Varicella-zoster Virus In Individuals Research Articles

POST HERPETIC NEURALGIA

Postherpetic neuralgia (PHN) is a chronic neuropathic pain condition that lasts 3 months or more after an outbreak of shingles. Herpes zoster, especially acute herpes zoster, is associated with the reactivation of the inactivated varicella zoster virus in individuals who have had chickenpox. PHN is associated with persistent and often refractory neuropathic pain. Patients may experience several types of pain, including deep pain, intolerable pain, burning, paroxysmal pain, stabbing pain, hyperalgesia, and allodynia. Pharmacological treatment of PHN may include a variety of drugs, including alpha-2 delta ligands (gabapentin and pregabalin), other anticonvulsants (carbamazepine), tricyclic antidepressants (amitriptyline, nortriptyline, doxepin), topical analgesics (5% lidocaine patch, capsaicin) tramadol, or other opioids. The sizeable side effect profile of commonly used oral drugs often limits their practical use, and a combination of topical and systemic agents may be required for optimal results. Doctors and other care providers must adapt treatment based on individual patient responses.

GENOTYPING OF VARICELLA-ZOSTER VIRUS (VZV) WILD-TYPE STRAINS ISOLATED IN THE CZECH REPUBLIC

Monitoring of the varicella-zoster virus is becoming an important tool for analysis of the circulation of individual strains of VZV which differ not only at the genomic level, but show a variability in their clinical and epidemiological characteristics. Such data are not available on a large scale from the Czech population and could help understanding the epidemiological and evolutionary characteristics of the virus, as well as its potential for reinfection and increased pathogenesis in the population groups at higher risk for complications. The main aim of this study was detection and monitoring of wild-type or vaccine VZV strain isolates in the region of Eastern Bohemia and genotypic characterization of these isolates. A total of 273 clinical samples were obtained from patients exhibiting symptoms of varicella zoster virus (VZV) infection manifested as chickenpox or herpes zoster (HZ) treated in the Faculty Hospital of Charles University, Medical School in Hradec Kralove, Czech Republic. Characterization of individual short VZV DNA sequences was performed utilizing restriction fragment length polymorphisms (RFLPs), PCR and sequencing. Single nucleotide polymorphisms (SNP) in open reading frames (ORF) 21, 22 and 50 were used to identify individual VZV strains. All clinical isolates (97 from varicella, 176 from herpes zoster) were VZV positive wild-type strains. Sequencing analysis showed that 89 isolates were of the European E1 genotype, 180 were of the European E2 genotype and 2 were identified as the Mosaic M1 strain. In addition, for the first time in this region two unusual genotypes were identified, both representing a combination of E1 and M2 strain specific SNPs. Our prospective VZV genotyping study which is the first to monitor the VZV epidemiological situation in the Czech Republic using such a large set of clinical specimens, has provided valuable epidemiological data and identified two unique VZV recombinants.

Varicella zoster virus vaccines: effective, but concerns linger

Both varicella and herpes zoster (HZ) can cause severe disease in certain age groups. The cell-mediated immune (CMI) response to the varicella zoster virus (VZV) is critical in preventing a recurrence of VZV. The varicella vaccine has markedly decreased the morbidity and mortality associated with varicella, but concerns linger about the cost and frequency of vaccine administration and the long-term effects on both adult varicella and HZ epidemiology in the individual and in the population. Therapy for HZ with an antiviral is only partially effective. A zoster vaccine is now available that boosts the CMI immune reaction to VZV in individuals and has proven safe and partially effective in preventing both HZ and post-herpetic neuralgia. Concerns about the zoster vaccine include the costs of administration, the overall health-care costs to society, and the acceptance and implementation of the vaccine in the elderly. Because of altered immune responses to VZV as a result of universal varicella vaccination it becomes even more compelling in the future to have a zoster vaccine ready to boost the CMI response to a sufficient level to prevent HZ. The 2 vaccines are intertwined in the future epidemiology of VZV disease.

Identification of Viral Antigens Recognized by Ocular Infiltrating T Cells from Patients with Varicella Zoster Virus-Induced Uveitis

Varicella zoster virus (VZV) is a common cause of infectious uveitis associated with an intraocular inflammatory response involving virus-specific T cells. In the current study, the functional characteristics and the antigen specificity of VZV-reactive T cells recovered from intraocular fluid (IOF) samples of five patients with VZV were determined. B-cell lines were infected with a comprehensive panel of recombinant vaccinia viruses expressing 11 individual VZV open reading frames (ORFs), or alternatively pulsed with the corresponding peptides to generate antigen-presenting cells (APCs). T-cell responsiveness of the IOF-derived VZV-specific T cells toward APCs was monitored by interferon (IFN)-gamma enzyme-linked immunosorbent spot-forming assays on bulk T-cell cultures and subsequently T-cell clones (TCCs). The cytokine-secretion profile and cytotoxicity of the VZV-specific TCCs was determined by ELISA and flow cytometry, respectively. T-cell reactivity to VZV proteins encoded by ORF4, -10, -14, -18, -29, -31, -61, -62, -63, -67, and -68 was demonstrated, but specificity varied individually. T-cell epitopes on ORF62 and -68 were delineated. The TCCs secreted IFNgamma, but relatively low levels of interleukin-4 and -5, in response to VZV antigen-expressing APCs. The TCCs induced antigen-specific cytotoxic T-cell activity. The results suggest that the intraocular VZV-specific T-cell response in the patients with VZV analyzed is directed to a broad spectrum of VZV antigens, including the latency-associated VZV proteins from ORFs 4, 29, 63, and particularly ORF62. This local T-cell response was in part mediated by cytotoxic CD4(+) T cells with a Th1/0-like effector memory phenotype.

Genomic analysis of varicella-zoster virus: primers for individual open reading frames.

The genome of varicella-zoster virus (VZV) contains nearly 125,000 bp. Preliminary genomic analysis has revealed that VZV may be less immutable than once thought. Through the investigation of the VZV genome using specifically designed oligonucleotides, it has been learned that sequence variation within VZV open reading frame 62 can distinguish between vaccine and wild-type virus. Additionally, the presence of single nucleotide polymorphisms within the VZV genome has identified distinct VZV populations originating from circumscribed geographic locations. In order for future studies of VZV genetic diversity to be carried out, amplifying and sequencing primers for individual VZV genes have been catalogued. Additionally, this report will facilitate the selection of VZV primers by which to distinguish clinical VZV isolates from vaccinia virus isolates.

The out of Africa model of varicella-zoster virus evolution: single nucleotide polymorphisms and private alleles distinguish Asian clades from European/North American clades

Until 1998, varicella-zoster virus (VZV) was generally considered sufficiently stable to allow the use of a single sequenced virus (VZV-Dumas) as a consensual representation of the world VZV genotype. But recent investigations have uncovered a gE mutant virus called VZV-MSP with a second genotype and a distinguishable accelerated cell spread phenotype. A subsequent study suggested that single nucleotide polymorphisms (SNPs) could be applied toward the genetic analysis of the VZV genome. To further assess the scope of genetic variation in the VZV genome on a worldwide basis, we carried out an extensive SNP analysis of structural glycoprotein genes gB, gE, gH, gI, gL, as well as the IE62 regulatory gene in viruses collected from Western Europe, North America and Asia, including the VZV vaccine strain. The SNP data showed segregation of viral isolates of Asian origin from those of Western ancestry into distinct phylogenetic clades. Unexpectedly, however, VZV from Thailand segregated with VZV from Iceland and the United States, i.e. it was more Western than Asian in nature. Further, SNP analysis disclosed strikingly unusual genotypes, e.g. gH genes with up to five missense mutations and gL genes with insertions of an in-frame methionine codon. In summary, these VZV genomic analyses have shown that individual VZV strains, like closely related human beings, have distinctive SNP profiles containing private alleles within just five VZV genes ( gB, gH, gE, gL and IE62) that provide a fingerprint to localize ancestry of the viral strain.

Recurrent varicella-zoster virus infections in apparently immunocompetent children

Fourteen generally healthy children (5 females, 9 males, ages 18 months to 13 years) who have developed 2 to 5 attacks of chickenpox are described. Herpes zoster also occurred in 2 of 14 children. No case of chickenpox was severe or associated with complications. General studies of immunoglobulins, specific antibodies to immunization agents, complement and lymphocyte subpopulation number and function indicated that 1 of 14 had low serum IgA and 3 of 14 lacked antibody to 1 (n = 2) or 2 (n = 1) immunization agents. Varicella-zoster virus (VZV)-specific immune studies showed that the children developed VZV-antibody titers by enzyme-linked immunosorbent assay of 1:640 to 1:10 240. By immunoblot assay all appeared to develop a normal spectrum of antibodies to individual VZV proteins. All but one developed VZV cellular immune responses with stimulation indices ranging from 3.6 to 174. Sequential follow-up of 8 patients revealed 1 who became seronegative and 2 who lost VZV cell-mediated immune responses. Chickenpox may recur more frequently than is generally recognized. General and VZV-specific immune investigations are unlikely to indicate a reason.