Varicella zoster virus
Human alphaherpesvirus 3 (HHV-3), usually referred to as the varicella-zoster virus (VZV), is one of eight herpesviruses known to infect humans. It causes chickenpox (varicella), a disease most commonly affecting children, teens, and young adults, and shingles (herpes zoster) in adults; shingles is rare in children. VZV is a worldwide pathogen known by many names: chickenpox virus, varicella virus, and zoster virus. VZV infections are species-specific to humans, but can survive in external environments for a few hours, maybe a day or two.
|Human alphaherpesvirus 3|
|Electron micrograph of a Human alphaherpesvirus 3 virion|
Human alphaherpesvirus 3
VZV multiplies in the lungs, and causes a wide variety of symptoms. After the primary infection (chickenpox), the virus goes dormant in the nerves, including the cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia. Many years after the person has recovered from chickenpox, VZV can reactivate to cause neurologic conditions.
Primary varicella zoster virus infection results in chickenpox (varicella), which may result in complications including encephalitis, pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), or bronchitis (either viral bronchitis or secondary bacterial bronchitis). Even when clinical symptoms of chickenpox have resolved, VZV remains dormant in the nervous system of the infected person (virus latency), in the trigeminal and dorsal root ganglia. VZV enters through the respiratory system. Having an incubation period of 10–21 days, averaging at 14 days. targeting the skin and peripheral nerve, the period of illness is from 3 to 4 days. 1–2 days before the rashes appear, is when this virus is the most contagious. Some signs and symptoms are vesicles that fill with pus, rupture, and scab before healing. Lesions tend to stay towards the face, throat, and lower back sometimes on the chest and shoulders. Shingles usually stay located around the waist.
In about 10–20% of cases, VZV reactivates later in life, producing a disease known as shingles or herpes zoster. 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.
Other serious complications of varicella zoster infection include postherpetic neuralgia, 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. If infected during initial stages of pregnancy severe damage to the fetus can take place. Reye’s syndrome can happen after initial infection, continuous vomiting and shows signs of brain dysfunction: 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.
This section does not cite any sources. (August 2018) (Learn how and when to remove this template message)
VZV is closely related to the herpes simplex viruses (HSV), sharing much genome homology. The known envelope glycoproteins (gB, gC, gE, gH, gI, gK, gL) correspond with those in HSV; however, there is no equivalent of HSV gD. VZV also fails to produce the LAT (latency-associated transcripts) that play an important role in establishing HSV latency (herpes simplex virus). VZV virons are spherical and 180–200 nm in diameter. Their lipid envelope encloses the 100 nm nucleocapsid of 162 hexameric and pentameric capsomeres arranged in an icosahedral form. Its DNA 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.
The genome was first sequenced in 1986. It is a linear duplex DNA molecule, a laboratory strain has 124,884 base pairs. The genome has 2 predominant isomers, 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 are circular genomes, about which little is known. (It is known that HSV circularizes on infection.) There are at least 70 open reading frames in the genome.
There are at least five clades 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.
Commonality with HSV1 and HSV2 indicates a common ancestor; five genes do not have corresponding HSV genes. Relation with other human herpes viruses is less strong, but many homologues and conserved gene blocks are still found.
There are five principle clades (1–5) and four genotypes that do not fit into these clades. The current distribution of these clades is Asia (clades 1,2, and 5) and Europe (clades 1, 3 and 4). Allocation of VZV strains to clades required sequence of whole virus genome. Practically all molecular epidemiological data on global VZV strains distribution obtained with targeted sequencing of selected regions.
Phylogenetic analysis of VZV genomic sequences resolves wild-type strains into 9 genotypes (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.
Within the human body it can be treated by a number of drugs and therapeutic agents including acyclovir for the chicken pox, famciclovir, valaciclovir for the shingles, zoster-immune globulin (ZIG), and vidarabine. VZV immune globulin is also a treatment. 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 requires intravenous administration, making its use more difficult outside of a hospital.
A live attenuated VZV Oka/Merck strain vaccine is available and is marketed in the United States under the trade name Varivax. It was developed by Merck, Sharp & Dohme in the 1980s from the Oka strain virus isolated and attenuated by Michiaki Takahashi and colleagues in the 1970s. It was submitted to the US Food and Drug Administration for approval in 1990 and was approved in 1995. Since then, it has been added to the recommended vaccination schedules for children in Australia, 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. So far, clinical data has proved that the vaccine is effective for over ten years in preventing varicella infection in healthy individuals, and when breakthrough infections do occur, illness is typically mild. In 2007, the ACIP recommended a second dose of vaccine before school entry to ensure the maintenance of high levels of varicella immunity.
In 2006, the United States Food and Drug Administration 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 the Cochrane Library shows that Zostavax reduces the incidence of shingles by almost 50%.
Shingrix is a V. zoster vaccine developed by GlaxoSmithKline which was approved in the United States by the FDA in October 2017. The Advisory Committee on Immunization Practices (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 4-year follow-up. Unlike Zostavax, which is given as a single shot, Shingrix is given as two intramuscular doses, two to six months apart.
A herpes-zoster subunit (HZ-su) vaccine has shown to be immunogenic and safe in adults with human immunodeficiency virus.
Chickenpox-like rashes were recognised and described by ancient civilizations; the relationship between zoster and chickenpox was not realized until 1888. It was in 1943 that Ruska noticed the similarity between virus particles isolated from the lesions of zoster and those from chickenpox.
In 1974 the first vaccine was introduced for chickenpox.
- "ICTV Taxonomy history: Human alphaherpesvirus 3" (html). International Committee on Taxonomy of Viruses (ICTV). Retrieved 9 January 2019.
- "ICTV 9th Report (2011) Herpesviridae" (html). International Committee on Taxonomy of Viruses (ICTV). Retrieved 9 January 2019.
Human herpesvirus 3 Human herpesvirus 3 [X04370=NC_001348] (HHV-3) (Varicella-zoster virus)
- "Pathogen Safety Data Sheets: Infectious Substances – Varicella-zoster virus". canada.ca. Pathogen Regulation Directorate, Public Health Agency of Canada. 2012-04-30. Retrieved 2017-10-10.
- Nagel, M. A.; Gilden, D. H. (July 2007). "The protean neurologic manifestations of varicella-zoster virus infection". Cleveland Clinic Journal of Medicine. 74 (7): 489–94, 496, 498–9 passim. doi:10.3949/ccjm.74.7.489. PMID 17682626.
- Steiner I; Kennedy PG; Pachner AR (2007). "The neurotropic herpes viruses: herpes simplex and varicella-zoster". Lancet Neurol. 6 (11): 1015–28. doi:10.1016/S1474-4422(07)70267-3. PMID 17945155.
- Tortora, gerard. Microbiology: An Introduction. Pearson. pp. 601–602.
- Becerra, Juan Carlos Lozano; Sieber, Robert; Martinetti, Gladys; Costa, Silvia Tschuor; Meylan, Pascal; Bernasconi, Enos (July 2013). "Infection of the central nervous system caused by varicella zoster virus reactivation: a retrospective case series study". International Journal of Infectious Diseases. 17 (7): e529–e534. doi:10.1016/j.ijid.2013.01.031. PMID 23566589.
- Nagel, M. A.; Cohrs, R. J.; Mahalingam, R; Wellish, M. C.; Forghani, B; Schiller, A; Safdieh, J. E.; Kamenkovich, E; Ostrow, L. W.; Levy, M; Greenberg, B; Russman, A. N.; Katzan, I; Gardner, C. J.; Häusler, M; Nau, R; Saraya, T; Wada, H; Goto, H; De Martino, M; Ueno, M; Brown, W. D.; Terborg, C; Gilden, D. H. (March 2008). "The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features". Neurology. 70 (11): 853–60. doi:10.1212/01.wnl.0000304747.38502.e8. PMC 2938740. PMID 18332343.
- Davison AJ, Scott JE (1986). "The complete DNA sequence of varicella-zoster virus". J Gen Virol. 67 (9): 1759–1816. doi:10.1099/0022-1317-67-9-1759. PMID 3018124.
- Chow, V. T.; Tipples, G. A.; Grose, C. (2012). "Bioinformatics of varicella-zoster virus: Single nucleotide polymorphisms define clades and attenuated vaccine genotypes". Infection, Genetics and Evolution. 18: 351–356. doi:10.1016/j.meegid.2012.11.008. PMC 3594394. PMID 23183312.
- Grose, C. (2012). "Pangaea and the Out-of-Africa Model of Varicella-Zoster Virus Evolution and Phylogeography". Journal of Virology. 86 (18): 9558–9565. doi:10.1128/JVI.00357-12. PMC 3446551. PMID 22761371.
- Loparev, V. N.; Rubtcova, E. N.; Bostik, V.; Tzaneva, V.; Sauerbrei, A.; Robo, A.; Sattler-Dornbacher, E.; Hanovcova, I.; Stepanova, V.; Splino, M.; Eremin, V.; Koskiniemi, M.; Vankova, O. E.; Schmid, D. S. (2009). "Distribution of varicella-zoster virus (VZV) wild-type genotypes in northern and southern Europe: Evidence for high conservation of circulating genotypes". Virology. 383 (2): 216–225. doi:10.1016/j.virol.2008.10.026. PMID 19019403.
- Zell, R.; Taudien, S.; Pfaff, F.; Wutzler, P.; Platzer, M.; Sauerbrei, A. (2011). "Sequencing of 21 Varicella-Zoster Virus Genomes Reveals Two Novel Genotypes and Evidence of Recombination". Journal of Virology. 86 (3): 1608–1622. doi:10.1128/JVI.06233-11. PMC 3264370. PMID 22130537.
- Loparev, V. N.; Rubtcova, E. N.; Bostik, V.; Govil, D.; Birch, C. J.; Druce, J. D.; Schmid, D. S.; Croxson, M. C. (2007). "Identification of Five Major and Two Minor Genotypes of Varicella-Zoster Virus Strains: A Practical Two-Amplicon Approach Used to Genotype Clinical Isolates in Australia and New Zealand". Journal of Virology. 81 (23): 12758–12765. doi:10.1128/JVI.01145-07. PMC 2169114. PMID 17898056.
- McGeoch DJ, Cook S (1994). "Molecular phylogeny of the alphaherpesvirinae subfamily and a proposed evolutionary timescale". J Mol Biol. 238 (1): 9–22. doi:10.1006/jmbi.1994.1264. PMID 8145260.
- Centers for Disease Control and Prevention (CDC) (March 2012). "FDA approval of an extended period for administering VariZIG for postexposure prophylaxis of varicella" (PDF). MMWR Morb. Mortal. Wkly. Rep. 61 (12): 212. PMID 22456121.
- Cornelissen, C. N. (2013). Lippincott's illustrated reviews: Microbiology (3rd ed.). Philadelphia: Lippincott Williams & Wilkins Health. pp. 255–272.
- "Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Centers for Disease Control and Prevention". MMWR Recomm Rep. 45 (RR–11): 1–36. July 1996. PMID 8668119.
- Marin M; Güris D; Chaves SS; Schmid S; Seward JF; Advisory Committee On Immunization Practices (June 2007). "Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep. 56 (RR–4): 1–40. PMID 17585291.
- Gagliardi, AM; Andriolo, BN; Torloni, MR; Soares, BG (3 March 2016). "Vaccines for preventing herpes zoster in older adults". The Cochrane Database of Systematic Reviews. 3: CD008858. doi:10.1002/14651858.CD008858.pub3. PMC 6516976. PMID 26937872.
- Gruber MF (20 October 2017). "Biologics License Application (BLA) for Zoster Vaccine Recombinant, Adjuvant" (PDF). Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration. Retrieved 16 November 2018.
- "ACIP: New Vaccine Recommendations for Shingles Prevention". MPR. October 25, 2017. Retrieved October 30, 2017.
- Berkowitz, Elchonon M.; Moyle, Graeme; Stellbrink, Hans-Jürgen; Schürmann, Dirk; Kegg, Stephen; Stoll, Matthias; Idrissi, Mohamed El; Oostvogels, Lidia; Heineman, Thomas C. (2015-04-15). "Safety and Immunogenicity of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in HIV-Infected Adults: A Phase 1/2a Randomized, Placebo-Controlled Study". Journal of Infectious Diseases. 211 (8): 1279–1287. doi:10.1093/infdis/jiu606. ISSN 0022-1899. PMC 4371767. PMID 25371534.
- Wood MJ. History of Varicella Zoster Virus.Herpes. 2000 Oct;7(3):60–65.
- Ruska H (1943). "Über das Virus der Varicellen und des Zoster". Klin Wochenschr. 22 (46–47): 703–704. doi:10.1007/bf01768631.
- Takahashi M, Otsuka T, Okuno Y, Asano Y, Yazaki T (1974). "Live vaccine used to prevent the spread of varicella in children in hospital". Lancet. 2 (7892): 1288–1290. doi:10.1016/s0140-6736(74)90144-5. PMID 4139526.