Vesicular stomatitis virus matrix protein inhibits host cell-directed transcription of target genes in vivo.
Infection by vesicular stomatitis virus (VSV) results in a rapid inhibition of host cell transcription and translation. To determine whether the viral matrix (M) protein was involved in this inhibition of host cell gene expression, an M protein expression vector was cotransfected with a target gene vector, encoding the target gene, encoding chloramphenicol acetyltransferase (CAT). Expression of M protein caused a decrease in CAT activity in a gene dosage-dependent manner, and inhibition was apparent by 12 h posttransfection. The inhibitory effect of M protein was quite potent. The level of M protein required for a 10-fold inhibition of CAT activity was less than 1% of the level of M protein produced during the sixth hour of VSV infection. Northern (RNA) analysis of cotransfected cells showed that expression of M protein caused a reduction in the steady-state level of the vector-encoded mRNAs. Expression of both CAT and M mRNAs was reduced in cells cotransfected with a plasmid encoding M protein, indicating that expression of small amounts of M protein from plasmid DNA inhibits further expression of both M and CAT mRNAs. Nuclear runoff transcription analysis demonstrated that expression of M protein inhibited transcription of the target genes. This is the first report of a viral gene product which is capable of inhibiting transcription in vivo in the absence of any other viral component.
Black
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BL
Department of Microbiology and Immunology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157.
Lyles
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DS
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004279:DNA, Viral; D005822:Genetic Vectors; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*
D004279:DNA, Viral; D012333:RNA, Messenger; D014763:Viral Matrix Proteins; D015500:Chloramphenicol O-Acetyltransferase