Integrity and full coding sequence of B19 virus DNA persisting in human synovial tissue

Abstract

Primary infection by human parvovirus B19 is often accompanied by arthropathy of varying duration, of which the most severe cases can be indistinguishable from rheumatoid arthritis (RA). While this might seem to imply a role in RA pathogenesis, recent studies have verified long-term persistence of B19 DNA in synovial tissue not only in patients with rheumatoid or juvenile arthritis, but also in immunocompetent, non-arthritic individuals with a history of prior B19 infection. However, the latter data are based on PCR amplification of short segments of DNA, with little sequence information. We determined the nucleotide sequence and examined the integrity of the protein-coding regions of B19 genomes persisting in synovial tissue and compared the results with data from synovial tissues of recently infected patients. In synovium of both previously and recently infected subjects, the viral coding regions were found to be present in an apparently continuous, intact DNA molecule. Comparison with sequences reported from blood or bone marrow showed that the synoviotropism or persistence of the B19 virus DNA was not due to exceptional mutations or particular genotype variants. The synovial retention of full-length viral genomes may represent a physiological process functioning in long-term storage of foreign macromolecules in this tissue.

Genetic Diversity within Human Erythroviruses: Identification of Three Genotypes

“…Partial sequence data from different coding regions of the viral genome have confirmed this high degree of similarity with a larger number of isolates (12,15,23,25,48). For instance, sequence variation of the VP1/VP2 gene has been reported to be very low among B19 virus isolates obtained from a single community-wide outbreak (0 to 0.6% base substitutions) and only slightly greater among B19 virus isolates obtained from distinct epidemiological settings and geographical area, ranging between 0.5 and 4.8% for the most distant isolates (12).…”

“…The genetic diversity among B19 virus isolates has been reported to be very low, with less than 1 to 2% nucleotide divergence in the whole genome, although full-length sequences are available only for a limited number of isolates (24,25,31,42). Partial sequence data from different coding regions of the viral genome have confirmed this high degree of similarity with a larger number of isolates (12,15,23,25,48).…”

Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood

“…However, this finding also indicates that parvovirus B19 infection is more frequently associated with rheumatic disease in childhood than in adults. Since viral DNA has been shown to persist in the synovial tissue after clearance from the peripheral blood and/or synovial fluid (7,(39)(40)(41)(42), it has to be assumed that virus reactivation may occur in the synovial tissue sporadically or in association with inflammatory processes due to rheumatic disease and/or other infectious agents such as borrelia or streptococci. Similar interactions between inflammation, cell differentiation, and reactivation of latent or persistent virus are well known from studies with herpes and papillomavirus systems.…”

Bioportfolio: Lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue

“…At the global and epidemiological level, it provides a database for analysis of the occurrence and circulation of viruses and their variants. Moreover, in light of the well preserved integrity and full-length coding potential of the persistent macromolecular viral DNA genomes (27), the Bioportfolio might provide the desired long-term permanence for gene therapy vectors, which, in the future, could be designed in accordance with this innate characteristic of the human body.…”

“…Serodiagnostics (i.e., IgG seropositivity; IgG avidity, IgG epitope type specificity, and the absence of IgM ruling out recent primary infection) verified the specificity of the original findings and showed the DNA persistence in synovium to be long (24,27). Besides revolutionizing the diagnostic criteria of parvovirus arthropathy (28,29), the tissue persistence has evoked wide interest in the possible etiopathogenic role of these viruses in inflammatory and other chronic diseases (30)(31)(32)(33)(34)(35)(36).…”