Recombinomics: South African H1N1 Tamiflu Resistance in the United States

Commentary

South African H1N1 Tamiflu Resistance in the United States
Recombinomics Commentary 14:39
December 17, 2008

The United States CDC has released HA H1N1 sequences from isolates collected over the summer and the beginning of this season. In week 43 the CDC characterized the first H1N1 isolate for antiviral resistance. It was oseltamivir sensitive but amantadine resistance, which was the pattern for all clade IIC (Hong Kong) isolates reported last season. That isolate appears to be A/California.07/2008, which matched the resistance pattern above and phylogenetic analysis clearly demonstrated it was clade IIC and closely related to clade IIC isolates collected in the US last season. The isolate was collected September 4, 2008.

All 44 H1N1 isolates tested after the IIC isolate above appear to be clade IIB (Brisbane) because all are oseltamivir resistant and amantadine sensitive. This high level of resistance was seen over the summer in South Africa, where reports on the first 225 H1N1 isolates tested were oseltamivir resistance.

Several months ago 8 HA sequences and 8 NA sequences from South Africa have also been released at Genbank. All sequences evolved from the IIB sub-clade that was dominant in several countries in Europe, including Norway, where H274Y frequencies exceeded 65%. This dominant sub-clade also had D354G, which had been present previously in clade IIA and IIC. The acquisition by IIB appeared to offer a selective advantage because all NA sequences in South Africa had this change.

In addition, the dominant HA sequence from South Africa had a cluster of changes near the receptor binding domain positive 190 (H3 numbering). These five changes were found in a variety of H1N1 isolates. Two were present in H1N1 isolates from Kenya, two were in H1N1 isolates from the 1940’s, and one was in clade IIC in Hong Kong, suggesting acquisitions linked to a series of recombination events.

This cluster of changes is present in the HA isolate collected over the summer in Washington, A/Washington/05/2008, demonstrating the movement of these changes from South Africa to the northern hemisphere and increasing the likelihood that this rapid evolution will be present in the H1N1 isolates in the United States this season, which has created a mismatch between antiviral recommendations and resistance in circulation in the United States this season..

Four of these five changes also produce 3 non-synonymous changes, which may decrease the effectiveness of the current H1N1 vaccine, which targets the Brisbane clade IIB target, but the isolate used did not have the recent changes.

Release of additional HA and NA sequences from this season would be useful. It is likely that the 100% levels of resistance in clade IIB in the United States will continue, and the level of the South Africa sub-clade would be of interest.

Media Links