commonly reported symptoms among serious reports. Six reports included laboratory evidence of vaccine-strain varicella-zoster virus (Oka/Merck strain) infection; AEs included HZ, HZ- or varicella-like illness, and local reaction with vesicles. In our review of reports of death with sufficient information to determine cause (n = 46, median age 75 years), the most common causes were heart disease (n = 28), sepsis (n = 4), and stroke (n = 3). Empirical Bayesian data mining did not detect new or unexpected safety signals. Findings from our safety review of ZVL are consistent with those from pre-licensure clinical trials and other post-licensure assessments. Transient injection-site reactions, HZ, and rashes were most frequently

Cytomegalovirus seropositivity is associated with herpes zoster

PubMed Central

Ogunjimi, Benson; Hens, Niel; Pebody, Richard; Jansens, Hilde; Seale, Holly; Quinlivan, Mark; Theeten, Heidi; Goossens, Herman; Breuer, Judy; Beutels, Philippe

2015-01-01

Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively recruited ambulatory adult HZ patients in the UK (N = 223) in order to compare the results with those from UK population samples (N = 1545) by means of a logistic regression (controlling for age and gender). Furthermore, we compared the UK population CMV seroprevalence with those from population samples from other countries (from Belgium (N1 = 1741, N2 = 576), USA (N = 5572) and Australia (N = 2080)). Furthermore, CMV IgG titers could be compared between UK HZ patients and Belgium N2 population samples because the same experimental set-up for analysis was used. We found UK ambulatory HZ patients to have a higher CMV seroprevalence than UK population samples (OR 1.56 [1.11 2.19]). CMV IgG seropositivity was a significant risk factor for HZ in the UK (OR 3.06 [1.32 7.04]. Furthermore, high CMV IgG titers (exceeding the upper threshold) were less abundant in CMV-seropositive Belgian N2 population samples than in CMV-seropositive UK HZ patients (OR 0.51 [0.31 0.82]. We found CMV-seroprevalence to increase faster with age in the UK than in other countries (P < 0.05). We conclude that CMV IgG seropositivity is associated with HZ. This finding could add to the growing list of risk factors for HZ. PMID:25905443

New insights into protein-protein interaction data lead to increased estimates of the S. cerevisiae interactome size.

PubMed

Sambourg, Laure; Thierry-Mieg, Nicolas

2010-12-21

As protein interactions mediate most cellular mechanisms, protein-protein interaction networks are essential in the study of cellular processes. Consequently, several large-scale interactome mapping projects have been undertaken, and protein-protein interactions are being distilled into databases through literature curation; yet protein-protein interaction data are still far from comprehensive, even in the model organism Saccharomyces cerevisiae. Estimating the interactome size is important for evaluating the completeness of current datasets, in order to measure the remaining efforts that are required. We examined the yeast interactome from a new perspective, by taking into account how thoroughly proteins have been studied. We discovered that the set of literature-curated protein-protein interactions is qualitatively different when restricted to proteins that have received extensive attention from the scientific community. In particular, these interactions are less often supported by yeast two-hybrid, and more often by more complex experiments such as biochemical activity assays. Our analysis showed that high-throughput and literature-curated interactome datasets are more correlated than commonly assumed, but that this bias can be corrected for by focusing on well-studied proteins. We thus propose a simple and reliable method to estimate the size of an interactome, combining literature-curated data involving well-studied proteins with high-throughput data. It yields an estimate of at least 37, 600 direct physical protein-protein interactions in S. cerevisiae. Our method leads to higher and more accurate estimates of the interactome size, as it accounts for interactions that are genuine yet difficult to detect with commonly-used experimental assays. This shows that we are even further from completing the yeast interactome map than previously expected.

Photoreactive Stapled BH3 Peptides to Dissect the BCL-2 Family Interactome

PubMed Central

Braun, Craig R.; Mintseris, Julian; Gavathiotis, Evripidis; Bird, Gregory H.; Gygi, Steven P.; Walensky, Loren D.

2010-01-01

SUMMARY Defining protein interactions forms the basis for discovery of biological pathways, disease mechanisms, and opportunities for therapeutic intervention. To harness the robust binding affinity and selectivity of structured peptides for interactome discovery, we engineered photoreactive stapled BH3 peptide helices that covalently capture their physiologic BCL-2 family targets. The crosslinking α-helices covalently trap both static and dynamic protein interactors, and enable rapid identification of interaction sites, providing a critical link between interactome discovery and targeted drug design. PMID:21168768

[Vaccines against Herpes zoster: Effectiveness, safety, and cost/benefit ratio].

PubMed

Ferahta, Nabila; Achek, Imene; Dubourg, Julie; Lang, Pierre-Olivier

2016-02-01

A vaccination against herpes zoster and its complication is available in France since June 2015. Its exact benefit for public health is still controversial and its level of protection is not optimal. All those reasons seem to suggest a low acceptation rate from general practitioners. To evaluate the effectiveness, the safety, and the cost/benefit ratio of the vaccination against herpes zoster in people aged 50 year or over. Systematic review in Medline and PubMed with research by key words: "herpes zoster vaccine", "zoster vaccine" and "post herpetic neuralgia vaccine". Randomized and observational studies published in English and French language have been selected by two readers. On 1886 articles identified, 62 studies were included in this systematic review of which 21 randomized trials, 21 observational studies, and 17 medico-economic studies concerned the unadjuvanted vaccine. Considered studies showed an effectiveness of 50% against herpes zoster and 60% on post-herpetic neuralgia incidence of the unadjuvanted vaccine. Five randomized controlled studies were identified for the adjuvanted vaccine. The overall effectiveness of this vaccine was > 90% whatever the age of subjects including those over age 70 and 80. The medico-economic studies conducted in many countries have shown that vaccine policies were beneficial in individuals aged 60 years or over. Most of data of effectiveness, and tolerance result from 2 large controlled studies only (SPS and ZEST) for the unadjuvanted vaccine and only one for the adjuvanted vaccine. Despite controversy and few uncertainties, the vaccine significantly reduces herpes zoster and its complication incidence. In terms of public health objectives, it reduces the burden of the disease and has a positive medico-economic impact. Preliminary data concerning the adjuvanted vaccine, whilst very promising, are still too limited. Up to now, no group of people with particularly high risk of herpes zoster-related complication who will

Receptor Tyrosine Kinase MET Interactome and Neurodevelopmental Disorder Partners at the Developing Synapse.

PubMed

Xie, Zhihui; Li, Jing; Baker, Jonathan; Eagleson, Kathie L; Coba, Marcelo P; Levitt, Pat

2016-12-15

Atypical synapse development and plasticity are implicated in many neurodevelopmental disorders (NDDs). NDD-associated, high-confidence risk genes have been identified, yet little is known about functional relationships at the level of protein-protein interactions, which are the dominant molecular bases responsible for mediating circuit development. Proteomics in three independent developing neocortical synaptosomal preparations identified putative interacting proteins of the ligand-activated MET receptor tyrosine kinase, an autism risk gene that mediates synapse development. The candidates were translated into interactome networks and analyzed bioinformatically. Additionally, three independent quantitative proximity ligation assays in cultured neurons and four independent immunoprecipitation analyses of synaptosomes validated protein interactions. Approximately 11% (8/72) of MET-interacting proteins, including SHANK3, SYNGAP1, and GRIN2B, are associated with NDDs. Proteins in the MET interactome were translated into a novel MET interactome network based on human protein-protein interaction databases. High-confidence genes from different NDD datasets that encode synaptosomal proteins were analyzed for being enriched in MET interactome proteins. This was found for autism but not schizophrenia, bipolar disorder, major depressive disorder, or attention-deficit/hyperactivity disorder. There is correlated gene expression between MET and its interactive partners in developing human temporal and visual neocortices but not with highly expressed genes that are not in the interactome. Proximity ligation assays and biochemical analyses demonstrate that MET-protein partner interactions are dynamically regulated by receptor activation. The results provide a novel molecular framework for deciphering the functional relations of key regulators of synaptogenesis that contribute to both typical cortical development and to NDDs. Copyright © 2016 Society of Biological Psychiatry

Herpes zoster vaccine: A health economic evaluation for Switzerland.

PubMed

Blank, Patricia R; Ademi, Zanfina; Lu, Xiaoyan; Szucs, Thomas D; Schwenkglenks, Matthias

2017-07-03

Herpes zoster (HZ) or "shingles" results from a reactivation of the varicella zoster virus (VZV) acquired during primary infection (chickenpox) and surviving in the dorsal root ganglia. In about 20% of cases, a complication occurs, known as post-herpetic neuralgia (PHN). A live attenuated vaccine against VZV is available for the prevention of HZ and subsequent PHN. The present study aims to update an earlier evaluation estimating the cost-effectiveness of the HZ vaccine from a Swiss third party payer perspective. It takes into account updated vaccine prices, a different age cohort, latest clinical data and burden of illness data. A Markov model was developed to simulate the lifetime consequences of vaccinating 15% of the Swiss population aged 65-79 y. Information from sentinel data, official statistics and published literature were used. Endpoints assessed were number of HZ and PHN cases, quality-adjusted life years (QALYs), costs of hospitalizations, consultations and prescriptions. Based on a vaccine price of CHF 162, the vaccination strategy accrued additional costs of CHF 17,720,087 and gained 594 QALYs. The incremental cost-effectiveness ratio (ICER) was CHF 29,814 per QALY gained. Sensitivity analyses showed that the results were most sensitive to epidemiological inputs, utility values, discount rates, duration of vaccine efficacy, and vaccine price. Probabilistic sensitivity analyses indicated a more than 99% chance that the ICER was below 40,000 CHF per QALY. Findings were in line with existing cost-effectiveness analyses of HZ vaccination. This updated study supports the value of an HZ vaccination strategy targeting the Swiss population aged 65-79 y.

A highly efficient approach to protein interactome mapping based on collaborative filtering framework.

PubMed

Luo, Xin; You, Zhuhong; Zhou, Mengchu; Li, Shuai; Leung, Hareton; Xia, Yunni; Zhu, Qingsheng

2015-01-09

The comprehensive mapping of protein-protein interactions (PPIs) is highly desired for one to gain deep insights into both fundamental cell biology processes and the pathology of diseases. Finely-set small-scale experiments are not only very expensive but also inefficient to identify numerous interactomes despite their high accuracy. High-throughput screening techniques enable efficient identification of PPIs; yet the desire to further extract useful knowledge from these data leads to the problem of binary interactome mapping. Network topology-based approaches prove to be highly efficient in addressing this problem; however, their performance deteriorates significantly on sparse putative PPI networks. Motivated by the success of collaborative filtering (CF)-based approaches to the problem of personalized-recommendation on large, sparse rating matrices, this work aims at implementing a highly efficient CF-based approach to binary interactome mapping. To achieve this, we first propose a CF framework for it. Under this framework, we model the given data into an interactome weight matrix, where the feature-vectors of involved proteins are extracted. With them, we design the rescaled cosine coefficient to model the inter-neighborhood similarity among involved proteins, for taking the mapping process. Experimental results on three large, sparse datasets demonstrate that the proposed approach outperforms several sophisticated topology-based approaches significantly.

A Highly Efficient Approach to Protein Interactome Mapping Based on Collaborative Filtering Framework

PubMed Central

Luo, Xin; You, Zhuhong; Zhou, Mengchu; Li, Shuai; Leung, Hareton; Xia, Yunni; Zhu, Qingsheng

2015-01-01

The comprehensive mapping of protein-protein interactions (PPIs) is highly desired for one to gain deep insights into both fundamental cell biology processes and the pathology of diseases. Finely-set small-scale experiments are not only very expensive but also inefficient to identify numerous interactomes despite their high accuracy. High-throughput screening techniques enable efficient identification of PPIs; yet the desire to further extract useful knowledge from these data leads to the problem of binary interactome mapping. Network topology-based approaches prove to be highly efficient in addressing this problem; however, their performance deteriorates significantly on sparse putative PPI networks. Motivated by the success of collaborative filtering (CF)-based approaches to the problem of personalized-recommendation on large, sparse rating matrices, this work aims at implementing a highly efficient CF-based approach to binary interactome mapping. To achieve this, we first propose a CF framework for it. Under this framework, we model the given data into an interactome weight matrix, where the feature-vectors of involved proteins are extracted. With them, we design the rescaled cosine coefficient to model the inter-neighborhood similarity among involved proteins, for taking the mapping process. Experimental results on three large, sparse datasets demonstrate that the proposed approach outperforms several sophisticated topology-based approaches significantly. PMID:25572661

A Highly Efficient Approach to Protein Interactome Mapping Based on Collaborative Filtering Framework

NASA Astrophysics Data System (ADS)

Luo, Xin; You, Zhuhong; Zhou, Mengchu; Li, Shuai; Leung, Hareton; Xia, Yunni; Zhu, Qingsheng

2015-01-01

The comprehensive mapping of protein-protein interactions (PPIs) is highly desired for one to gain deep insights into both fundamental cell biology processes and the pathology of diseases. Finely-set small-scale experiments are not only very expensive but also inefficient to identify numerous interactomes despite their high accuracy. High-throughput screening techniques enable efficient identification of PPIs; yet the desire to further extract useful knowledge from these data leads to the problem of binary interactome mapping. Network topology-based approaches prove to be highly efficient in addressing this problem; however, their performance deteriorates significantly on sparse putative PPI networks. Motivated by the success of collaborative filtering (CF)-based approaches to the problem of personalized-recommendation on large, sparse rating matrices, this work aims at implementing a highly efficient CF-based approach to binary interactome mapping. To achieve this, we first propose a CF framework for it. Under this framework, we model the given data into an interactome weight matrix, where the feature-vectors of involved proteins are extracted. With them, we design the rescaled cosine coefficient to model the inter-neighborhood similarity among involved proteins, for taking the mapping process. Experimental results on three large, sparse datasets demonstrate that the proposed approach outperforms several sophisticated topology-based approaches significantly.

Herpes Zoster Immunization in Older Adults Has Big Benefits.

PubMed

Breivik, Harald

2015-09-01

A case of acute herpes zoster neuralgia (shingles) in a 78-year-old patient is described. The value and importance of immunizing against herpes zoster to decrease the incidence and severity of both acute herpes zoster neuralgia and postherpetic neuralgia are described. --This report is adapted from paineurope 2015: Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be viewed via the Web site: www.paineurope.com , at which health professionals can find links to the original articles and request copies of the quarterly publication and access additional pain education and pain management resources.

Contacts with children and young people and adult risk of suffering herpes zoster.

PubMed

Salleras, M; Domínguez, A; Soldevila, N; Prat, A; Garrido, P; Torner, N; Borrás, E; Salleras, L

2011-10-13

We carried out a matched case-control study to analyze the possible association between exposure to the children and the risk of suffering herpes-zoster in adulthood. Cases of herpes zoster in immunocompetent healthy patients aged ≥ 25 years seen in the dermatology department of the Sagrado Corazón Hospital in 2007-2008 were matched with four controls. Data were analyzed using conditional logistic regression. 153 cases and 604 matched controls were included. Contacts with children were significantly associated with a reduction in the risk of suffering herpes zoster in adulthood (adjusted OR 0.56 [0.37-0.85]). Herpes-zoster vaccination in immunocompetent people aged ≥ 50 years could counteract the possible negative effects of mass varicella vaccination in childhood on the epidemiology of herpes zoster in adults. Copyright © 2011 Elsevier Ltd. All rights reserved.

Serial interactome capture of the human cell nucleus.

PubMed

Conrad, Thomas; Albrecht, Anne-Susann; de Melo Costa, Veronica Rodrigues; Sauer, Sascha; Meierhofer, David; Ørom, Ulf Andersson

2016-04-04

Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present 'serial RNA interactome capture' (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)-RNA-protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA-RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs.

Latent Virus Reactivation in Astronauts and Shingles Patients

NASA Technical Reports Server (NTRS)

Mehta, Satish K.; Cohrs, Randall J.; Gilden, Donald H.; Tyring, Stephen K.; Castro, Victoria A.; Ott, C. Mark; Pierson, Duane L.

2010-01-01

Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpesviruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpes viruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

Hospitalizations realted to herpes zoster infection in the Canary Islands, Spain (2005-2014).

PubMed

García-Rojas, Amós; Gil-Prieto, Ruth; Núñez-Gallo, Domingo Ángel; Matute-Cruz, Petra; Gil-de-Miguel, Angel

2017-08-24

Herpes zoster is an important problem of public health especially among the elderly in Spain. A population-based retrospective epidemiological study to estimate the burden of herpes zoster requiring hospitalization in the Canary Islands, Spain was conducted by using data from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos. Records of all patients admitted to hospital with a diagnosis of herpes zoster in any position and cases of primary diagnosis (ICD-9-MC codes 053.0-053.9) during a 10-year period (2005-2014), were selected. A total of 1088 hospitalizations with a primary or secondary diagnosis of herpes zoster were identified during the study period. Annually there were 6.99 hospitalizations by herpes zoster per 100,000 population. It increases with age reaching a maximum in persons ≥85 years of age (43.98 admissions per 100,000). Average length of hospitalization was 16 days and 73 patients died, with a case-fatality rate of 4.03%. In 22% of the cases hospitalized, herpes zoster was the primary diagnosis. The hospitalization burden of herpes zoster in adults in the Canary Islands was still important during the last decade and justify the implementation of preventive measures, like vaccination in the elderly or other high risk groups to reduce the most severe cases of the disease.

Herpes zoster-associated voiding dysfunction in hematopoietic malignancy patients.

PubMed

Imafuku, Shinichi; Takahara, Masakazu; Uenotsuchi, Takeshi; Iwato, Koji; Furue, Masutaka

2008-01-01

Voiding dysfunction is a rare but important complication of lumbo-sacral herpes zoster. Although the symptoms are transient, the clinical impact on immunocompromised patients cannot be overlooked. To clarify the time course of voiding dysfunction in herpes zoster, 13 herpes zoster patients with voiding dysfunction were retrospectively analyzed. Of 13 patients, 12 had background disease, and six of these were hematopoietic malignancies; four of these patients were hematopoietic stem cell transplant (HSCT) recipients. Ten patients had sacral lesions, two had lumbar, and one had thoracic lesions. Interestingly, patients with severe rash, or with hematopoietic malignancy had later onset of urinary retention than did patients with mild skin symptoms (Mann-Whitney U analysis, P = 0.053) or with other background disease (P = 0.0082). Patients with severe skin rash also had longer durations (P = 0.035). In one case, acute urinary retention occurred as late as 19 days after the onset of skin rash. In immune compromised subjects, attention should be paid to patients with herpes zoster in the lumbo-sacral area for late onset of acute urinary retention even after the resolution of skin symptoms.

A systematic review and meta-analysis on herpes zoster and the risk of cardiac and cerebrovascular events.

PubMed

Erskine, Nathaniel; Tran, Hoang; Levin, Leonard; Ulbricht, Christine; Fingeroth, Joyce; Kiefe, Catarina; Goldberg, Robert J; Singh, Sonal

2017-01-01

Patients who develop herpes zoster or herpes zoster ophthalmicus may be at risk for cerebrovascular and cardiac complications. We systematically reviewed the published literature to determine the association between herpes zoster and its subtypes with the occurrence of cerebrovascular and cardiac events. Systematic searches of PubMed (MEDLINE), SCOPUS (Embase) and Google Scholar were performed in December 2016. Eligible studies were cohort, case-control, and self-controlled case-series examining the association between herpes zoster or subtypes of herpes zoster with the occurrence of cerebrovascular and cardiac events including stroke, transient ischemic attack, coronary heart disease, and myocardial infarction. Data on the occurrence of the examined events were abstracted. Odds ratios and their accompanying confidence intervals were estimated using random and fixed effects models with statistical heterogeneity estimated with the I2 statistic. Twelve studies examining 7.9 million patients up to 28 years after the onset of herpes zoster met our pre-defined eligibility criteria. Random and fixed effects meta-analyses showed that herpes zoster, type unspecified, and herpes zoster ophthalmicus were associated with a significantly increased risk of cerebrovascular events, without any evidence of statistical heterogeneity. Our meta-analysis also found a significantly increased risk of cardiac events associated with herpes zoster, type unspecified. Our results are consistent with the accumulating body of evidence that herpes zoster and herpes zoster ophthalmicus are significantly associated with cerebrovascular and cardiovascular events.

Varicella zoster meningitis in a pregnant woman with acquired immunodeficiency syndrome.

PubMed

Jayakrishnan, Asha; Vrees, Roxanne; Anderson, Brenna

2008-10-01

Between 6000 and 7000 women in the United States infected with human immunodeficiency virus (HIV) give birth annually. It is well known that HIV-related immunosuppression significantly increases the risk for acquiring opportunistic infections (OIs). However, there is limited information regarding the relationship of pregnancy in the setting of HIV/AIDS infection, subsequent development of OIs, and maternal and fetal outcomes. A pregnant 36-year-old woman with AIDS was diagnosed with varicella zoster meningitis. Weight-based therapy with acyclovir was initiated with clinical improvement in symptoms. Care of a pregnant HIV-infected patient with an OI poses a unique diagnostic and therapeutic challenge for clinicians. Early diagnosis and initiation of appropriate treatment may provide an opportunity to improve both maternal and fetal outcomes.

SH3 interactome conserves general function over specific form

PubMed Central

Xin, Xiaofeng; Gfeller, David; Cheng, Jackie; Tonikian, Raffi; Sun, Lin; Guo, Ailan; Lopez, Lianet; Pavlenco, Alevtina; Akintobi, Adenrele; Zhang, Yingnan; Rual, Jean-François; Currell, Bridget; Seshagiri, Somasekar; Hao, Tong; Yang, Xinping; Shen, Yun A; Salehi-Ashtiani, Kourosh; Li, Jingjing; Cheng, Aaron T; Bouamalay, Dryden; Lugari, Adrien; Hill, David E; Grimes, Mark L; Drubin, David G; Grant, Barth D; Vidal, Marc; Boone, Charles; Sidhu, Sachdev S; Bader, Gary D

2013-01-01

Src homology 3 (SH3) domains bind peptides to mediate protein–protein interactions that assemble and regulate dynamic biological processes. We surveyed the repertoire of SH3 binding specificity using peptide phage display in a metazoan, the worm Caenorhabditis elegans, and discovered that it structurally mirrors that of the budding yeast Saccharomyces cerevisiae. We then mapped the worm SH3 interactome using stringent yeast two-hybrid and compared it with the equivalent map for yeast. We found that the worm SH3 interactome resembles the analogous yeast network because it is significantly enriched for proteins with roles in endocytosis. Nevertheless, orthologous SH3 domain-mediated interactions are highly rewired. Our results suggest a model of network evolution where general function of the SH3 domain network is conserved over its specific form. PMID:23549480

Deriving Heterospecific Self-Assembling Protein-Protein Interactions Using a Computational Interactome Screen.

PubMed

Crooks, Richard O; Baxter, Daniel; Panek, Anna S; Lubben, Anneke T; Mason, Jody M

2016-01-29

Interactions between naturally occurring proteins are highly specific, with protein-network imbalances associated with numerous diseases. For designed protein-protein interactions (PPIs), required specificity can be notoriously difficult to engineer. To accelerate this process, we have derived peptides that form heterospecific PPIs when combined. This is achieved using software that generates large virtual libraries of peptide sequences and searches within the resulting interactome for preferentially interacting peptides. To demonstrate feasibility, we have (i) generated 1536 peptide sequences based on the parallel dimeric coiled-coil motif and varied residues known to be important for stability and specificity, (ii) screened the 1,180,416 member interactome for predicted Tm values and (iii) used predicted Tm cutoff points to isolate eight peptides that form four heterospecific PPIs when combined. This required that all 32 hypothetical off-target interactions within the eight-peptide interactome be disfavoured and that the four desired interactions pair correctly. Lastly, we have verified the approach by characterising all 36 pairs within the interactome. In analysing the output, we hypothesised that several sequences are capable of adopting antiparallel orientations. We subsequently improved the software by removing sequences where doing so led to fully complementary electrostatic pairings. Our approach can be used to derive increasingly large and therefore complex sets of heterospecific PPIs with a wide range of potential downstream applications from disease modulation to the design of biomaterials and peptides in synthetic biology. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Is ultra-violet radiation the main force shaping molecular evolution of varicella-zoster virus?

PubMed Central

2011-01-01

Background Varicella (chickenpox) exhibits a characteristic epidemiological pattern which is associated with climate. In general, primary infections in tropical regions are comparatively less frequent among children than in temperate regions. This peculiarity regarding varicella-zoster virus (VZV) infection among certain age groups in tropical regions results in increased susceptibility during adulthood in these regions. Moreover, this disease shows a cyclic behavior in which the number of cases increases significantly during winter and spring. This observation further supports the participation of environmental factors in global epidemiology of chickenpox. However, the underlying mechanisms responsible for this distinctive disease behavior are not understood completely. In a recent publication, Philip S. Rice has put forward an interesting hypothesis suggesting that ultra-violet (UV) radiation is the major environmental factor driving the molecular evolution of VZV. Discussion While we welcomed the attempt to explain the mechanisms controlling VZV transmission and distribution, we argue that Rice's hypothesis takes lightly the circulation of the so called "temperate VZV genotypes" in tropical regions and, to certain degree, overlooks the predominance of such lineages in certain non-temperate areas. Here, we further discuss and present new information about the overwhelming dominance of temperate VZV genotypes in Mexico regardless of geographical location and climate. Summary UV radiation does not satisfactorily explain the distribution of VZV genotypes in different tropical and temperate regions of Mexico. Additionally, the cyclic behavior of varicella does not shown significant differences between regions with different climates in the country. More studies should be conducted to identify the factors directly involved in viral spreading. A better understanding of the modes of transmissions exploited by VZV and their effect on viral fitness is likely to facilitate

Varicella Zoster Virus-Associated Necrotizing Retinitis After Chickenpox in a 10-Year-Old Female: A Case Report.

PubMed

Shin, Yong Un; Kim, Jihong; Hong, Eun Hee; Kim, Jieun; Sohn, Joo Hyun; Cho, Heeyoon

2017-10-01

A necrotizing retinitis in children is a rare but vision-threatening ocular complication of chickenpox. We report a 10-year-old girl who developed chickenpox 1 month before presenting with panuveitis and necrotizing retinitis. After prompt antiviral treatment, her inflammatory signs were resolved. Early detection and treatment of varicella zoster-associated necrotizing retinitis after chickenpox can achieve good visual outcome.

A systematic review and meta-analysis on herpes zoster and the risk of cardiac and cerebrovascular events

PubMed Central

Erskine, Nathaniel; Tran, Hoang; Levin, Leonard; Ulbricht, Christine; Fingeroth, Joyce; Kiefe, Catarina; Singh, Sonal

2017-01-01

Background Patients who develop herpes zoster or herpes zoster ophthalmicus may be at risk for cerebrovascular and cardiac complications. We systematically reviewed the published literature to determine the association between herpes zoster and its subtypes with the occurrence of cerebrovascular and cardiac events. Methods/Results Systematic searches of PubMed (MEDLINE), SCOPUS (Embase) and Google Scholar were performed in December 2016. Eligible studies were cohort, case-control, and self-controlled case-series examining the association between herpes zoster or subtypes of herpes zoster with the occurrence of cerebrovascular and cardiac events including stroke, transient ischemic attack, coronary heart disease, and myocardial infarction. Data on the occurrence of the examined events were abstracted. Odds ratios and their accompanying confidence intervals were estimated using random and fixed effects models with statistical heterogeneity estimated with the I2 statistic. Twelve studies examining 7.9 million patients up to 28 years after the onset of herpes zoster met our pre-defined eligibility criteria. Random and fixed effects meta-analyses showed that herpes zoster, type unspecified, and herpes zoster ophthalmicus were associated with a significantly increased risk of cerebrovascular events, without any evidence of statistical heterogeneity. Our meta-analysis also found a significantly increased risk of cardiac events associated with herpes zoster, type unspecified. Conclusions Our results are consistent with the accumulating body of evidence that herpes zoster and herpes zoster ophthalmicus are significantly associated with cerebrovascular and cardiovascular events. PMID:28749981

An In Vitro Model of Latency and Reactivation of Varicella Zoster Virus in Human Stem Cell-Derived Neurons

PubMed Central

Markus, Amos; Lebenthal-Loinger, Ilana; Yang, In Hong; Kinchington, Paul R.; Goldstein, Ronald S.

2015-01-01

Varicella zoster virus (VZV) latency in sensory and autonomic neurons has remained enigmatic and difficult to study, and experimental reactivation has not yet been achieved. We have previously shown that human embryonic stem cell (hESC)-derived neurons are permissive to a productive and spreading VZV infection. We now demonstrate that hESC-derived neurons can also host a persistent non-productive infection lasting for weeks which can subsequently be reactivated by multiple experimental stimuli. Quiescent infections were established by exposing neurons to low titer cell-free VZV either by using acyclovir or by infection of axons in compartmented microfluidic chambers without acyclovir. VZV DNA and low levels of viral transcription were detectable by qPCR for up to seven weeks. Quiescently-infected human neuronal cultures were induced to undergo renewed viral gene and protein expression by growth factor removal or by inhibition of PI3-Kinase activity. Strikingly, incubation of cultures induced to reactivate at a lower temperature (34°C) resulted in enhanced VZV reactivation, resulting in spreading, productive infections. Comparison of VZV genome transcription in quiescently-infected to productively-infected neurons using RNASeq revealed preferential transcription from specific genome regions, especially the duplicated regions. These experiments establish a powerful new system for modeling the VZV latent state, and reveal a potential role for temperature in VZV reactivation and disease. PMID:26042814

SPRINT: ultrafast protein-protein interaction prediction of the entire human interactome.

PubMed

Li, Yiwei; Ilie, Lucian

2017-11-15

Proteins perform their functions usually by interacting with other proteins. Predicting which proteins interact is a fundamental problem. Experimental methods are slow, expensive, and have a high rate of error. Many computational methods have been proposed among which sequence-based ones are very promising. However, so far no such method is able to predict effectively the entire human interactome: they require too much time or memory. We present SPRINT (Scoring PRotein INTeractions), a new sequence-based algorithm and tool for predicting protein-protein interactions. We comprehensively compare SPRINT with state-of-the-art programs on seven most reliable human PPI datasets and show that it is more accurate while running orders of magnitude faster and using very little memory. SPRINT is the only sequence-based program that can effectively predict the entire human interactome: it requires between 15 and 100 min, depending on the dataset. Our goal is to transform the very challenging problem of predicting the entire human interactome into a routine task. The source code of SPRINT is freely available from https://github.com/lucian-ilie/SPRINT/ and the datasets and predicted PPIs from www.csd.uwo.ca/faculty/ilie/SPRINT/ .

Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.

PubMed

Li, Jiannong; Bennett, Keiryn; Stukalov, Alexey; Fang, Bin; Zhang, Guolin; Yoshida, Takeshi; Okamoto, Isamu; Kim, Jae-Young; Song, Lanxi; Bai, Yun; Qian, Xiaoning; Rawal, Bhupendra; Schell, Michael; Grebien, Florian; Winter, Georg; Rix, Uwe; Eschrich, Steven; Colinge, Jacques; Koomen, John; Superti-Furga, Giulio; Haura, Eric B

2013-11-05

We hypothesized that elucidating the interactome of epidermal growth factor receptor (EGFR) forms that are mutated in lung cancer, via global analysis of protein-protein interactions, phosphorylation, and systematically perturbing the ensuing network nodes, should offer a new, more systems-level perspective of the molecular etiology. Here, we describe an EGFR interactome of 263 proteins and offer a 14-protein core network critical to the viability of multiple EGFR-mutated lung cancer cells. Cells with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) had differential dependence of the core network proteins based on the underlying molecular mechanisms of resistance. Of the 14 proteins, 9 are shown to be specifically associated with survival of EGFR-mutated lung cancer cell lines. This included EGFR, GRB2, MK12, SHC1, ARAF, CD11B, ARHG5, GLU2B, and CD11A. With the use of a drug network associated with the core network proteins, we identified two compounds, midostaurin and lestaurtinib, that could overcome drug resistance through direct EGFR inhibition when combined with erlotinib. Our results, enabled by interactome mapping, suggest new targets and combination therapies that could circumvent EGFR TKI resistance.

Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster

PubMed Central

Ogunjimi, Benson; Willem, Lander; Beutels, Philippe; Hens, Niel

2015-01-01

Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure ‘opportunities’ through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed. DOI: http://dx.doi.org/10.7554/eLife.07116.001 PMID:26259874

Epidemiological features and costs of herpes zoster in Taiwan: a national study 2000 to 2006.

PubMed

Jih, Jaw-Shyang; Chen, Yi-Ju; Lin, Ming-Wei; Chen, Yu-Chun; Chen, Tzeng-Ji; Huang, Yu-Lin; Chen, Chih-Chiang; Lee, Ding-Dar; Chang, Yun-Ting; Wang, Wen-Jen; Liu, Han-Nan

2009-11-01

To analyse the epidemiological characteristics and related costs of herpes zoster in Taiwan, a nationally representative cohort of 1,000,000 individuals from the National Health Insurance register was followed up from 2000 to 2006 and their claims data analysed. Overall, 34,280 patients were diagnosed with zoster (incidence 4.89/1000 person-years) and 2944 patients (8.6%) developed post-herpetic neuralgia 3 months after the start of the zoster rash (incidence 0.42/1000 person-years). People with older age, diabetes, and immunocompromising conditions were at higher risk of developing zoster and post-herpetic neuralgia. The overall hospitalization rate for zoster was 16.1 cases per 100,000 person-years. The cost for each home care case and per hospitalized case were approximately 53.30 euro and 1224.70 euro, respectively. Further research into the cost-effectiveness of zoster vaccine is needed.

Intracellular localization of varicella-zoster virus ORF39 protein and its functional relationship to glycoprotein K

DOE Office of Scientific and Technical Information (OSTI.GOV)

Govero, Jennifer; Hall, Susan; Heineman, Thomas C.

2007-02-20

Varicella-zoster virus (VZV) encodes two multiply inserted membrane proteins, open reading frame (ORF) 39 protein (ORF39p) and glycoprotein K (gK). The HSV-1 homologs of these proteins are believed to act in conjunction with each other during viral egress and cell-cell fusion, and they directly influence each other's intracellular trafficking. However, ORF39p and VZV gK have received very limited study largely due to difficulties in producing antibodies to these highly hydrophobic proteins. To overcome this obstacle, we introduced epitope tags into both ORF39p and gK and examined their intracellular distributions in transfected and infected cells. Our data demonstrate that both ORF39pmore » and gK accumulate predominately in the ER of cultured cells when expressed in the absence of other VZV proteins or when coexpressed in isolation from other VZV proteins. Therefore, the transport of VZV ORF39p and gK does not exhibit the functional interdependence seen in their HSV-1 homologs. However, during infection, the primary distributions of ORF39p and gK shift from the ER to the Golgi, and they are also found in the plasma membrane indicating that their intracellular trafficking during infection depends on other VZV-encoded proteins. During infection, ORF39p and gK tightly colocalize with VZV envelope glycoproteins B, E and H; however, the coexpression of ORF39p or gK with other individual viral glycoproteins is insufficient to alter the transport of either ORF39p or gK.« less

Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grose, C.; Jackson, W.; Traugh, J.A.

1989-09-01

Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an inmore » vitro assay containing ({gamma}-{sup 32}P)ATP. The same glycoprotein was phosphorylated when ({sup 32}P)GTP was substituted for ({sup 32}P)ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein.« less

Evaluation of immunity to varicella zoster virus with a novel double antigen sandwich enzyme-linked immunosorbent assay.

PubMed

Liu, Jian; Chen, Chunye; Zhu, Rui; Ye, Xiangzhong; Jia, Jizong; Yang, Lianwei; Wang, Yongmei; Wang, Wei; Ye, Jianghui; Li, Yimin; Zhu, Hua; Zhao, Qinjian; Zhang, Jun; Cheng, Tong; Xia, Ningshao

2016-11-01

Varicella is a highly contagious disease caused by primary infection of Varicella zoster virus (VZV). Varicella can be severe or even lethal in susceptible adults, immunocompromised patients and neonates. Determination of the status of immunity to VZV is recommended for these high-risk populations. Furthermore, measurement of population immunity to VZV can help in developing proper varicella vaccination programmes. VZV glycoprotein E (gE) is an antigen that has been demonstrated to be a highly accurate indicator of VZV-specific immunity. In this study, recombinant gE (rgE) was used to establish a double antigen sandwich enzyme-linked immunosorbent assay (ELISA). The established sandwich ELISA showed high specificity and sensitivity in the detection of human sera, and it could detect VZV-specific antibodies at a concentration of 11.25 m IU/mL with a detection linearity interval of 11.25 to 360 m IU/mL (R 2  = 0.9985). The double gE antigen sandwich ELISA showed a sensitivity of 95.08 % and specificity of 100 % compared to the fluorescent-antibody-to-membrane-antigen (FAMA) test, and it showed a sensitivity of 100 % and a specificity of 94.74 % compared to a commercial neutralizing antibody detection kit. Thus, the established double antigen sandwich ELISA can be used as a sensitive and specific quantitative method to evaluate immunity to VZV.

How perfect can protein interactomes be?

PubMed

Levy, Emmanuel D; Landry, Christian R; Michnick, Stephen W

2009-03-03

Any engineered device should certainly not contain nonfunctional components, for this would be a waste of energy and money. In contrast, evolutionary theory tells us that biological systems need not be optimized and may very well accumulate nonfunctional elements. Mutational and demographic processes contribute to the cluttering of eukaryotic genomes and transcriptional networks with "junk" DNA and spurious DNA binding sites. Here, we question whether such a notion should be applied to protein interactomes-that is, whether these protein interactomes are expected to contain a fraction of nonselected, nonfunctional protein-protein interactions (PPIs), which we term "noisy." We propose a simple relationship between the fraction of noisy interactions expected in a given organism and three parameters: (i) the number of mutations needed to create and destroy interactions, (ii) the size of the proteome, and (iii) the fitness cost of noisy interactions. All three parameters suggest that noisy PPIs are expected to exist. Their existence could help to explain why PPIs determined from large-scale studies often lack functional relationships between interacting proteins, why PPIs are poorly conserved across organisms, and why the PPI space appears to be immensely large. Finally, we propose experimental strategies to estimate the fraction of evolutionary noise in PPI networks.

Incidence and clinical features of herpes simplex viruses (1 and 2) and varicella-zoster virus infections in an adult Korean population with aseptic meningitis or encephalitis.

PubMed

Choi, Rihwa; Kim, Gyeong-Moon; Jo, Ik Joon; Sim, Min Seob; Song, Keun Jeong; Kim, Byoung Joon; Na, Duk L; Huh, Hee Jae; Kim, Jong-Won; Ki, Chang-Seok; Lee, Nam Yong

2014-06-01

Since there are limited data on the incidence and clinical findings of central nervous system (CNS) infection by three α-herpesviruses including human herpes simplex virus 1 (HSV-1), HSV-2 and varicella-zoster virus (VZV) in Korea, a retrospective analysis of clinical data and polymerase chain reaction (PCR) results was performed in patients who presented with suspicion of acute viral meningitis and/or encephalitis at the emergency department of a tertiary referral hospital in Seoul, Korea. During the 3-year study period, a total of 224 cerebrospinal fluid (CSF) samples from 224 patients were examined. Among the 224 patients, 135 (60.3%) patients were identified as having aseptic meningitis (n = 70, 51.9%), encephalitis (n = 41, 30.4%) or meningoencephalitis (n = 24, 17.8%) at discharge. Twenty-four (17.8%) patients were identified as having VZV meningitis (n = 16, 11.9%), VZV meningoencephalitis (n = 2, 1.5%), HSV-2 meningitis (n = 4, 3.0%), or HSV-1 encephalitis (n = 2, 1.5%). Of the 24 patients infected with the three herpesviruses, immunocompromised patients accounted for 33.3% (n = 8). Skin rashes were observed in half (n = 9) of the patients with VZV, and none with HSV-1 or HSV-2. One patient with VZV meningitis and four patients with brain parenchymal involvement had neurologic sequelae. In conclusion, three herpesviruses are important causative agents of CNS infectious disease with significant morbidity in adults, regardless of the immunologic status. Therefore, CSF should be examined for HSV-1, HSV-2, and VZV using sensitive diagnostic methods in all cases of adult patients with clinical manifestations of CNS disease in order to identify the correct etiology and to determine appropriate therapy. © 2014 Wiley Periodicals, Inc.

Immunogenicity and safety of zoster vaccine live administered with quadrivalent influenza virus vaccine.

PubMed

Levin, Myron J; Buchwald, Ulrike K; Gardner, Julie; Martin, Jason; Stek, Jon E; Brown, Elizabeth; Popmihajlov, Zoran

2018-01-02

Randomized, blinded, placebo-controlled trial to evaluate the safety and immunogenicity of ZOSTAVAX™ (ZV) administered concomitantly with quadrivalent inactivated influenza vaccine (IIV4) in adults≥50years of age (NCT02519855). Overall, 440 participants were randomized into the Concomitant Group (CG) and 442 into the Sequential Group (SG). The CG received ZV and IIV4 at separate injection sites on Day 1 and matching placebo at Week 4. The SG received placebo and IIV4 (2015-2016 influenza season) at separate injection sites on Day 1 and ZV at Week 4. Varicella-zoster virus (VZV) antibody geometric mean titer (GMT) and geometric mean fold-rise (GMFR) from baseline to 4weeks postvaccination, measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) and adjusted for age and prevaccination titer. Influenza strain-specific GMT at baseline and 4weeks postvaccination was measured by hemagglutination inhibition (HAI) assay. Injection-site and systemic adverse experiences (AEs) within 28days following any vaccination and serious AEs throughout the study. The adjusted VZV antibody GMT ratio (CG/SG) was 0.87 (95%CI: 0.80, 0.95), meeting the prespecified noninferiority criterion. The VZV antibody GMFR in the CG was 1.9 (95%CI: 1.76, 2.05), meeting the acceptability criterion. Influenza antibody GMT ratios for A/H1N1, A/H3N2, B/Yamagata and B/Victoria were 1.02 (95%CI: 0.88, 1.18), 1.10 (95%CI: 0.94, 1.29), 1.00 (95%CI: 0.88, 1.14), and 0.99 (95%CI: 0.87, 1.13), respectively. The frequency of vaccine-related injection-site and systemic AEs was comparable between groups. No vaccine-related serious AE was observed. The concomitant administration of ZV and IIV4 to adults≥50years of age induced VZV-specific and influenza-specific antibody responses that were comparable to those following administration of either vaccine alone, and was generally well tolerated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reducing pain in acute herpes zoster with plain occlusive dressings: a case report.

PubMed

Keegan, David A

2015-04-25

The pain of acute herpes zoster (shingles) is severe and difficult to control. The medications used to control pain have a variety of important and potentially serious side effects. To the best of my knowledge, this is the first case report of using a plain topical occlusive dressing to reduce the pain of herpes zoster, avoiding the use of medication. A 40-year-old Caucasian man and a qualified physician (the author), developed a dermatomal vesicular rash consistent with herpes zoster. Applying plain topical occlusive dressings reduced the severity of his pain to an ignorable level. Plain topical occlusive dressings provide effective pain relief for acute herpes zoster, thereby avoiding the risks accompanying medication use.