title: Phylogenetic analyses of influenza A (H1N1)pdm09 hemagglutinin gene during and after the pandemic event in Brazil.
abstract: Pandemic influenza A H1N1 [A(H1N1)pdm09] was first detected in Brazil in May 2009, and spread extensively throughout the country causing a peak of infection during June to August 2009. Since then, it has continued to circulate with a seasonal pattern, causing high rates of morbidity and mortality. Over this period, the virus has continually evolved with the accumulation of new mutations. In this study we analyze the phylogenetic relationship in a collection of 220 A(H1N1)pdm09 hemagglutinin (HA) gene sequences collected during and after the pandemic period (2009 to 2014) in Brazil. In addition, we have looked for evidence of viral polymorphisms associated with severe disease and compared the range of viral variants with the vaccine strain (A/California/7/2009) used throughout this period. The phylogenetic analyses in this study revealed the circulation of at least eight genetic groups in Brazil. Two (G6-pdm and G7-pdm) co-circulated during the pandemic period, showing an early pattern of viral diversification with a low genetic distance from vaccine strain. Other phylogenetic groups, G5, G6 (including 6B, 6C and 6D subgroups), and G7 were found in the subsequent epidemic seasons from 2011 to 2014. These viruses exhibited more amino acid differences from the vaccine strain with several substitutions at the antigenic sites. This is associated with a theoretical decrease in the vaccine efficacy. Furthermore, we observed that the presence of any polymorphism at residue 222 of the HA gene was significantly associated with severe/fatal cases, reinforcing previous reports that described this residue as a potential virulence marker. This study provides new information about the circulation of some viral variants in Brazil, follows up potential genetic markers associated with virulence and allows infer if the efficacy of the current vaccine against more recent A(H1N1)pdm09 strains may be reduced.
authors.affiliation: Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil. Electronic address: paola@ioc.fiocruz.br.
authors.forename: Paola Cristina
authors.initials: PC
authors.lastname: Resende
authors.affiliation: Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Fernando Couto
authors.initials: FC
authors.lastname: Motta
authors.affiliation: Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Priscila Silva
authors.initials: PS
authors.lastname: Born
authors.affiliation: Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil; Fondation Mérieux, Emerging Pathogens Laboratory, Centre International de Recherche en Infectologie (CIRI), Lyon, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Machado
authors.affiliation: Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Braulia Costa
authors.initials: BC
authors.lastname: Caetano
authors.affiliation: Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.affiliation: Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Marilda Mendonça
authors.initials: MM
authors.lastname: Siqueira
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001938:Brazil / Q000453:epidemiology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification* / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063868:Patient Outcome Assessment; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: A(H1N1)pdm09; Hemagglutinin; Influenza; Phylogenetic analyses; Quasispecies; Sequencing