title: Characterization in vitro and in vivo of a pandemic H1N1 influenza virus from a fatal case.
abstract: Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32).
authors: Centro Nacional de Biotecnología, C.S.I.C. Darwin 3, Cantoblanco, Madrid, Spain.
authors: Ariel
authors: A
authors: Rodriguez
authors: Ana
authors: A
authors: Falcon
authors: Maria Teresa
authors: MT
authors: Cuevas
authors: Francisco
authors: F
authors: Pozo
authors: Susana
authors: S
authors: Guerra
authors: Blanca
authors: B
authors: García-Barreno
authors: Pamela
authors: P
authors: Martinez-Orellana
authors: Pilar
authors: P
authors: Pérez-Breña
authors: Maria
authors: M
authors: Montoya
authors: Jose Antonio
authors: JA
authors: Melero
authors: Manuel
authors: M
authors: Pizarro
authors: Juan
authors: J
authors: Ortin
authors: Inmaculada
authors: I
authors: Casas
authors: Amelia
authors: A
authors: Nieto
mesh_terms: D000328:Adult; D000483:Alleles; D000596:Amino Acids / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000473:pathology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000821:virology; D058873:Pandemics; D011650:Pulmonary Alveoli / Q000473:pathology / Q000821:virology; D019713:Receptors, CCR5 / Q000235:genetics; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000596:Amino Acids; D016207:Cytokines; D019713:Receptors, CCR5