OTUB1 contributes to the stability and function of Influenza A virus NS2.

Autor: Li YJ; Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan.; Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan., Chen CY; Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan., Kuo YS; Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan.; Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan., Huang YW; Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan.; Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan., Kuo RL; Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan., Chang LK; Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan., Yang JH; Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, New Taipei, Taiwan., Lai CH; Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan.; Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan., Shih SR; Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan., Chiu YF; Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan.; Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.; Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan.; Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, New Taipei, Taiwan.; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 May 30; Vol. 20 (5), pp. e1012279. Date of Electronic Publication: 2024 May 30 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012279
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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