Publication: Chunfu Zheng lab, Journal of Virology

On September 22th, 2016, researchers at Dr. Chunfu Zheng’s group published an article entitled “Herpes Simplex Virus 1 Tegument Protein UL41 Counteracts IFIT3 Antiviral Innate Immunity” in Journal of Virology. This study identifies IFIT3 as a novel target of the tegument protein UL41 with the activity of endonuclease for the first time and provides new insight into HSV-1 mediated immune evasion.

Humans have a distinct combination of IFIT family genes, including IFIT1 (ISG56), IFIT2 (ISG54), IFIT3 (ISG60), and IFIT5 (ISG58), which are clustered on human chromosome 10. Among these IFIT family genes, IFIT3 has been demonstrated to inhibit the replication of many DNA and RNA viruses. Host antiviral responses are significantly boosted or crippled in the presence or absence of IFIT3, however, whether IFIT3 plays a role during HSV-1 infection is still unknown. In this study, we demonstrated for the first time that ectopically expressed IFIT3 could restrict the replication of vesicular stomatitis virus (VSV), but had little effect on the replication of wild-type (WT)-HSV-1. Further study showed that WT-HSV-1 infection down-regulated the e­xpression of IFIT3, and ectopic e­xpression of UL41 notably reduced the e­xpression of IFIT3. The ectopic e­xpression of IFIT3 could restrain the replication of UL41-mutant HSV-1 and knockdown of IFIT3did facilitate its replication. The underlying molecular mechanism is that the tegument protein UL41 of HSV-1 decreases the accumulation of IFIT3 mRNA and reduces the protein e­xpression of IFIT3 to subvert its antiviral activity. Findings in this study will help broaden our insight into the mechanisms applied by HSV-1 to dampen host antiviral responses and facilitate its persistence.

Mr. Zhangtao Jiang and Ms. Chenhe Su are the co-first authors; Prof. Chunfu Zheng is the corresponding author.