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Varicella zoster virus ( VZV), also known as human herpesvirus 3 ( HHV-3, HHV3), is one of nine known Herpesviridae that can infect humans. It causes chickenpox (varicella), commonly affecting children and young adults, and shingles (herpes zoster) in adults but rarely in children. As a late complication of VZV infection, Ramsay Hunt syndrome type 2 may develop in rare cases. VZV infections are species-specific to humans. The virus can survive in external environments for a few hours.
VZV multiplies in the , and causes a wide variety of symptoms. Similar to the herpes simplex viruses, after primary infection with VZV (chickenpox), the virus lies dormant in Neuron, including the cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia. Many years after the person has recovered from initial chickenpox infection, VZV can Virus latency to cause shingles.
VZV can also infect the central nervous system, with a 2013 article reporting an incidence rate of 1.02 cases per 100,000 inhabitants in Switzerland, and an annual incidence rate of 1.8 cases per 100,000 inhabitants in Sweden.
Shingles lesions and the associated pain, often described as burning, tend to occur on the skin that is innervated by one or two adjacent Sensory nerve, almost always on one side of the body only. The skin lesions usually subside over the course of several weeks, while the pain often persists longer. In 10–15% of cases the pain persists more than three months, a chronic and often disabling condition known as postherpetic neuralgia. Other serious complications of varicella zoster infection include Mollaret's meningitis, zoster multiplex, and inflammation of arteries in the brain leading to stroke, myelitis, herpes ophthalmicus, or zoster sine herpete. In Ramsay Hunt syndrome, VZV affects the geniculate ganglion giving lesions that follow specific branches of the facial nerve. Symptoms may include painful blisters on the tongue and ear along with one-sided facial weakness and hearing loss. After infection during initial stages of pregnancy, the fetus can be severely injured. Reye's syndrome can happen after initial infection, causing continuous vomiting and signs of brain dysfunction such as extreme drowsiness or combative behavior. In some cases, death or coma can follow. Reye's syndrome mostly affects children and teenagers; using aspirin during infection can increase this risk.
There are at least five of this virus. Clades 1 and 3 include European/North American strains; clade 2 are Asian strains, especially from Japan; and clade 5 appears to be based in India. Clade 4 includes some strains from Europe but its geographic origins need further clarification. There are also four genotypes that do not fit into these clades. Allocation of VZV strains to clades required the sequence of whole virus genome. Practically all molecular epidemiological data on global VZV strains distribution are obtained with targeted DNA sequencing of selected regions.
Phylogenetic analysis of VZV genomic sequences resolves wild-type strains into nine Genotype (E1, E2, J, M1, M2, M3, M4, VIII and IX). Complete sequences for M3 and M4 strains are unavailable, but targeted analyses of representative strains suggest they are stable, circulating VZV genotypes. Sequence analysis of VZV isolates identified both shared and specific markers for every genotype and validated a unified VZV genotyping strategy. Despite high genotype diversity no evidence for intra-genotypic recombination was observed. Five of seven VZV genotypes were reliably discriminated using only four single nucleotide polymorphisms (SNP) present in ORF22, and the E1 and E2 genotypes were resolved using SNP located in ORF21, ORF22 or ORF50. Sequence analysis of 342 clinical varicella and zoster specimens from 18 European countries identified the following distribution of VZV genotypes: E1, 221 (65%); E2, 87 (25%); M1, 20 (6%); M2, 3 (1%); M4, 11 (3%). No M3 or J strains were observed. Of 165 clinical varicella and zoster isolates from Australia and New Zealand typed using this approach, 67 of 127 eastern Australian isolates were E1, 30 were E2, 16 were J, 10 were M1, and 4 were M2; 25 of 38 New Zealand isolates were E1, 8 were E2, and 5 were M1.
The mutation rate for synonymous and nonsynonymous mutation rates among the herpesviruses have been estimated at 1 × 10−7 and 2.7 × 10−8 mutations/site/year, respectively, based on the highly conserved gB gene.
In 2006, the FDA approved Zostavax for the prevention of shingles. Zostavax is a more concentrated formulation of the Varivax vaccine, designed to elicit an immune response in older adults whose immunity to VZV wanes with advancing age. A systematic review by Cochrane (updated in 2023) shows that Zostavax reduces the incidence of shingles by almost 50%.
Shingrix is a subunit vaccine (HHV3 glycoprotein E) developed by GlaxoSmithKline which was approved in the United States by the FDA in October 2017. The ACIP recommended Shingrix for adults over the age of 50, including those who have already received Zostavax. The committee voted that Shingrix is preferred over Zostavax for the prevention of zoster and related complications because phase 3 clinical data showed vaccine efficacy of >90% against shingles across all age groups, as well as sustained efficacy over a four-year follow-up. Unlike Zostavax, which is given as a single shot, Shingrix is given as two intramuscular doses, two to six months apart. This vaccine has shown to be Immunogenicity and safe in adults with HIV.
Shingrix vaccine could have protective traits against dementia development. One cohort study from 2025 investigated varicella zoster vaccination with dementia risk. It showed that persons who had received one dose of Shingrix had 11 % lower risk of dementia, compared to unvaccinated. Having received two doses of the vaccine was associated with 32 % decreased risk of dementia, compared to unvaccinated.
The varicella zoster virus was first isolated by Evelyn Nicol while she was working at Cleveland City Hospital. Thomas Huckle Weller also isolated the virus and found evidence that the same virus was responsible for both chickenpox and herpes zoster.
The etymology of the name of the virus comes from the two diseases it causes, varicella and herpes zoster. The word varicella is possibly derived from variola, a term for smallpox coined by Rudolph Augustin Vogel in 1764.
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