Giuseppe
Emeritus
The Genetic Makeup of Amantadine-Resistant and Oseltamivir-Resistant Human Influenza A/H1N1 Viruses. (J Clin Microbiol., abstract, edited)
3. J Clin Microbiol. 2010 Feb 3. [Epub ahead of print]
The Genetic Makeup of Amantadine-Resistant and Oseltamivir-Resistant Human Influenza A/H1N1 Viruses.
Zaraket H, Saito R, Suzuki Y, Baranovich T, Dapat C, Caperig-Dapat I, Suzuki H. - Division of Public Health, Department of Infectious Disease Control and International Medicine, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan.
The emergence and wide-spread of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1, is a major concern. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses we performed full genome sequencing of pre-pandemic A/H1N1 strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses, obtained from several areas in Japan during the 2007-08 and 2008-09 seasons, were analyzed. Full genome sequencing of these viruses was performed and phylogenetic relationships among each individual genome segment's sequences were inferred. Reference genome sequences from the Influenza Virus Resource database were included to determine the closest ancestor for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant strain has evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-08 season by acquiring the H275Y resistance conferring mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the Northern European resistant lineage) represented 100% of the H1N1 isolates from the 2008-09 season and further acquired at least one mutation in each of the PB2, PB1, HA, and NA genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages followed by the H275Y substitution in the NA and other mutations elsewhere in the genome contributed to the emergence of the oseltamivir-resistant lineage. On the other hand, amantadine-resistant viruses from the 2007-08 season distinctly clustered in clade 2C and were characterized by extensive amino acid substitutions across their genomes, suggesting that a fitness gap among its genetic components might have driven these mutations to maintain it in the population.
PMID: 20129961 [PubMed - as supplied by publisher]
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3. J Clin Microbiol. 2010 Feb 3. [Epub ahead of print]
The Genetic Makeup of Amantadine-Resistant and Oseltamivir-Resistant Human Influenza A/H1N1 Viruses.
Zaraket H, Saito R, Suzuki Y, Baranovich T, Dapat C, Caperig-Dapat I, Suzuki H. - Division of Public Health, Department of Infectious Disease Control and International Medicine, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan.
The emergence and wide-spread of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1, is a major concern. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses we performed full genome sequencing of pre-pandemic A/H1N1 strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses, obtained from several areas in Japan during the 2007-08 and 2008-09 seasons, were analyzed. Full genome sequencing of these viruses was performed and phylogenetic relationships among each individual genome segment's sequences were inferred. Reference genome sequences from the Influenza Virus Resource database were included to determine the closest ancestor for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant strain has evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-08 season by acquiring the H275Y resistance conferring mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the Northern European resistant lineage) represented 100% of the H1N1 isolates from the 2008-09 season and further acquired at least one mutation in each of the PB2, PB1, HA, and NA genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages followed by the H275Y substitution in the NA and other mutations elsewhere in the genome contributed to the emergence of the oseltamivir-resistant lineage. On the other hand, amantadine-resistant viruses from the 2007-08 season distinctly clustered in clade 2C and were characterized by extensive amino acid substitutions across their genomes, suggesting that a fitness gap among its genetic components might have driven these mutations to maintain it in the population.
PMID: 20129961 [PubMed - as supplied by publisher]
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