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 pro...

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Bibliographic Details
Published in:	Journal of clinical virology Vol. 53; no. 2; pp. 140 - 144
Main Authors:	Gíria, Marta Tiago, Rebelo de Andrade, Helena, Santos, Luís André, Correia, Vanessa Martins, Pedro, Sónia Vicente, Santos, Madalena Almeida
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 01-02-2012 Elsevier
Subjects:	A(H1N1)pdm09 Adolescent Allergy and Immunology Animals Antiviral Agents - pharmacology Antiviral drug susceptibility Biological and medical sciences Cell Line Child Child, Preschool Drug Resistance, Viral Female Fundamental and applied biological sciences. Psychology Genome, Viral - genetics Genomics Human viral diseases Humans Infectious Disease Infectious diseases Influenza A Virus, H1N1 Subtype - drug effects Influenza A Virus, H1N1 Subtype - genetics Influenza A Virus, H1N1 Subtype - pathogenicity Influenza A Virus, H1N1 Subtype - physiology Influenza, Human - epidemiology Influenza, Human - pathology Influenza, Human - virology Internal proteins Medical sciences Microbial Sensitivity Tests Microbiology Miscellaneous Phylogeny Point Mutation Portugal - epidemiology Pregnancy Pregnancy Complications, Infectious - epidemiology Pregnancy Complications, Infectious - pathology Pregnancy Complications, Infectious - virology Risk Assessment Viral diseases Viral fitness Viral Proteins - genetics Virology Virulence Portugal A(H1N1)pdm09 Antiviral drug susceptibility Internal proteins Viral fitness Virulence Risk assessment Sensitivity Genomics Antiviral Protein Fitness
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Summary:	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. Study design 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. Discussion 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1386-6532 1873-5967
DOI:	10.1016/j.jcv.2011.11.002