Recombinomics: Tamiflu Resistant H1N1 in Kenya Has A193T

Commentary

Tamiflu Resistant H1N1 in Kenya Has A193T
Recombinomics Commentary 14:20
February 5, 2009

HA sequences from Kenya have been released through the US Air Force surveillance program. These sequences identified high levels of oseltamivir resistance H1N1 in Kenya, and provided additional support for recombination and the role of A193T in the fixing of H274Y.

Most of the sequences fell into two groups. One matched the sequences released from isolates collected last season in Kenya. These sequences had G189N (H3 numbering), which was encoded by two adjacent non-synonymous changes, G604A and G605A. However, a second group matched the oseltamivir resistant isolates identified in South Africa over the summer. These isolates also had G189N, but were flanked by two additional changes S187N and A193T. S187N was found in clade 2C in Hong Kong, while A193T had also been in clade 2C prior to acquisition by the clade 2B sub-clade that emerged worldwide this season. There were six isolates (see list below) that had the three receptor binding changes, S187N, G189N, and A193T, which was the dominant sub-clade in South Africa and also was in an isolate from Washington state. Moreover, phylogenetic analysis of the NA sequences suggests an isolate from Chiba, Japan also matches this group. The isolates in Kenya were collected in October and November, but support an earlier Kenya origin for G189N.

In addition to the series that matches the isolates from South Africa, another isolate, A/Mbagathi/7586/2008, has G189A and A193T, which matches another isolate from the US that emerged this season, A/Hawaii/19/2008. This combination also matches another series from Japan this season, based on phylogenetc analysis of NA.

Another Kenya isolate from the summer, A/Kisumu/6543/2008, has G189N plus H196R. H196R is in the dominant H1N1 sub-clade reported to date in the United States, as well as multiple locations in Japan this season.

Yet another isolate, A/Kisii/7577/2008, has G189N plus A193T.

Thus, the isolates from Kenya contain a number of combinations of receptor binding domain polymorphisms which match H1N1 isolates with H274Y on NA, as well as A193T on HA.

S187N, G189N, A193T
Kisii/7541/2008
Kisii/7547/2008
Kisii/7559/2008
Kisii/7562/2008
Kisii/7570/2008
Kisii/7576/2008
Johannesburg/10/2008
Johannesburg/25/2008
Johannesburg/34/2008
Johannesburg/35/2008
Johannesburg/46/2008
Washington/05/2008
Chiba/86/2008

G189A, A193T
Mbagathi/7586/2008
Hawaii/19/2008
Miyagi/35/08
Yamaguchi/26/08
Yamaguchi/27/08
Yamaguchi/28/08

H196R (G189V, A193T also in all except Kisumu)
Kisumu/6543/2008
Hawaii/21/2008
Pennsylvania/08/2008
Pennsylvania/092008
Texas/15/2008
Texas/16/2008
Texas/17/2008
Texas/18/2008
Sendai/103/08
Sendai-H/2103/08
Sendai/104/08
Sendai/105/08
Yokohama/95/08
Yokohama/96/08

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