Rodriguez, ArielFalcon, AnaCuevas, Maria TeresaPozo Sanchez, FranciscoGuerra, SusanaGarcia-Barreno, BlancaMartínez-Orellana, PamelaPerez-Breña, PilarMontoya, MariaMelero, Jose AntonioPizarro, ManuelOrtin, JuanCasas Flecha, InmaculadaNieto, Amelia2018-11-202018-11-202013-01-10PLoS One. 2013;8(1):e535151932-6203http://hdl.handle.net/20.500.12105/6637Pandemic 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).engVoRhttp://creativecommons.org/licenses/by/4.0/AdultAllelesAmino AcidsAnimalsCell LineCells, CulturedCytokinesEpithelial CellsFemaleHumansImmunohistochemistryInfluenza A Virus, H1N1 SubtypeInfluenza, HumanMiceMice, Inbred BALB COrthomyxoviridae InfectionsPulmonary AlveoliReceptors, CCR5Viral LoadVirus ReplicationPandemicsAtribución 4.0 Internacional2332644781e5351510.1371/journal.pone.00535151932-6203PloS oneopen access