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oai:repisalud.isciii.es:20.500.12105/67182024-09-27T23:09:38Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Vasilijevic, Jasmina author Zamarreño, Noelia author Oliveros, Juan Carlos author Rodriguez-Frandsen, Ariel author Gómez, Guillermo author Rodriguez, Guadalupe author Pérez-Ruiz, Mercedes author Rey, Sonia author Barba, Isabel author Pozo Sanchez, Francisco author Casas Flecha, Inmaculada author Nieto, Amelia author Falcon, Ana author 2017-10-12 Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-circulate with pandemic or epidemic viruses. Looking for potential virulence factors, we have identified a polymerase PA D529N mutation detected in a fatal IAV case, whose introduction into two different recombinant virus backbones, led to reduced defective viral genomes (DVGs) production. This mutation conferred low induction of antiviral response in infected cells and increased pathogenesis in mice. To analyze the association between low DVGs production and pathogenesis in humans, we performed a genomic analysis of viruses isolated from a cohort of previously healthy individuals who suffered highly severe IAV infection requiring admission to Intensive Care Unit and patients with fatal outcome who additionally showed underlying medical conditions. These viruses were compared with those isolated from a cohort of mild IAV patients. Viruses with fewer DVGs accumulation were observed in patients with highly severe/fatal outcome than in those with mild disease, suggesting that low DVGs abundance constitutes a new virulence pathogenic marker in humans. PLoS Pathog. 2017 Oct 12;13(10):e1006650. 10.1371/journal.ppat.1006650 1553-7374 1553-7374 PLoS pathogens 29023600 http://hdl.handle.net/20.500.12105/6718 Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients