Persistent infection with human parainfluenza virus 3 in CV-1 cells: analysis of the role of defective interfering particles.

Persistent infection of cultured cells with human parainfluenza virus type 3 (HPF3), established following infection at high multiplicity, has been associated with the presence of one or more viral defective-interfering (DI) particles in addition to standard viral genomes. We recently showed that persistent infection can also be established after low multiplicity infection, a condition not generally associated with amplification of DI particles. The association of DI particle genomes with persistent infection was therefore studied after infection with low multiplicity. Persistently infected cell cultures were established after low multiplicity infection with HPF3 in the presence of exogenous bacterial neuraminidase, and viral nucleocapsid RNA was analyzed for the presence of DI genomes at each passage after infection. In addition, the timing of DI particle appearance was assessed after infection with high multiplicity, a condition known to favor the amplification of DI particles. DI particles genomes did not appear until at least seven passages of persistently infected cell cultures, after either low or high multiplicity infection. Our data suggest that DI particles are not required for establishment of persistent infection of CV-1 cells by HPF3 and that DI particles are not generated early in infection. Despite reports of the association of paramyxovirus DI particles with persistent infection in culture, the role of these particles in HPF3 persistence is unknown; our findings offer insight into the complex interplay of viral and host factors in persistent infection.