Host range restriction of parainfluenza virus growth occurs at the level of virus genome replication.

To illuminate the molecular basis for host range restriction of parainfluenza virus replication, we have examined the types of virus macromolecules produced during abortive infection of nonpermissive MDBK cells with human parainfluenza virus type 1 (hPIV1). While these cells do not support production of hPIV1 virus, they can be infected by hPIV1 as evidenced by accumulation of intracellular viral NP and HN proteins. HPIV1 is also able to drive transcription of a synthetic analog of Sendai virus (SV) genome RNA transfected into virus-infected MDBK cells. In contrast to transcription, hPIV1 genome replication does not occur in MDBK cells. Intracellular full-length genome RNA was detected only in trace amounts 2 days after infection, and was undetectable 4 days after infection. Full-length antigenome (+) sense RNA was not detectable. Nucleocapsid complexes failed to accumulate in the cytoplasm of nonpermissive cells, and no detectable nucleocapsids were released into the medium as virus particles. The data indicate that defective vRNA synthesis and/or nucleocapsid formation is responsible for the inability of hPIV1 to grow in MDBK cells. Our data also show that hPIV1 is capable of providing all helper functions for packaging SV synthetic genome analogs into infectious particles, but these SV-specific RNAs encapsidated with hPIV1 proteins are in turn not replicated by SV proteins. These results suggest that functional protein-protein interactions between parainfluenza virus strains have more stringent requirements than do protein-RNA interactions.