Characterization in vitro and in vivo of a pandemic H1N1 influenza virus from a fatal case

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 p...

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Detalhes bibliográficos
Autores: Rodriguez, Ariel, Falcon, Ana, Cuevas, Maria Teresa, Pozo Sanchez, Francisco, Guerra, Susana, Garcia-Barreno, Blanca, Martínez-Orellana, Pamela, Perez-Breña, Pilar, Montoya, Maria, Melero, Jose Antonio, Pizarro, Manuel, Ortin, Juan, Casas Flecha, Inmaculada, Nieto, Amelia
Formato: artículo
Fecha de publicación:2013
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6637
Acesso em linha:http://hdl.handle.net/20.500.12105/6637
Access Level:acceso abierto
Palavra-chave:Adult
Alleles
Amino Acids
Animals
Cell Line
Cells, Cultured
Cytokines
Epithelial Cells
Female
Humans
Immunohistochemistry
Influenza A Virus, H1N1 Subtype
Influenza, Human
Mice
Mice, Inbred BALB C
Orthomyxoviridae Infections
Pulmonary Alveoli
Receptors, CCR5
Viral Load
Virus Replication
Pandemics
Descrição
Resumo: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).