Vesicular stomatitis virus matrix protein inhibits host cell gene expression by targeting the nucleoporin Nup98

Vesicular stomatitis virus matrix protein (VSV M) has been shown to inhibit both transcription and nucleocytoplasmic transport. We have isolated a mut ant form of M, termed M(D), lacking both inhibitory activities. HeLa cells expressing M, but not M(D), accumulate polyadenylated RNAs within the nucle us. Concomitantly, a fraction of M, but not of the M(D) mutant, localizes a t the nuclear rim. Additionally, the nucleoporin Nup98 specifically interac ts with M but not with M(D). In Nop98(-/-) cells, both the levels of M at t he nuclear envelope and its inhibitory effects on host cell-directed expres sion of reporter genes were significantly reduced. Together, our data demon strate that VSV M inhibits host cell gene expression by targeting a nucleop orin and primarily blocking nuclear export.