Genomic signatures and antiviral drug susceptibility profile of A(H1N1)pdm09

Autor: Marta Gíria, Sónia Pedro, Helena Rebelo de Andrade, Luís A. Santos, Madalena Almeida Santos, Vanessa Correia
Rok vydání: 2011
Předmět:
viruses
chemistry.chemical_compound
Influenza A Virus
H1N1 Subtype
Pregnancy
Pregnancy Complications
Infectious
Child
Phylogeny
Genetics
0303 health sciences
biology
Virulence
Resistência aos Antimicrobianos
virus diseases
Genomics
3. Good health
Infectious Diseases
A(H1N1)pdm09
Viral evolution
Child
Preschool
Female
Host adaptation
Antiviral Drug Susceptibility
medicine.drug
Oseltamivir
Adolescent
medicine.drug_class
Genome
Viral
Microbial Sensitivity Tests
Antiviral Agents
Risk Assessment
Cell Line
03 medical and health sciences
Viral Proteins
Zanamivir
Internal Proteins
Virology
Drug Resistance
Viral
Influenza
Human
medicine
Animals
Humans
Point Mutation
030304 developmental biology
Portugal
030306 microbiology
Point mutation
Viral Fitness
chemistry
biology.protein
Antiviral drug
Neuraminidase
Zdroj: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 53(2)
ISSN: 1873-5967
Popis: 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.
Databáze: OpenAIRE
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