Induction of an invasive phenotype by human parvovirus B19 in normal humansynovial fibroblasts

Objective. To investigate the possible role of human parvovirus B19 as an e tiologic agent in rheumatoid arthritis (RA), with particular emphasis on it s ability, to induce invasiveness in human synovial fibroblasts. Methods. We established an experimental in vitro system in which normal pri mary human synovial fibroblasts were treated with or without parvovirus B19 -containing human sera for 7 days. The fibroblasts were then tested for the ir ability to degrade reconstituted cartilage matrix using a well-character ized cartilage invasion assay system. Results. Incubation with parvovirus B19-containing serum induced an invasiv e phenotype in normal human synovial fibroblasts. B19 serum-treated synovia l fibroblasts exhibited an increase in invasion of up to 248% compared with the activity of fibroblasts in media alone, in contrast to B19-negative se ra-treated synovial fibroblasts, which exhibited no significant change comp ared with that in media alone. In addition, preincubation of viremic serum with a neutralizing antibody to B19 abrogated the observed effect. Conclusion. These results provide direct evidence regarding the ability of parvovirus B19 to induce invasive properties in normal human synovial fibro blasts. Parvovirus B19 has been proposed as an etiologic agent of RA, and o ur data provide the first biologic link between exposure to B19 and phenoty pic changes in normal human synovial fibroblasts.