Tamura D, Mitamura K, Yamazaki M, Fujino M, Nirasa. Oseltamivir-Resistant Influenza A Viruses Circulating in Japan. J Clin Microbiol. 2009 Mar 4
Surveillance studies of influenza viruses circulating in Europe and other countries in 2007-2008 have revealed rates of resistance to oseltamivir of up to 67% among H1N1 viruses. Here, we examined 202 clinical samples obtained from patients infected with H1N1 virus in Japan in 2007-2008 for oseltamivir resistance and found that three were oseltamivir-resistant (1.5%). The IC50 values, as measured by a sialidase inhibition assay of these drug-resistant viruses, were >100-fold higher than those of the non-resistant viruses (a median of 12.6 nmol/L). The His274Tyr (N2 numbering) mutation of the neuraminidase protein, which is known to confer oseltamivir resistance, was detected in these three isolates. A phylogenetic analysis showed that one virus belonged to a lineage that is composed of drug-resistant viruses isolated in Europe and North America and that the other two viruses independently emerged in Japan. Continued surveillance studies are necessary to observe whether these viruses will persist.
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