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Commentary

Emergence of H1N1 Relenza Resistance In Pennsylvania
Recombinomics Commentary 14:48
July 17, 2008

The recent explosion of H1N1 Tamiflu (oseltamivir) resistance worldwide has focused attention on the other neuraminidase inhibitor, Relenza (zanamivir).  Recently deposited H1N1 sequences from Asia had a novel polymorphism, Q137K, which confer resistance to Relenza (see list below).

A recently released NA sequences from Pennsylvania, A/Pennsylvania/01/2008, contains a mixture which encodes for both Q136 and Q136K.  Like the more recent isolates from Asia, this isolate is on a clade 2B (Brisbane) background.  In contrast, the earlier isolates were on a clade 2A (Solomon Islands) background. 

Moreover, the introductions onto each background were independent suggesting that the Q136K polymorphism is spreading among H1N1 backgrounds by the same mechanism that is spreading the Tamiflu resistance H274Y onto multiple genetic backgrounds.

Like the spread of G743A on clade 2.2 backgrounds, this sudden and concurrent spread of the same polymorphism onto multiple genetic backgrounds is most easily explained by homologous recombination.

Clade 2B (Brisbane)
A/Thailand/39/2008
A/Christchurch/62/2007
A/Brisbane/308/2007
A/Brisbane/334/2007

Clade 2A (Solomon Island)
A/Philippines/905/2006
A/Philippines/604/2006
A/Philippines/1279/2006
A/Brisbane/297/2006

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