Vesicular Stomatitis Virus Transcription Is Inhibited by TRIM69 in the Interferon-Induced Antiviral State.

摘要: Interferons (IFNs) induce the expression of interferon-stimulated genes (ISGs), many which are responsible for cellular antiviral state in replication numerous viruses is blocked. How majority individual ISGs inhibit particular unknown. We conducted a loss-of-function screen to identify required activity alpha interferon (IFN-α) against vesicular stomatitis virus, Indiana serotype (VSVIND), prototype negative-strand RNA virus. Our revealed that TRIM69, member tripartite motif (TRIM) family proteins, VSVIND inhibitor. TRIM69 potently inhibited through previously undescribed transcriptional inhibition mechanism. Specifically, physically associates with phosphoprotein (P), requiring specific peptide target sequence encoded therein. P cofactor viral polymerase and synthesis, as well assembly compartments. By targeting P, inhibits pioneer transcription incoming virion-associated minus-strand RNA, thereby preventing synthesis mRNAs, consequently impedes all downstream events cycle. Unlike some TRIM does not by inducing degradation proteins. Rather, higher-order multimerization its activity, suggesting functions sequestration or anatomical disruption machinery synthesis.IMPORTANCE important cytokines work hundreds host whose products viruses. While has long been known, identities mechanisms action most interferon-induced proteins remain be discovered. identified gene virus (VSV), model genome consists single molecule negative-sense polarity. found protein, molecular interacts function (P) component machinery, messenger RNAs.