Inhibitory effects of vesicular stomatitis virus on cellular and influenza viral RNA metabolism and protein synthesis.
Infection with vesicular stomatitis virus (VSV) results in the rapid inhibition of cellular macromolecular synthesis, including transcription, translation, and maturation of the U1 and U2 snRNPs. Unlike infection with VSV, influenza virus infection did not result in the inhibition of either the processing of U1 and U2 snRNAs or the assembly of the RNPs. Although influenza virus relies on the cellular splicing apparatus to generate viral mRNAs, the maturation of snRNPs was inhibited during double infections with VSV. However, this inhibition of snRNP maturation had no effect on the splicing of a cellular pre mRNA in extracts prepared from VSV-infected HeLa cells. Thus, the effects of VSV on the processing and assembly of snRNPs appear to involve virus-specific functions and unique cellular targets. Coinfection with VSV and influenza virus resulted in the dramatic inhibition of influenza virus transcription; polyadenylated mRNAs corresponding to the influenza virus NP and NS1 proteins could not be detected by Northern blot analysis. However, reduced levels of the influenza virus replicative templates were still synthesized during double infection. Coinfection with VSV also resulted in the inhibition of influenza viral mRNA translation, even when superinfection with VSV was delayed until 3 or 6 hr after influenza virus infection. VSV required at least 2 hr to affect the inhibition of translation; this corresponded to the time after VSV infection when inhibition of cellular protein synthesis was evident. These results demonstrate that, in contrast to adenovirus, the VSV-mediated inhibition of cellular macromolecular synthesis may be effective against influenza virus.
Frielle
D W
DW
Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Kim
P B
PB
Keene
J D
JD
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000235:genetics*; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012326:RNA Splicing; D012342:RNA, Small Nuclear / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis; D014158:Transcription, Genetic; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics; D014777:Virus Diseases / Q000235:genetics*
D012342:RNA, Small Nuclear; D012367:RNA, Viral; D014764:Viral Proteins; D003609:Dactinomycin; D003513:Cycloheximide