Utilization of Homotypic and Heterotypic Proteins of Vesicular Stomatitis Virus by Defective Interfering Particle Genomes for RNA Replication and Virion Assembly: Implications for the Mechanism of Homologous Viral Interference

Abstract

ABSTRACT Defective interfering (DI) particles of Indiana serotype of vesicular stomatitis virus (VSV Ind ) are capable of interfering with the replication of both homotypic VSV Ind and heterotypic New Jersey serotype (VSV NJ ) standard virus. In contrast, DI particles from VSV NJ do not interfere with the replication of VSV Ind standard virus but do interfere with VSV NJ replication. The differences in the interfering activities of VSV Ind DI particles and VSV NJ DI particles against heterotypic standard virus were investigated. We examined the utilization of homotypic and heterotypic VSV proteins by DI particle genomic RNAs for replication and maturation into infectious DI particles. Here we show that the RNA-nucleocapsid protein (N) complex of one serotype does not utilize the polymerase complex (P and L) of the other serotype for RNA synthesis, while DI particle genomic RNAs of both serotypes can utilize the N, P, and L proteins of either serotype without serotypic restriction but with differing efficiencies as long as all three proteins are derived from the same serotype. The genomic RNAs of VSV Ind DI particles assembled and matured into DI particles by using either homotypic or heterotypic viral proteins. In contrast, VSV NJ DI particles could assemble only with homotypic VSV NJ viral proteins, although the genomic RNAs of VSV NJ DI particles could be replicated by using heterotypic VSV Ind N, P, and L proteins. Thus, we concluded that both efficient RNA replication and assembly of DI particles are required for the heterotypic interference by VSV DI particles.