Parvovirus B19 (also called B19 virus (B19V), Human parvovirus B19, or sometimes erythrovirus B19) is a human virus most known for causing disease in children, though it can also affect adults. It is the classic cause of the childhood rash called fifth disease or erythema infectiosum. The virus's name is derived from Latin parvum, meaning 'small', as B19 ranks among the smallest DNA viruses, measuring only 23–26 nm in diameter. The virus was discovered by chance in 1975 by Australian virologist Yvonne Cossart. The name B19 originated from the coding of a serum sample, number 19 in panel B.
Virology Erythroviruses belong to the Parvoviridae family of small DNA viruses. It is in the genus Erythroparvovirus and assigned to the species Erythroparvovirus primate1. Human parvovirus B19 is a non-enveloped, icosahedral virus that contains a single-stranded linear DNA genome of approximately 5,600 base pairs in length. B19V's nonenveloped viral particles are ~22 to 24 nm in diameter which are quite small compared to other parvoviruses. The infectious particles may contain either positive or negative strands of DNA. The icosahedral capsid consists of 60 capsomeres, consisting of two structural proteins, VP1 (83 kDa) and VP2 (58 kDa), which are identical except for 227 amino acids at the amino-terminal of the VP1-protein, the so-called VP1-unique region. VP2 is the major capsid protein, and comprises approximately 95% of the total virus particle. VP1-proteins are incorporated into the capsid structure in a non-stoichiometrical relation (based on antibody-binding analysis and X-ray structural analysis the VP1-unique (VP1u) region is assumed to be exposed at the surface of the virus particle. VP1u is located in the N-terminus of the VP1. At each end of the DNA molecule there are palindromic sequences which form "hairpin" loops. The hairpin at the 3' end serves as a primer for the DNA polymerase. It is classified as an erythrovirus because of its capability to invade red blood cell precursors in the bone marrow. Three genotypes (with subtypes) have been recognised. 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. 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. NS1 binds and cleaves DNA in a sequence specific manner via restriction endonuclease activity of an N-terminal domain. Only single stranded DNA is cleaved, but double stranded DNA is preferentially bound, with high cooperativity that facilitates the binding of multiple NS1 units. NS1 is responsible for the regulation of certain cellular promoters including the p21/WAF1 promoter, and is thought to regulate the virus' own promoter. The 11 kDa protein encoded by the viral genome has been implicated in viral DNA replication. The nucleotide substitution rate for total coding DNA has been estimated to be 1.03 (0.6-1.27) × 10−4 substitutions/site/year. This rate is similar to that of other single-stranded DNA viruses. VP2 codons were found to be under purifying selection. In contrast VP1 codons in the unique part of the gene were found to be under diversifying selection. This diversifying selection is consistent with persistent infection as this part of the VP1 protein contains epitopes recognised by the immune system. Like other nonenveloped DNA viruses, pathogenicity of 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 finally cell lysis with release of the mature virions. In humans the P 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. Studies of Parvovirus B19 (B19V) have provided insights into its persistence and integration within human tissues. Analyses revealed that B19V primarily resides in endothelial cells, monocytes, and B cells, with few documented integration events in vivo. Although B19V DNA integration has been observed in vitro, its low prevalence in sampled tissues suggests that alternative mechanisms may contribute to lifelong persistence. In one case involving pulmonary carcinoma, a B19V integration junction was found in the colon, indicating possible interactions with host genomic elements.
Evolution The most recent common ancestor of the extant strains has been dated to about 12,600 years ago. 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.
Transmission The virus is primarily spread by infected respiratory droplets; however, blood-borne transmission has also been reported. The secondary attack risk for exposed household persons is about 50%, and about half of that for classroom contacts. 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.
Infectivity and symptoms 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 of fever, headache, runny nose, sore throat, joint pain and rash. Symptoms begin some six days after exposure (between 4 and 28 days, with the average being 16 to 17 days) 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. Infected patients with normal immune systems are contagious before becoming symptomatic, but probably not after. Individuals with B19 IgG antibodies are generally considered immune to recurrent infection, but reinfection is possible in a minority of cases. About half of adults are B19-immune due to a past infection. Immunocompromised patients (organ transplant, HIV etc.) are prone to complications that affect the nerves, joints or bloodstream.
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