Human alphaherpesvirus 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, zoster virus, and Human herpesvirus 3 (HHV-3). VZV infections are species-specific to humans, but can survive in external environments for a few hours, maybe a day or two.[3]
Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein, referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. Latent, recurring infections are typical of this group of viruses, though the family name does not refer to latency. Herpesviridae can cause latent or lytic infections.
Chickenpox, also known as varicella, is a highly contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms small, itchy blisters, which eventually scab over. It usually starts on the chest, back, and face then spreads to the rest of the body. Other symptoms may include fever, tiredness, and headaches. Symptoms usually last five to seven days. Complications may occasionally include pneumonia, inflammation of the brain, and bacterial skin infections. The disease is often more severe in adults than in children. Symptoms begin 10 to 21 days after exposure to the virus.
A disease is a particular abnormal condition that negatively affects the structure or function of part or all of an organism, and that is not due to any external injury. Diseases are often construed as medical conditions that are associated with specific symptoms and signs. A disease may be caused by external factors such as pathogens or by internal dysfunctions. For example, internal dysfunctions of the immune system can produce a variety of different diseases, including various forms of immunodeficiency, hypersensitivity, allergies and autoimmune disorders.
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.[4]
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.[5] 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.[6]
Encephalitis is inflammation of the brain. Severity is variable. Symptoms may include headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.
Pneumonia is an inflammatory condition of the lung affecting primarily the small air sacs known as alveoli. Typically symptoms include some combination of productive or dry cough, chest pain, fever, and trouble breathing. Severity is variable.
Viral pneumonia is a pneumonia caused by a virus. Viruses are one of the two major causes of pneumonia, the other being bacteria; less common causes are fungi and parasites. Viruses are the most common cause of pneumonia in children, while in adults bacteria are a more common cause.
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.[7]
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,[8] 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.[6]
Postherpetic neuralgia (PHN) is neuropathic pain which occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus. Typically, the nerve pain (neuralgia) is confined to an area of skin innervated by a single sensory nerve, which is known as a dermatome. PHN is defined as dermatomal nerve pain that persists for more than 90 days after an outbreak of herpes zoster affecting the same dermatome. Several types of pain may occur with PHN including continuous burning pain, episodes of severe shooting or electric-like pain, and a heightened sensitivity to gentle touch which would not otherwise cause pain or to painful stimuli (hyperalgesia). Abnormal sensations and itching may also occur.
Mollaret's meningitis is a recurrent or chronic inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. Since Mollaret's meningitis is a recurrent, benign (non-cancerous), aseptic meningitis, it is also referred to as benign recurrent lymphocytic meningitis. It was named for Pierre Mollaret, the French neurologist who first described it in 1944.
VZV is closely related to the herpes 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 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 180–200nm in diameter. Their lipid envelope encloses the 100nm nucleocapsid of 162 hexameric and pentameric capsomeres arranged in an icosahedral form. Its DNA is a single, linear, double-stranded molecule, 125,000nt 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 8nm long.
Herpes simplex virus1 and 2, also known by their taxonomical names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are common and contagious. They can be spread when an infected person begins shedding the virus. About 67% of the world population under the age of 50 has HSV-1. In the United States more than one-in-six people have HSV-2. Although it can be transmitted through any intimate contact, it is one of the most common sexually transmitted infections.
Some viruses have viral envelopes covering their protective protein capsids. The envelopes are typically derived from portions of the host cell membranes, but include some viral glycoproteins. They may help viruses avoid the host immune system. Glycoproteins on the surface of the envelope serve to identify and bind to receptor sites on the host's membrane. The viral envelope then fuses with the host's membrane, allowing the capsid and viral genome to enter and infect the host.
Glycoproteins are proteins which contain oligosaccharide chains (glycans) covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.
Genomes
The genome was first sequenced in 1986.[9] 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.[10] 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.
Evolution
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.[11] 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).[12][13] 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.[12] 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.[14]
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.[15]
Treatment
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.[16] 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.[17]
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.[18] In 2007, the ACIP recommended a second dose of vaccine before school entry to ensure the maintenance of high levels of varicella immunity.[19]
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%.[20]
Shingrix is a V. zoster vaccine developed by GlaxoSmithKline which was approved in the United States by the FDA in October 2017.[21] 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.[22]
A herpes-zoster subunit (HZ-su) vaccine has shown to be immunogenic and safe in adults with human immunodeficiency virus.[23]
History
Chickenpox-like rashes were recognised and described by ancient civilizations; the relationship between zoster and chickenpox was not realized until 1888.[24] It was in 1943 that Ruska noticed the similarity between virus particles isolated from the lesions of zoster and those from chickenpox.[25]
In 1974 the first vaccine was introduced for chickenpox.[26]
Ramsay Hunt syndrome type 2, also known as herpes zoster oticus, is a disorder that is caused by the reactivation of varicella zoster virus in the geniculate ganglion, a nerve cell bundle of the facial nerve.
Shingles, also known as zoster or herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide stripe either on the left or right side of the body or face. Two to four days before the rash occurs there may be tingling or local pain in the area. Otherwise there are typically few symptoms though some may have fever, headache, or feel tired. The rash usually heals within two to four weeks; however, some people develop ongoing nerve pain which can last for months or years, a condition called postherpetic neuralgia (PHN). In those with poor immune function the rash may occur widely. If the rash involves the eye, vision loss may occur.
Herpes virus may refer to:
Aciclovir (ACV), also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following transplant and severe complications of Epstein-Barr virus infection. It can be taken by mouth, applied as a cream, or injected.
Valaciclovir, also spelled valacyclovir, is an antiviral medication used to treat outbreaks of herpes simplex or herpes zoster (shingles). It is also used to prevent cytomegalovirus following a kidney transplant in high risk cases. It is taken by mouth.
Virus latency is the ability of a pathogenic virus to lie dormant (latent) within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection. Latency is the phase in certain viruses' life cycles in which, after initial infection, proliferation of virus particles ceases. However, the viral genome is not fully eradicated. The result of this is that the virus can reactivate and begin producing large amounts of viral progeny without the host becoming reinfected by new outside virus, and stays within the host indefinitely.
Brivudine is an antiviral drug used in the treatment of herpes zoster ("shingles"). Like other antivirals, it acts by inhibiting replication of the target virus.
Human Herpes Virus (HHV) Infected Cell Polypeptide 0 (ICP0) is a protein, encoded by the DNA of herpes viruses. It is produced by herpes viruses during the earliest stage of infection, when the virus has recently entered the host cell; this stage is known as the immediate-early or α ("alpha") phase of viral gene expression. During these early stages of infection, ICP0 protein is synthesized and transported to the nucleus of the infected host cell. Here, ICP0 promotes transcription from viral genes, disrupts structures in the nucleus known as nuclear dots or promyelocytic leukemia (PML) nuclear bodies, and alters the expression of host and viral genes in combination with a neuron specific protein. At later stages of cellular infection, ICP0 relocates to the cell cytoplasm to be incorporated into new virion particles.
Zoster vaccines are two vaccines that have been shown to reduce the rates of herpes zoster. One type, Zostavax, is essentially a larger-than-normal dose of the chickenpox vaccine, as both shingles and chickenpox are caused by the same virus, the varicella zoster virus (VZV). A recombinant version, Shingrix, was approved in the United States in 2017.
Varicella vaccine, also known as chickenpox vaccine, is a vaccine that protects against chickenpox. One dose of vaccine prevents 95% of moderate disease and 100% of severe disease. Two doses of vaccine are more effective than one. If given to those who are not immune within five days of exposure to chickenpox it prevents most cases of disease. Vaccinating a large portion of the population also protects those who are not vaccinated. It is given by injection just under the skin.
VZV globulin or VZV antibodies is an immune system medication that is used mostly for immunosuppressed patients who have been or may be exposed to the varicella zoster virus. It shortens the course of cutaneous disease and may protect against its dissemination. Varicella zoster virus is a human herpes virus that causes chickenpox, shingles, Ramsay Hunt syndrome type II, and postherpetic neuralgia. Unlike a Zoster vaccine which provides durable immunity, the protection is passive and short term; it may need to be readministered every 2-4 weeks as necessary. This medication is not recommended for administration to immune-competent persons for treatment of active disease.
Varicella may refer to:
Herpes simplex research includes all medical research that attempts to prevent, treat, or cure herpes, as well as fundamental research about the nature of herpes. Examples of particular herpes research include drug development, vaccines and genome editing. HSV-1 and HSV-2 are commonly thought of as oral and genital herpes respectively, but other members in the herpes family include chickenpox, cytomegalovirus (CMV), and Epstein-Barr (EBV). There are many more members that infect animals other than humans, some of which cause disease in companion animals or have economic impacts in the agriculture industry.
Stephen E. Straus was an American physician, immunologist, virologist and science administrator. He is particularly known for his research into human herpesviruses and chronic fatigue syndrome, and for his discovery of the autoimmune lymphoproliferative syndrome genetic disorder. He headed the Laboratory of Clinical Investigation of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), and served as the founding director of the NIH's National Center for Complementary and Alternative Medicine.
↑ "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)
↑ 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. PMID17682626.
↑ 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. PMID17945155.
1 2 Tortora, gerard. Microbiology: An Introduction. Pearson. pp.601–602.
1 2 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. PMID19019403.
↑ 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. PMID8145260.
↑ 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. PMID4139526.
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