Type-IInterferon-Inducible SERTAD3 Inhibits Influenza A Virus Replication by Blocking the Assembly of Viral RNA Polymerase Complex.

Abstract

Influenza A virus (IAV) infection stimulates a type I interferon (IFN-I) response in host cells that exerts antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). However, most ISGs are poorly studied for their roles in the infection of IAV. Herein, we demonstrate that SERTA domain containing 3 (SERTAD3) has a significant inhibitory effect on IAV replication in vitro. More importantly, Sertad3-/- mice develop more severe symptoms upon IAV infection. Mechanistically, we find SERTAD3 reduces IAV replication through interacting with viral polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), and polymerase acidic protein (PA) to disrupt the formation of the RNA-dependent RNA polymerase (RdRp) complex. We further identify an 8-amino-acid peptide of SERTAD3 as a minimum interacting motif that can disrupt RdRp complex formation and inhibit IAV replication. Thus, our studies not only identify SERTAD3 as an antiviral ISG, but also provide the mechanism of potential application of SERTAD3-derived peptide in suppressing influenza replication.

• Authors: Nina Sun, Chunfeng Li, Xiao-Feng Li, Yong-Qiang Deng, Tao Jiang, Na-Na Zhang, Shulong Zu, Rong-Rong Zhang, Lili Li, Xiang Chen, Ping Liu, Sarah Gold, Ning Lu, Peishuang Du, Jingfeng Wang, Cheng-Feng Qin, Genhong Cheng
• Journal: Cell reports (Cell Rep) Vol. 33 Issue 5 Pg. 108342 (11 03 2020) ISSN: 2211-1247 [Electronic] United States
• PMID: 33147462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Interferon Type I
• Peptides
• Protein Subunits
• SERTAD3 protein, human
• Sertad3 protein, mouse
• Trans-Activators
• Viral Replicase Complex Proteins

Topics

• A549 Cells
• Animals
• Dogs
• HEK293 Cells
• Humans
• Influenza A virus (drug effects, enzymology, physiology)
• Interferon Type I (metabolism)
• Madin Darby Canine Kidney Cells
• Mice, Inbred C57BL
• Mice, Knockout
• Peptides (pharmacology)
• Protein Binding (drug effects)
• Protein Subunits (metabolism)
• Trans-Activators (metabolism)
• Viral Replicase Complex Proteins (metabolism)
• Virus Replication (drug effects, physiology)