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Isolation of amantadine-resistant influenza a viruses (H3N2) from patients following administration of amantadine in Japan.

ABSTRACT: In Japan, the use of amantadine for treatment of influenza A virus infection was not accepted until November 1998, although it was widely used for treatment of Parkinsonism. Since then, we have monitored the emergence of amantadine-resistant viruses and isolated two viruses from patients on long-term treatment with amantadine.

SUBMITTER: Iwahashi J

PROVIDER: S-EPMC87992 | biostudies-literature | 2001 Apr

REPOSITORIES: biostudies-literature

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Isolation of amantadine-resistant influenza a viruses (H3N2) from patients following administration of amantadine in Japan.

Iwahashi J J Tsuji K K Ishibashi T T Kajiwara J J Imamura Y Y Mori R R Hara K K Kashiwagi T T Ohtsu Y Y Hamada N N Maeda H H Toyoda M M Toyoda T T

Journal of clinical microbiology 20010401 4

In Japan, the use of amantadine for treatment of influenza A virus infection was not accepted until November 1998, although it was widely used for treatment of Parkinsonism. Since then, we have monitored the emergence of amantadine-resistant viruses and isolated two viruses from patients on long-term treatment with amantadine. ...[more]

PMID: 11283109

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Project description:The emergence and widespread occurrence of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1 virus, are major concerns. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses, we performed full genome sequencing of prepandemic 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 2007-2008 and 2008-2009 influenza seasons were analyzed. Sequencing of the full genomes of these viruses was performed, and the phylogenetic relationships among the sequences of each individual genome segment 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 evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-2008 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 2008-2009 season and further acquired at least one mutation in each of the polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), hemagglutinin (HA), and neuraminidase (NA) genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages, followed by the H275Y substitution in the NA gene and other mutations elsewhere in the genome, contributed to the emergence of the oseltamivir-resistant lineage. In contrast, amantadine-resistant viruses from the 2007-2008 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.

Dataset Information

Isolation of amantadine-resistant influenza a viruses (H3N2) from patients following administration of amantadine in Japan.

Publications

Isolation of amantadine-resistant influenza a viruses (H3N2) from patients following administration of amantadine in Japan.

Similar Datasets

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