title: Genomic signatures and antiviral drug susceptibility profile of A(H1N1)pdm09.
abstract: BACKGROUND
  Genetic changes in influenza surface and internal genes can alter viral fitness and virulence. Mutation trend analysis and antiviral drug susceptibility profiling of A(H1N1)pdm09 viruses is essential for risk assessment of emergent strains and disease management.
  
  
  OBJECTIVE
  To profile genomic signatures and antiviral drug resistance of A(H1N1)pdm09 viruses and to discuss the potential role of mutated residues in human host adaptation and virulence.
  
  
  METHODS
  A(H1N1)pdm09 viruses circulating in Portugal during pandemic and post-pandemic periods and 2009/2010 season. Viruses were isolated in MDCK-SIAT1 cell culture and subjected to mutation analysis of surface and internal proteins, and to antiviral drug susceptibility profiling.
  
  
  RESULTS
  The A(H1N1)pdm09 strains circulating during the epidemic period in Portugal were resistant to amantadine. The majority of the strains were found to be susceptible to oseltamivir and zanamivir, with five outliers to neuraminidase inhibitors (NAIs) identified. Specific mutation patterns were detected within the functional domains of internal proteins PB2, PB1, PA, NP, NS1, M1 and NS2/NEP, which were common to all isolates and also some cluster-specific.
  
  
  CONCLUSIONS
  Modification of viral genome transcription, replication and apoptosis kinetics, changes in antigenicity and antiviral drug susceptibility are known determinants of virulence. We report several point mutations with putative roles in viral fitness and virulence, and discuss their potential to result in more virulent phenotypes. Monitoring of specific mutations and genetic patterns in influenza viral genes is essential for risk assessing emergent strains, disease epidemiology and public health implications.
authors.affiliation: CPM-URIA, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Marta Tiago
authors.initials: MT
authors.lastname: Gíria
authors.forename: Helena
authors.initials: H
authors.lastname: Rebelo de Andrade
authors.forename: Luís André
authors.initials: LA
authors.lastname: Santos
authors.forename: Vanessa Martins
authors.initials: VM
authors.lastname: Correia
authors.forename: Sónia Vicente
authors.initials: SV
authors.lastname: Pedro
authors.forename: Madalena Almeida
authors.initials: MA
authors.lastname: Santos
mesh_terms: D000293:Adolescent; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D016679:Genome, Viral / Q000235:genetics*; D023281:Genomics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D007251:Influenza, Human / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D017354:Point Mutation; D011174:Portugal / Q000453:epidemiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D018570:Risk Assessment; D014764:Viral Proteins / Q000235:genetics*; D014774:Virulence
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins