The interferon-inducible protein TDRD7 inhibits AMP-activated protein kinase and thereby restricts autophagy-independent virus replication

Gayatri Subramanian, Sonam Popli, Sukanya Chakravarty, R. Travis Taylor, Ritu Chakravarti, Saurabh Chattopadhyay

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The interferon system is the first line of defense against virus infection. Recently, using a high-throughput genetic screen of a human interferon-stimulated gene short-hairpin RNA library, we identified a viral restriction factor, TDRD7 (Tudor domain–containing 7). TDRD7 inhibits the paramyxo-/pneumoviruses (e.g. Sendai virus and respiratory syncytial virus) by interfering with the virus-induced cellular autophagy pathway, which these viruses use for their replication. Here, we report that TDRD7 is a viral restriction factor against herpes simplex virus (HSV-1). Using knockdown, knockout, and ectopic expression systems, we demonstrate the anti–HSV-1 activity of TDRD7 in multiple human and mouse cell types. TDRD7 inhibited the virus-activated AMP-activated protein kinase (AMPK), which was essential for HSV-1 replication. Genetic ablation or chemical inhibition of AMPK activity suppressed HSV-1 replication in multiple human and mouse cells. Mechanistically, HSV-1 replication after viral entry depended on AMPK but not on its function in autophagy. The antiviral activity of TDRD7 depended on its ability to inhibit virus-activated AMPK. In summary, our results indicate that the newly identified viral restriction factor TDRD7 inhibits AMPK and thereby blocks HSV-1 replication independently of the autophagy pathway. These findings suggest that AMPK inhibition represents a potential strategy to manage HSV-1 infections.

Original languageEnglish
Pages (from-to)6811-6822
Number of pages12
JournalJournal of Biological Chemistry
Volume295
Issue number20
DOIs
StatePublished - May 15 2020

Bibliographical note

Publisher Copyright:
© 2020 Subramanian et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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