| Varicella zoster virus | |
|---|---|
_Virus_PHIL_1878_lores.jpg) | |
| Electron micrograph of aHuman alphaherpesvirus 3 virion | |
Virus classification | |
| (unranked): | Virus |
| Realm: | Duplodnaviria |
| Kingdom: | Heunggongvirae |
| Phylum: | Peploviricota |
| Class: | Herviviricetes |
| Order: | Herpesvirales |
| Family: | Orthoherpesviridae |
| Genus: | Varicellovirus |
| Species: | Varicellovirus humanalpha3 |
| Synonyms[2] | |
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Varicella zoster virus (VZV), also known ashuman herpesvirus 3 (HHV-3,HHV3), is one of nine knownherpes viruses thatcan infect humans. It causeschickenpox (varicella) commonly affecting children and young adults, andshingles (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 arespecies-specific to humans. The virus can survive in external environments for a few hours.[3]
VZV multiplies in thetonsils, and causes a wide variety of symptoms. Similar to theherpes simplex viruses, after primary infection with VZV (chickenpox), the virus lies dormant inneurons, including thecranial nerve ganglia, dorsal root ganglia, andautonomic ganglia. Many years after the person has recovered from initial chickenpox infection, VZV canreactivate to causeshingles.[4]
Primary varicella zoster virus infection results inchickenpox (varicella), which may result in complications includingencephalitis,pneumonia (either directviral pneumonia or secondarybacterial pneumonia), orbronchitis (either viral bronchitis or secondary bacterial bronchitis). Even when clinical symptoms of chickenpox have resolved, VZV remains dormant in thenervous system of the infected person (virus latency), in thetrigeminal anddorsal root ganglia.[5] VZV enters through therespiratory system and has an incubation period of 10–21 days, with an average of 14 days. Targeting the skin andperipheral nerves, the period of illness lasts about 3 to 4 days. Infected individuals are most contagious 1–2 days before the lesions appear. Signs and symptoms include vesicles that fill with pus, rupture, and scab before healing. Lesions most commonly occur on the face, throat, the lower back, the chest and shoulders.[6]
In about a third of cases,[7] VZV reactivates in later life, producing a disease known asshingles or herpes zoster. The individual lifetime risk of developing herpes zoster is thought to be between 20% and 30%, or approximately 1 in 4 people. However, for people aged 85 and over, this risk increases to 1 in 2.[8]In a study in Sweden by Nilsson et al. (2015) the annual incidence of herpes zoster infection is estimated at a total of 315 cases per 100,000 inhabitants for all ages and 577 cases per 100,000 for people 50 years of age or older.[9]
VZV can also infect thecentral 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.[10]
Shingles lesions and the associated pain, often described as burning, tend to occur on the skin that is innervated by one or two adjacentsensory nerves, 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 aspostherpetic neuralgia. Other serious complications of varicella zoster infection includeMollaret's meningitis, zoster multiplex, and inflammation of arteries in the brain leading tostroke,[11] myelitis, herpes ophthalmicus, or zoster sine herpete. InRamsay Hunt syndrome, VZV affects thegeniculate 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 damaged.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; usingaspirin during infection can increase this risk.[6]
VZV is closely related to theherpes simplex viruses (HSV), sharing much genome homology. The known envelopeglycoproteins (gB, gC, gE, gH, gI, gK, gL) correspond with those in HSV; however, there is no equivalent of the HSV gD protein. VZV also fails to produce the LAT (latency-associated transcripts) that play an important role in establishing HSVlatency (herpes simplex virus).[12] VZV virions are spherical and 180–200 nm in diameter. Their lipidenvelope encloses the 100 nmnucleocapsid of 162hexameric and pentamericcapsomeres arranged in an icosahedral form. ItsDNA is a single, linear, double-stranded molecule, 125,000 nt long. The capsid is surrounded by loosely associated proteins known collectively as the tegument; many of these proteins play critical roles in initiating the process of virus reproduction in the infected cell. The tegument is in turn covered by a lipid envelope studded with glycoproteins that are displayed on the exterior of the virion, each approximately 8 nm long.[13]
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Thegenome was firstsequenced in 1986.[14] It is a linearduplexDNA molecule, a laboratory strain has 124,884base pairs. The genome has two predominantisomers, depending on the orientation of the S segment, P (prototype) and IS (inverted S) which are present with equal frequency for a total frequency of 90–95%. The L segment can also be inverted resulting in a total of four linear isomers (IL and ILS). This is distinct from HSV's equiprobable distribution, and the discriminatory mechanism is not known. A small percentage of isolated molecules arecircular genomes, about which little is known. (It is known that HSV circularizes on infection.) There are at least 70open reading frames in the genome.
| This sectionis missing information about genotype-clade mapping (use existing sources); widespread recombination and clade produced by recombination (use "9geno"); clade 6 (usePMID 25926648). Please expand the section to include this information. Further details may exist on thetalk page.(November 2021) |
Commonality with HSV1 and HSV2 indicates acommon ancestor; five genes (out of about 70) do not have corresponding HSV genes. Relation with other human herpes viruses is less strong, but many homologues andconserved gene blocks are still found.
There are at least fiveclades of this virus.[15] Clades 1 and 3 include European/North American strains; clade 2 are Asian strains, especially from Japan; and clade 5 appears to be based inIndia. 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.[16] 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 targetedsequencing of selected regions.
Phylogenetic analysis of VZV genomic sequences resolves wild-type strains into ninegenotypes (E1, E2, J, M1, M2, M3, M4, VIII and IX).[17][18] 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 foursingle 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.[17] 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.[19]
Themutation rate forsynonymous andnonsynonymous 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.[20]
Within the human body it can be treated by a number of drugs and therapeutic agents includingacyclovir for chickenpox,famciclovir,valaciclovir for the shingles,zoster-immune globulin (ZIG), andvidarabine.[21] Acyclovir is frequently used as the drug of choice in primary VZV infections, and beginning its administration early can significantly shorten the duration of any symptoms. However, reaching an effective serum concentration of acyclovir typically requiresintravenous administration, making its use more difficult outside of a hospital.[22]
A live attenuated VZV Oka/Merck strainvaccine is available and is marketed in the United States under the trade nameVarivax. It was developed byMerck, Sharp & Dohme in the 1980s from the Oka strain virus isolated and attenuated byMichiaki Takahashi and colleagues in the 1970s. It was submitted to the USFood and Drug Administration (FDA) for approval in 1990 and was approved in 1995. Since then, it has been added to the recommended vaccination schedules for children inAustralia, the United States, and many other countries. Varicella vaccination has raised concerns in some that the immunity induced by the vaccine may not be lifelong, possibly leaving adults vulnerable to more severe disease as the immunity from their childhood immunization wanes. Vaccine coverage in the United States in the population recommended for vaccination is approaching 90%, with concomitant reductions in the incidence of varicella cases and hospitalizations and deaths due to VZV.[citation needed] So far, clinical data has proved that the vaccine is effective for over ten years in preventing varicella infection in healthy individuals, and whenbreakthrough infections do occur, illness is typically mild.[23] In 2006, the CDC'sAdvisory Committee on Immunization Practices (ACIP) recommended a second dose of vaccine before school entry to ensure the maintenance of high levels of varicella immunity.[24]
In 2006, the FDA approvedZostavax 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 byCochrane (updated in 2023) shows that Zostavax reduces the incidence of shingles by almost 50%.[25]
Shingrix is asubunit vaccine (HHV3 glycoprotein E) developed byGlaxoSmithKline which was approved in the United States by the FDA in October 2017.[26] 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 twointramuscular doses, two to six months apart.[27] This vaccine has shown to beimmunogenic and safe in adults withhuman immunodeficiency virus.[28]
Chickenpox-like rashes were recognized and described by ancient civilizations; the relationship between zoster and chickenpox was not realized until 1888.[29] In 1943, the similarity between virus particles isolated from the lesions of zoster and those from chickenpox was noted.[30] In 1974 the first chickenpox vaccine was introduced.[31]
The varicella zoster virus was first isolated byEvelyn Nicol while she was working at Cleveland City Hospital.[32]Thomas Huckle Weller also isolated the virus and found evidence that the same virus was responsible for both chickenpox and herpes zoster.[33]
The etymology of the name of the virus comes from the two diseases it causes, varicella and herpes zoster. The wordvaricella is possibly derived fromvariola, a term forsmallpox coined by Rudolph Augustin Vogel in 1764.[34]
Human herpesvirus 3 Human herpesvirus 3 [X04370=NC_001348] (HHV-3) (Varicella-zoster virus)
