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Commentary
Emergence
of Extensive Drug Resistant XDR-pH1N1 NOT
Recombinomics
Commentary 13:44
August 26, 2010
On August 26 the CDC notified Recombinomics that the GISAID entry on antiviral resistance is in ERROR. A/Kansas/05/2010 is SENSITIVE to oseltamivir and Zanamivir.
Yesterday the US CDC released two pandemic H1N1 sequences. Both were partial NA sequences (1386 BP) from original samples. One of the sequences, A/Kansas/05/2010, was tested for antiviral activity for oseltamivir (Tamiflu) and zamanivir (Relenza) and was resistant to both, representing the first pandemic influenza sequence reported to show resistance to Relenza, and the first sequence resistant to both FDA approved neuraminidase inhibitors. The NA sequence did not have H274Y, but did have two rare polymorphisms, S363N and I466M. The other sequence, A/Connecticut/23/2009, also had I466M, but antiviral resistance was not reported.Relenza resistance has been previously reported in seasonal H1N1, but the responsible polymorphism, Q136K, was only detected in virus in culture. Sequencing of original samples failed to detect Q136K, suggesting it was either generated during viral isolation, or was at levels below detection in the original sample.
In contrast, I466M was in both original pandemic H1N1 samples and was also in an earlier isolate from Poland, A/Poland/37/2009, as well as a swine H1N1 isolate, A/swine/Germany-SN/siv-leipz6340/09. In addition to I466M, another change at the same position, I466V, has been reported in A/Guam/NHRC0023/2009 and A/Bayern/73/2009, as well as swine isolates, A/swine/Germany-NW/IDT2884/04 and A/swine/Greven/IDT2889/2004.
These changes at NA position 466 (467 in N1 numbering) raise concerns that XDR (eXtensive Drug Resistant) strains of H1N1 are emerging in human pandemic as well as swine sequences.
More information on the quantitative aspects of the resistance is useful, as well as the resistance results for A/Connecticut/23/2009.
Additional NA sequences from isolates represented in Genbank and GISAID databases, as well as HA and MP sequences from the above isolates from Kansas and Connecticut would also be useful.
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