Parvovirus B19
Primate erythroparvovirus 1 | |
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Electron micrograph of Parvoviruses in blood | |
Virus classification![]() | |
(unranked): | Virus |
Realm: | Monodnaviria |
Kingdom: | Shotokuvirae |
Phylum: | Cossaviricota |
Class: | Quintoviricetes |
Order: | Piccovirales |
Family: | Parvoviridae |
Genus: | Erythroparvovirus |
Species: | Primate erythroparvovirus 1
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Synonyms | |
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Human parvovirus B19,generally referred to asB19 virus(B19V),parvovirus B19[1]or sometimeserythrovirus B19,[2]is a known human virus in thefamilyParvoviridae,genusErythroparvovirus;it measures only 23–26nmin diameter.[3]Human parvovirus b19is a below-species classification ofErythroparvovirus primate1.[4]The name is derived from Latinparvum,meaning small, reflecting the fact that B19 ranks among the smallestDNA viruses.B19 virus is most known for causing disease in the pediatric population; however, it can also affect adults. It is the classic cause of the childhoodrashcalledfifth diseaseor erythema infectiosum, or "slapped face syndrome".[5][6]The name comes from it being the fifth in a list of historical classifications of common skin rash illnesses in children.[7]
The virus was discovered by chance in 1975 byAustralianvirologistYvonne Cossart.[3][6]The name B19 originated from the coding of a serum sample, number 19 in panel B.[6][8]
Virology
[edit]Erythroviruses belong to theParvoviridaefamily of small DNA viruses.[9]Human parvovirus B19 is a non-enveloped,icosahedralvirus that contains asingle-strandedlinear DNAgenomeof approximately 5,600base pairsin length.[10]B19V's nonenveloped viral particles are ~22 to 24 nm in diameter which are quite small compared to other parvoviruses.[3]The infectious particles may contain either positive or negative strands of DNA. Theicosahedral capsidconsists of 60 capsomeres, consisting of twostructural proteins,VP1 (83kDa) and VP2 (58 kDa), which are identical except for 227amino acidsat the amino-terminal of the VP1-protein, the so-called VP1-unique region. VP2 is the majorcapsid protein,and comprises approximately 95% of the total virus particle. VP1-proteins are incorporated into the capsid structure in a non-stoichiometricalrelation (based onantibody-binding analysis andX-ray structural analysisthe VP1-unique (VP1u) region is assumed to be exposed at the surface of the virus particle.[11]VP1u is located in the N-terminus of the VP1.[12]At each end of the DNA molecule there are palindromic sequences which form "hairpin" loops. The hairpin at the3' endserves as a primer for the DNA polymerase.[13]It is classified as an erythrovirus because of its capability to invadered blood cellprecursors in thebone marrow.Threegenotypes(with subtypes) have been recognised.[14]
The genome of human parvovirus B19 encodes four other proteins in addition to VP1 and VP2 and also some smaller proteins whose function is still unknown.[15]The most notable of these is the large nonstructural protein commonly referred to as NS1. NS1 is a multifunctional protein that has a role in binding and operating on the p6 promoter which gives NS1 the ability to control the transcription of the B19V genome.[16]NS1 sequence-specifically binds and cleaves DNA via restriction endonuclease activity at its N-terminus.[17]NS1 is responsible for the regulation of certain cellular promoters including the p21/WAF1 promoter,[18]and is thought to regulate the virus' own promoter.[19]The 11 kDa protein encoded by the viral genome has been implicated in viral DNA replication.[20]
The nucleotide substitution rate for total coding DNA has been estimated to be 1.03 (0.6-1.27) x 10−4substitutions/site/year.[21]This rate is similar to that of other single-stranded DNA viruses. VP2 codons were found to be underpurifying selection.In contrast VP1 codons in the unique part of the gene were found to be underdiversifying selection.This diversifying selection is consistent with persistent infection as this part of the VP1 protein contains epitopes recognised by the immune system.[citation needed]
Like other nonenveloped DNA viruses,pathogenicityof parvovirus B19 involves binding to host cell receptors, internalization, translocation of the genome to the host nucleus, DNA replication, RNA transcription, assembly of capsids and packaging of the genome, and finallycell lysiswith release of the mature virions.[22]In humans theP antigen(also known as globoside) is the cellular receptor for parvovirus B19 virus that causes erythema infectiosum (fifth disease) in children. This infection is sometimes complicated by severe aplastic anemia caused by lysis of early erythroid precursors.[citation needed]
Evolution
[edit]Themost recent common ancestorof the extant strains has been dated to about 12,600 years ago.[23]Three genotypes—1, 2 and 3—are recognised. A recombination between types 1 and 3 gave rise to genotype 2 between 5,000 and 6,800 years ago.[citation needed]
Transmission
[edit]The virus is primarily spread by infectedrespiratorydroplets; however, blood-borne transmission has also been reported.[24]As with all respiratory pathogens once presumed to transmit via respiratory droplets, it is highly likely to be carried by the aerosols generated during routine breathing, talking, and even singing.[25]The secondary attack risk for exposed household persons is about 50%, and about half of that for classroom contacts.[6][26]Transmission can happen from a mother that has B19V infection during pregnancy. The baby can get infected by bloodstream and therefore develop a severe anemia.[27]
Infectivity and symptoms
[edit]Two out of ten infected people do not experience any symptoms but are still highly infective. The B19V infection starts with flu-like symptoms consisting fever, headache, runny nose, sore throat, joint pain and rash.[28]Symptoms begin some six days after exposure (between 4 and 28 days, with the average being 16 to 17 days[29]) and last about a week. The rash that children experience will appear after few days after the initial symptoms and can spread all over the body.[28]
Infected patients with normal immune systems are contagious before becoming symptomatic, but probably not after.[30]Individuals with B19IgG antibodiesare generally considered immune to recurrent infection, but reinfection is possible in a minority of cases.[31]About half of adults are B19-immune due to a past infection.[27]
Immunocompromised patients (organ transplant, HIV etc.) are prone to complications that affect the nerves, joints or bloodstream.[28]
Epidemiology
[edit]A significant increase in the number of cases is seen every three to four years; the lastepidemicyear was 1998.[32]Outbreaks can arise especially in nurseries and schools.
Parvovirus B19 causes an infection in humans only. Cat and dog parvoviruses do not infect humans due to animals having their own parvoviruses. There is always a possibility for a spillover. There is no vaccine available for human parvovirus B19,[33]though attempts have been made to develop one.[34][35]
Role in disease
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/b/ba/Fifth_disease.jpg/220px-Fifth_disease.jpg)
![](https://upload.wikimedia.org/wikipedia/commons/thumb/4/4d/14_month_old_with_Fifth_Disease.jpg/220px-14_month_old_with_Fifth_Disease.jpg)
Fifth disease
[edit]Fifth diseaseorerythema infectiosumis only one of several expressions of parvovirus B19. The associated bright red rash of the cheeks gives it the nickname "slapped cheek syndrome".[6]Any age may be affected, although it is most common in children aged six to ten years. It is so named because it was the fifth most common cause of a pink-red infection associated rash to be described by physicians (many of the others, such asmeaslesandrubella,are rare now).[36]
Once infected, patients usually develop the illness after anincubation periodof four to fourteen days. The disease commences with high fever and malaise, when the virus is most abundant in the bloodstream, and patients are usually no longer infectious once the characteristic rash of this disease has appeared.[33]The following symptoms are characteristic:
- A usual brief viralprodromewith fever, headache, nausea, diarrhea.
- As the fever breaks, a red rash forms on the cheeks, with relative pallor around the mouth ( "slapped cheek rash" ), sparing the nasolabial folds, forehead, and mouth.
- "Lace-like, (reticular)" red rash on trunk or extremities then follows the facial rash. Infection in adults usually only involves the reticular rash, with multiple joint pain predominating.
- Exacerbation of rash by sunlight, heat, stress.
Papular purpuric gloves and socks syndrome
[edit]Teenagers or young adults may develop the so-calledPapular purpuric gloves and socks syndrome.It is acutaneouscondition characterized bypruritus,edema,anderythemaof the hands and feet.[37]: 401 In 1996, an association with parvovirus B19 was described, after virus was demonstrated in skin biopsy samples,[38]subsequently corroborated in numerous publications.[39] [40]
Polyarthropathy syndrome
[edit]Arthralgiasandarthritisare commonly reported in association with parvovirus B19 infection in adults in the absence of skin findings, whereas erythema infectiosum is the main symptom observed in children. The occurrence of arthralgia coincides with the initial detection of circulating IgM- and IgG-antibodies against the viral structural proteins VP1 and VP2. Parvovirus B19 infection may affect the development of arthritis.[11]In adults (and perhaps some children), parvovirus B19 can lead to aseronegative arthritiswhich is usually easily controlled withanalgesics.[41]Women are approximately twice as likely as men to experience arthritis after parvovirus infection. Possibly up to 15% of all new cases of arthritis are due to parvovirus, and a history of recent contact with a patient and positiveserologygenerally confirms the diagnosis.[30]This arthritis does not progress to other forms of arthritis. Typically joint symptoms last 1–3 weeks, but in 10–20% of those affected, it may last weeks to months.[6][33]
A Danish study has links between B19 with polymyalgia rheumatica.[42]
Aplastic crisis and chronic erythroid hypoplasia
[edit]Although most patients have a decrease oferythropoiesis(production ofred blood cells) during parvovirus infection, it is most dangerous in patients with pre-existing bone marrow stress, for examplesickle cell anemiaorhereditary spherocytosis,[43][44]and are therefore heavily dependent on erythropoiesis due to the reduced lifespan of the red cells. This is termed "aplastic crisis" (also calledreticulocytopenia). It is treated withblood transfusion.
Parvovirus B19 is a cause of chronic anemia in individuals with immunodeficiency, receiving immunosuppressive therapy or withHIVinfection. Treatment with intravenous immunoglobulin usually resolves the anemia although relapse can occur. Parvovirus infection may trigger an inflammatory reaction in AIDS patients who have just begun antiretroviral therapy.[45]
Hydrops fetalis
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/5/57/Parvovirus_infection_-_cropped_2_-_very_high_mag.jpg/220px-Parvovirus_infection_-_cropped_2_-_very_high_mag.jpg)
Parvovirus infection in pregnant women is associated withhydrops fetalisdue to severe fetalanemia,sometimes leading tomiscarriageorstillbirth.[33][46]This is due to a combination ofhemolysisof the red blood cells, as well as the virus directly negatively affecting the red blood cell precursors in the bone marrow. The risk of fetal loss is about 10% if infection occurs before pregnancy week 20 (especially between weeks 14 and 20), but minimal after then. Routine screening of the antenatal sample would enable the pregnant mother to determine the risk of infection.[citation needed]Knowledge of her status would allow the mother to avoid contact with individuals suspected or known to have an ongoing infection, however, at the present time, antenatal testing for immunity is not recommended, since there is no good means to prevent the infection, there is no specific therapy and there are no vaccines available. It may increase maternal anxiety and fear without proven benefit. The best approach would be to recommend all pregnant women to avoid contact with children with current symptoms of infection, as described above. The risk to the fetus will be reduced with correct diagnosis of the anemia (byultrasoundscans) and treatment (byblood transfusions). There is some evidence that intrauterine parvovirus B19 infection leads to developmental abnormalities in childhood.[47]
Treatment
[edit]At the moment, there are no treatments that directly target parvovirus B19 virus.[48]Intravenous immunoglobulin therapy(IVIG) therapy has been a popular alternative because doctors can administer it without stopping chemotherapy drugs like MEL-ASCT.[49]Also, the treatment's side effects are rare as only 4 out of 133 patients had complications (2 hadacute kidney injuryand 2 had pulmonary edema) even though 69 of the patients had organ transplants and 39 of them were HIV positive.[50]This is a large improvement over administeringrituximab.[citation needed]The monoclonal antibody against the CD20 protein has been shown to cause acute hepatitis,[51]neutropenia via parvovirus B19 reactivations,[52]and even persistent parvovirus B19 infection.[53]However, it is important to note that IVIG therapy is not perfect as 34% of treated patients will have a relapse after 4 months.[50]
Diagnostics and Vaccination
[edit]There is no routine laboratory test for B19V, but in case of the doctor is suspecting a B19V infection patient's blood will be drawn. The blood is then tested for antibodies.[27]
As of 2020, no approved human vaccine existed against parvovirus B19.[54]Bernstein et. al.[35]tested in 2011 a possible candidate vaccine that was produced in insect cells. For the vaccine VP2/VP1 VLPs (virus-like particle) were used. This vaccine was approved to the I clinical phase, but was stopped due to unexplained reactions in patients. It was argued that the reaction could have been due to the PLA2 activity in VP1u. The reaction was either to the PLA2 activity releasing arachidonic acid and precursors of inflammatory mediators or the usage of insect cells. The PLA2 activity can be reduced or fully removed with site-directed mutagenesis. So this could still act as a candidate vaccine, but further research is needed.[12]
See also
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