The matrix protein of vesicular stomatitis virus inhibits host-directed transcription of target genes via interaction with the TFIIH subunit p8.

In response to viral infection, the host innate antiviral response is elicited to limit viral replication. Many viruses have evolved various strategies to circumvent the host antiviral response. It has been reported that matrix (M) protein of vesicular stomatitis virus (VSV) can inhibit host gene expression to evade the host innate immune response. However, the molecular mechanism remains unclear. Here, we demonstrated that VSV M protein inhibited transcription of a reporter gene transfected into BSR-T7/5 cells. To further investigate the underlying mechanism, a yeast two-hybrid screen was performed to search for host proteins that interact with the M protein. The subunit of transcription/repair factor TFIIH, p8, was identified as an M binding partner, and the interaction was validated with a GST pull-down assay and laser confocal microscopy. Through a mutagenesis analysis, we found that the p8-M interaction was impaired when I96, E156, R159 and R160 residues on M were replaced with Ala. These mutants reduced the inhibitory effect on transcription of the reporter gene. Furthermore, the transcription inhibition mediated by M was impaired when co-expressed with p8. These results indicate that the p8-M interaction plays an important role in inhibiting transcription of host genes.