PA-X is a fusion protein encoded by a +1 frameshifted open reading frame (X-ORF) in PA gene. The X-ORF can be translated in full-length (61 amino acids, aa) or truncated (41 aa) form. However, the role of C-Terminal 20 aa of PA-X in virus function has not yet been fully elucidated. To this end, we constructed the contemporary influenza viruses with full and truncated PA-X by reverse genetics to compare their replication and pathogenicity. The full-length PA-X virus in MDCK and human A549 cells conferred 10- to 100-fold increase in viral replication, and more virulent and caused more severe inflammatory responses in mice relative to corresponding truncated PA-X virus, suggesting that the terminal 20 aa could play a role in enhancing viral replication and contribute to virulence.
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http://dx.doi.org/10.1016/j.vetmic.2020.108916 | DOI Listing |
Virulence
December 2025
Key Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou, China.
Several viruses, including influenza A virus (IAV), encode viral factors to hijack cellular RNA biogenesis processes to direct the degradation of host mRNAs, termed "host shutoff." Host shutoff enables viruses to simultaneously reduce antiviral responses and provides preferential access for viral mRNAs to cellular translation machinery. IAV PA-X is one of these factors that selectively shuts off the global host genes.
View Article and Find Full Text PDFJ Med Virol
August 2024
Department of Medicine, School of Medicine, University of Connecticut Health Center, Division of Nephrology, Farmington, Connecticut, USA.
Seasonal H3N2 influenza virus, known for its rapid evolution, poses a serious threat to human health. This study focuses on analyzing the influenza virus trends in Jining City (2018-2023) and understanding the evolving nature of H3N2 strains. Data on influenza-like cases were gathered from Jining City's sentinel hospitals: Jining First People's Hospital and Rencheng Maternal and Child Health Hospital, using the Chinese Influenza Surveillance Information System.
View Article and Find Full Text PDFLive-attenuated influenza vaccines (LAIV) offer advantages over the commonly used inactivated split influenza vaccines. However, finding the optimal balance between sufficient attenuation and immunogenicity has remained a challenge. We recently developed an alternative LAIV based on the 2009 pandemic H1N1 virus with a truncated NS1 protein and lacking PA-X protein expression (NS1(1-126)-ΔPAX).
View Article and Find Full Text PDFViruses
May 2024
Southern African Foundation for the Conservation of Coastal Birds (SANCCOB), Cape Town 7441, South Africa.
In 2023, South Africa continued to experience sporadic cases of clade 2.3.4.
View Article and Find Full Text PDFPLoS Comput Biol
April 2024
Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised. We provide detailed predictions of the key locations within these packaging-associated regions, and their structures, by applying a recently-improved pipeline for delineating constrained regions in RNA viruses and applying structural prediction algorithms. We find and characterise other known constrained regions within influenza A genomes, including the region associated with the PA-X frameshift, regions associated with alternative splicing, and constraint around the initiation motif for a truncated PB1 protein, PB1-N92, associated with avian viruses.
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