Differential ability of wild-type and vaccine strains of rubella virus to replicate and persist in human joint tissue.

Natural rubella has been reported to be associated with a higher incidence of arthropathy than immunisation with rubella vaccine. In addition, the different vaccines (HPV77/DE5, RA27/3, Cendehill) have been shown to vary in their association with joint symptoms in clinical trials. To investigate possible reasons for these differences in arthritogenicity, the susceptibility of human joint tissue to five rubella virus strains (three vaccines and two wt+) has been examined. Human joint tissue in either organ or dispersed cell-culture was infected in vitro and the degree of replication and persistence of each rubella strain compared. The wt+ strains (M33 and Therien) replicated to high titre in both cell and organ cultures and persisted for over 2 months. The HPV77/DE5 strain (Meruvax I) showed a very similar pattern. In contrast, the replication of RA27/3 (Meruvax II) and Cendehill (Cendevax) was highly restricted in joint cells and both of these strains showed very limited ability to penetrate and persist in the organ cultures. These results concur with the differences in arthritogenicity observed between the strains in vivo, suggesting that local viral replication may play a role in the pathogenesis of rubella-associated arthritis.