title: Polymorphisms at residue 222 of the hemagglutinin of pandemic influenza A(H1N1)pdm09: association of quasi-species to morbidity and mortality in different risk categories.
abstract: The D222G substitution in the hemagglutinin (HA) gene of the pandemic influenza A(H1N1)pdm09 virus has been identified as a potential virulence marker, because this change allows for virus invasion deeper into the respiratory tract. In this study, we analyzed D, G and N polymorphisms at residue 222 by pyrosequencing (PSQ). We initially analyzed 401 samples from Brazilian patients. These were categorized with respect to clinical conditions due to influenza infection (mild, serious or fatal) and sub-stratified by risky factors. The frequency of mixed population of virus, with more than one polymorphism at residue 222, was significantly higher in serious (10.6%) and fatal (46.7%) influenza cases, whereas those who showed mild influenza infections were all infected by D222 wild-type. Mixtures of quasi-species showed a significant association of mortality, especially for those with risk factors, in special pregnant women. These results not only reinforce the association between D222G substitution and influenza A(H1N1)pdm09-associated morbidity and mortality, but also add the perspective that a worse clinical prognosis is most likely correlated with mixtures of quasi-species at this HA residue. Therefore, quasi-species may have a critical and underestimated role in influenza-related clinical outcomes.
authors.affiliation: Laboratório de Vírus Respiratórios e do Sarampo, Instituto Oswaldo Cruz/ FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Paola Cristina
authors.initials: PC
authors.lastname: Resende
authors.affiliation: Laboratório de Vírus Respiratórios e do Sarampo, Instituto Oswaldo Cruz/ FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Motta
authors.affiliation: Laboratório de Vírus Respiratórios e do Sarampo, Instituto Oswaldo Cruz/ FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Maria de Lourdes A
authors.initials: Mde L
authors.lastname: Oliveira
authors.affiliation: Laboratório Central de Saúde Pública do Estado do Rio de Grande do Sul -Fundação estadual de produção e pesquisa em saúde seção de virologia, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Gregianini
authors.affiliation: Laboratório Central de Saúde Pública do Estado de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Sandra B
authors.initials: SB
authors.lastname: Fernandes
authors.affiliation: Laboratório Central de Saúde Pública do Estado de Minas Gerais/Instituto Octávio Magalhães e Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ana Luisa F
authors.initials: AL
authors.lastname: Cury
authors.affiliation: Laboratório Central de Saúde Pública do Estado do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Maria
authors.initials: M
authors.lastname: do Carmo D Rosa
authors.affiliation: Laboratório de Vírus Respiratórios e do Sarampo, Instituto Oswaldo Cruz/ FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Thiago Moreno L
authors.initials: TM
authors.lastname: Souza
authors.affiliation: Laboratório de Vírus Respiratórios e do Sarampo, Instituto Oswaldo Cruz/ FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marilda M
authors.initials: MM
authors.lastname: Siqueira
mesh_terms: D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000235:genetics / Q000401:mortality; D008297:Male; D058873:Pandemics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000235:genetics / Q000401:mortality; D012307:Risk Factors
chemical_list: C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus