OTUB1 Contributes to the Stability and Function of Influenza A Virus NS2

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2024 May 30

PMID 38814988

Authors

Yu-Jyun Li

Chi-Yuan Chen

Yu-Shen Kuo

Yi-Wen Huang

Rei-Lin Kuo

Li-Kwan Chang

Jeng-How Yang

Chih-Ho Lai

Shin-Ru Shih

Ya-Fang Chiu

Affiliations

Soon will be listed here.

Abstract

The influenza A virus (IAV) consists of 8 single-stranded, negative-sense viral RNA (vRNA) segments. After infection, vRNA is transcribed, replicated, and wrapped by viral nucleoprotein (NP) to form viral ribonucleoprotein (vRNP). The transcription, replication, and nuclear export of the viral genome are regulated by the IAV protein, NS2, which is translated from spliced mRNA transcribed from viral NS vRNA. This splicing is inefficient, explaining why NS2 is present in low abundance after IAV infection. The levels of NS2 and its subsequent accumulation are thought to influence viral RNA replication and vRNP nuclear export. Here we show that NS2 is ubiquitinated at the K64 and K88 residues by K48-linked and K63-linked polyubiquitin (polyUb) chains, leading to the degradation of NS2 by the proteasome. Additionally, we show that a host deubiquitinase, OTUB1, can remove polyUb chains conjugated to NS2, thereby stabilizing NS2. Accordingly, knock down of OTUB1 by siRNA reduces the nuclear export of vRNP, and reduces the overall production of IAV. These results collectively demonstrate that the levels of NS2 in IAV-infected cells are regulated by a ubiquitination-deubiquitination system involving OTUB1 that is necessary for optimal IAV replication.

Citing Articles

Phosphorylation of S-S-S Motif in Nuclear Export Protein (NEP) Plays a Critical Role in Viral Ribonucleoprotein (vRNP) Nuclear Export of Influenza A and B Viruses.

Liu X, Yang C, Lin X, Sun X, Chen H, Zhang Q Adv Sci (Weinh). 2024; 12(2):e2309477.

PMID: 39575547 PMC: 11727112. DOI: 10.1002/advs.202309477.

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