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REVIEW article
Front. Cell. Infect. Microbiol.
Sec. Molecular Viral Pathogenesis
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1560250
PA and PA-X: two key proteins from segment 3 of the influenza viruses
Provisionally accepted- 1 Zhejiang Sci-Tech University, Hangzhou, China
- 2 College of Life Sciences, China Jiliang University, Hanghzou, Zhejiang Province, China
In recent years, the influenza viruses have posed an increasingly severe threat to public health. It is essential to analyze the virulence and pathogenesis of influenza viruses to prevent and control them, as well as create antiviral drugs. Previous studies have revealed that influenza virus segment 3 codes for not only the PA protein but also a novel protein, PA-X. PA protein is one subunit of the polymerase of influenza viruses and plays a critical role in its life cycle. PA presented endonuclease activity, the transcription and replication of the viral genome, viral virulence, protein degradation, and host immune response by interacting with viral proteins, including PB2, PB1, and host factors, including ANP32A, CHD6, HAX1, hCLE, HDAC6, MCM complex. PA mutations were involved in the viral replication, pathogenicity, and transmission of influenza viruses in poultry, mammals, and humans. PA-X is an open reading frame generated by +1 ribosomal code shift at the N-terminal amino acids of segment 3 and possesses the shutoff activity of host gene expression, regulating the host immune response, viral virulence and transmission. Therefore, PA is one ideal target for the development of antiviral drugs against influenza viruses. Baloxavir marboxil (BXM) and Favipiravir are two very effective antiinfluenza virus drugs targeting the PA endonuclease domain of influenza A viruses. In this review, we summarized the structures, viral replication, virulent determinants and transmission, host factors, innate immunity, and antiviral drugs involved in PA and PA-X. The information is of great value for underlying the mechanism of viral replication and developing novel effective strategies to prevent and control influenza infection and the pandemic.
Keywords: influenza viruses, PA, PA-X, host factors, Antiviral drugs, Host shutoff activity, Innate immunity Influenza viruses, innate immunity
Received: 14 Jan 2025; Accepted: 27 Feb 2025.
Copyright: © 2025 Zhang, Tao, Wu, Shu, He and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Huapeng Feng, Zhejiang Sci-Tech University, Hangzhou, China
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