Interference by a non-defective variant of influenza A virus is due to enhanced RNA synthesis and assembly.
Mouse-adapted influenza A virus, FM-MA, interferes with the replication of wild-type strains on co-infection. The interference phenotype was previously mapped to FM-MA segment 2 encoding a mutant PB1 protein, the catalytic component of the RNA polymerase complex. To identify the point at which FM-MA interferes with wild-type A/HK/1/68 (HK), the relative levels of transcription and genome replication of the PB1, NP and M1 genes were determined for FM-MA and HK viruses in co-infected cells using RT-PCR. All stages of HK macromolecular synthesis (primary and secondary transcription, genomic RNA, complementary RNA and protein synthesis) were suppressed relative to FM-MA. Infection with HK virus alone resulted in the accumulation of similar or greater amounts of RNA at late times post-infection relative to FM-MA thus indicating that the presence of FM-MA specifically compromised HK transcription and replication in co-infected cells. However early in infection FM-MA was ten times more active in mRNA transcription than HK or its parental strain FM. FM-MA's ability to interfere was primarily due to an increased capacity for primary transcription. FM-MA genomes were also selectively assembled into progeny virus from cells co-infected with HK and FM-MA, a step which was distinct from the capacity for enhanced RNA synthesis. This suggests that interference of HK growth by FM-MA in mixed infections results from two distinct events: a preferential synthesis of FM-MA-specific macromolecules which is then augmented by a preferential assembly of FM-MA genomes.
Bailly
J E
JE
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ont., Canada.
Brown
E G
EG
D000818:Animals; D002460:Cell Line; D004285:Dogs; D014644:Genetic Variation; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D018075:RNA, Complementary; D012333:RNA, Messenger; D012367:RNA, Viral / Q000096:biosynthesis*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014158:Transcription, Genetic; D014762:Viral Interference; D014764:Viral Proteins / Q000096:biosynthesis; D019065:Virus Assembly
D018075:RNA, Complementary; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; D012194:RNA-Directed DNA Polymerase