Publication: Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients.
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Identifiers
Date
2017-10-12
Authors
Vasilijevic, Jasmina
Zamarreño, Noelia
Oliveros, Juan Carlos
Rodriguez-Frandsen, Ariel
Gómez, Guillermo
Rodriguez, Guadalupe
Pérez-Ruiz, Mercedes
Rey, Sonia
Barba, Isabel
Pozo, Francisco
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
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.
Description
MeSH Terms
Adolescent
Adult
Animals
Child
Child, Preschool
Female
Genome, Viral
Humans
Influenza A Virus, H1N1 Subtype
Influenza A Virus, H5N1 Subtype
Influenza, Human
Male
Mice
Middle Aged
Orthomyxoviridae Infections
Virulence
Virus Replication
Young Adult
Adult
Animals
Child
Child, Preschool
Female
Genome, Viral
Humans
Influenza A Virus, H1N1 Subtype
Influenza A Virus, H5N1 Subtype
Influenza, Human
Male
Mice
Middle Aged
Orthomyxoviridae Infections
Virulence
Virus Replication
Young Adult