The interferon-inducible protein TDRD7 inhibits AMP-activated protein kinase and thereby restricts autophagy-independent virus replication
| Autor: | Sukanya Chakravarty, R. Travis Taylor, Sonam Popli, Gayatri Subramanian, Saurabh Chattopadhyay, Ritu Chakravarti |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
viruses Immunology Herpesvirus 1 Human AMP-Activated Protein Kinases Virus Replication Biochemistry Virus Mice 03 medical and health sciences Viral entry Interferon Chlorocebus aethiops Autophagy medicine Animals Humans Protein kinase A Vero Cells Molecular Biology 030102 biochemistry & molecular biology biology AMPK Cell Biology biology.organism_classification Sendai virus Cell biology 030104 developmental biology Ribonucleoproteins Viral replication HeLa Cells medicine.drug |
| Zdroj: | J Biol Chem |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra120.013533 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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