摘要：

Human parvovirus B19, discovered in 1975[1] and first linked with human disease in 1981,[2] is a small single stranded DNA virus classified within the family Parvoviridae, and the genus Erythrovirus, having tropism primarily for erythroid precursors. B19 is the only parvovirus which has been clearly linked with disease in humans. It replicates only in human cells and is autonomous, not requiring the presence of a helper virus. Acute B19 virus infection is classically associated with the childhood rash illness, erythema infectiosum (EI), arthralgia, fetal death, and transient aplastic crisis (TAC) in those with shortened red cell survival. However, it has been assumed that in those with a normal immune system, the virus has a relatively simple pathogenesis and that after the acute phase the virus is cleared by a specific humoral immune response. However, increasingly B19 virus and B19 infection have been reported in association with quite atypical and unpredictable findings based on previous assumptions. For example, persistence of the virus in various tissues after acute infection in apparently normal subjects and the association of B19 infection with various connective tissue and autoimmune diseases. This paper will therefore summarise present knowledge of the virus, its known and potential pathogenetic mechanisms, and its associations with human disease, with an emphasis on rheumatic disease. Virology The B19 genome consists of a single stranded linear molecule of 5596 nucleotides, which is composed of an internal coding sequence of 4830 nucleotides flanked by terminal repeat sequences of 383 nucleotides each.[3] These terminal repeat sequences are imperfect palindromes and fold back on themselves to form hairpin loops.[4] Viral replication is thus self primed by the 3' terminus,[5] and in minute virus of mice, a related parvovirus, has recently been shown to require the host cell transcriptional modulator, parvovirus initiation factor.[6] This is a site-specific DNA-binding complex consisting of p96 and p79 subunits, which have 40% amino acid identity focused particularly within a 94 residue region containing the sequence KDWK, and may modulate transcription of many genes. The P6 promoter at the far left side of the genome initiates transcription of all B19 proteins.[7] The non-structural protein, NS1, is encoded by the left side of the genome (nucleotides 435-2448) and is approximately 77 kDa.[8] Parvovirus non-structural proteins are fairly homologous between species, consistent with their role in virus propagation, and B19 NS1 contains two phosphorylation sites, an amidation site and a nucleotide binding site.[9] NS1 is localised to the nucleus of infected cells,[8] is found covalently bound to mature virions,[10] and may nick its replicative DNA intermediates to facilitate viral packaging.[5] NS1 is cytotoxic to various host cells[11] possibly owing to host DNA nickase activity, which is abrogated by mutations within the nucleoside triphosphate-binding domain.[12] B19 NS1 has also been shown to upregulate human interleukin 6 (IL6) gene expression[13] and to induce apoptosis in cells of the erythroid lineage.[14] Structural proteins, VP1 and VP2, are encoded in the same open reading frame by nucleotides 2444-4786 and 3125-4786 with production of proteins of 84 and 58 kDa,...

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