RT Journal Article
T1 Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients.
A1 Vasilijevic, Jasmina
A1 Zamarreño, Noelia
A1 Oliveros, Juan Carlos
A1 Rodriguez-Frandsen, Ariel
A1 Gómez, Guillermo
A1 Rodriguez, Guadalupe
A1 Pérez-Ruiz, Mercedes
A1 Rey, Sonia
A1 Barba, Isabel
A1 Pozo, Francisco
A1 Casas, Inmaculada
A1 Nieto, Amelia
A1 Falcón, Ana
AB 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.
YR 2017
FD 2017-10-12
LK http://hdl.handle.net/10668/11675
UL http://hdl.handle.net/10668/11675
LA en
DS RISalud
RD Apr 5, 2025