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

• Published in: PloS one Vol. 8; no. 1; p. e53515
• Main Authors: Rodriguez, Ariel, Falcon, Ana, Cuevas, Maria Teresa, Pozo, Francisco, Guerra, Susana, García-Barreno, Blanca, Martinez-Orellana, Pamela, Pérez-Breña, Pilar, Montoya, Maria, Melero, Jose Antonio, Pizarro, Manuel, Ortin, Juan, Casas, Inmaculada, Nieto, Amelia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-01-2013; Public Library of Science (PLoS)
• Subjects: Adult; Adults; Alleles; Alveoli; Amino acids; Amino Acids - genetics; Animal models; Animals; Binding sites; Biological properties; Biology; CCR5 protein; Cell Line; Cells, Cultured; Children; Chronic illnesses; Cytokines; Cytokines - metabolism; Epithelial cells; Epithelial Cells - pathology; Epithelial Cells - virology; Female; Genetic aspects; Growth kinetics; Health aspects; Humans; Immunohistochemistry; Infections; Infectious diseases; Influenza; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - physiology; Influenza viruses; Influenza, Human - epidemiology; Influenza, Human - pathology; Influenza, Human - virology; Kinetics; Lungs; Medicine; Mice; Mice, Inbred BALB C; Morbidity; Mortality; Mutation; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; Pandemics; Pathogenicity; Pathogens; Patients; Pulmonary Alveoli - pathology; Pulmonary Alveoli - virology; Receptors, CCR5 - genetics; Respiratory diseases; Strains (organisms); Surveillance; Swine flu; Swine influenza; Viral Load; Virology; Virulence; Virulence (Microbiology); Virus diseases; Virus Replication; Viruses; Young adults; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053515

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).