1. Natural Selection of H5N1 Avian Influenza A Viruses with Increased PA-X and NS1 Shutoff Activity
- Author
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Laura Villamayor, Marta L. DeDiego, Luis Martinez-Sobrido, Javier Ortego, Aitor Nogales, Sergio Utrilla-Trigo, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Nogales, Aitor, Utrilla-Trigo, Sergio (0000-0002-7672-7658), Ortego, Javier (0000-0002-4275-7277), Martinez-Sobrido, Luis (0000-0001-7084-0804), and DeDiego, Marta L.(0000-0002-7888-7372)
- Subjects
Male ,NS1 ,Virulence ,Biology ,Viral Nonstructural Proteins ,medicine.disease_cause ,Virus Replication ,Microbiology ,Virus ,Article ,shutoff ,Birds ,Mice ,Orthomyxoviridae Infections ,Virology ,Gene expression ,Influenza, Human ,Influenza A virus ,medicine ,influenza A virus ,Animals ,Humans ,Selection, Genetic ,Innate immune system ,Influenza A Virus, H5N1 Subtype ,Host (biology) ,H5N1 ,Influenza A virus subtype H5N1 ,QR1-502 ,Immunity, Innate ,Repressor Proteins ,Infectious Diseases ,PA-X ,HEK293 Cells ,Viral replication ,Influenza in Birds ,Host-Pathogen Interactions ,HPAIV ,Female ,Interferons - Abstract
25 Pág. Centro de Investigación en Sanidad Animal (CISA), Influenza A viruses (IAV) can infect a broad range of mammalian and avian species. However, the host innate immune system provides defenses that restrict IAV replication and infection. Likewise, IAV have evolved to develop efficient mechanisms to counteract host antiviral responses to efficiently replicate in their hosts. The IAV PA-X and NS1 non-structural proteins are key virulence factors that modulate innate immune responses and virus pathogenicity during infection. To study the determinants of IAV pathogenicity and their functional co-evolution, we evaluated amino acid differences in the PA-X and NS1 proteins of early (1996–1997) and more recent (since 2016) H5N1 IAV. H5N1 IAV have zoonotic and pandemic potential and represent an important challenge both in poultry farming and human health. The results indicate that amino acid changes occurred over time, affecting the ability of these two non-structural H5N1 IAV proteins to inhibit gene expression and affecting virus pathogenicity. These results highlight the importance to monitor the evolution of these two virulence factors of IAV, which could result in enhanced viral replication and virulence., This work was supported with funds from Comunidad de Madrid (Spain), reference 2017-T1/BMD-5155 and the Spanish Ministry of Science, Innovation and Universities (RTI-2018-094213-A-I00) to M.L.D and a “Ramon y Cajal” Incorporation grant (RYC-2017) from Spanish Ministry of Science, Innovation and Universities to A.N.
- Published
- 2021