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Commentary
Novel H1N1 With D225N Raises Pandemic Concerns
Recombinomics
Commentary 13:05
April 7, 2011
Of greatest concern was the presence of D225N in the H1N1 sequence from the fatal case (36M), A/Mexico/InDRE1945/2011, from the traffic department. The index case for the cluster was the partner of the above case and was diagnosed as a fatal atypical pneumonia. The failure to identify influenza A or H1N1 increased concerns that the sub-clade was generating false negatives. Reports indicate at least one additional co-worker was in critical condition, signaling transmission of a deadly sub-clade. This was supported by the presence of D225N in the sample which was from the upper respiratory tract (nasopharyngeal swab).
The other two HA sequences (A/Mexico/InDRE1946/2011 and A/Mexico/InDRE1947/2011) lacked D225N, but were otherwise identical to the above sequence at the protein level. The sequence had A189T, a receptor binding domain change that may be linked to immunological escape. Similar changes were seen in the 2008 seasonal H1N1 sequences evolving away from the immunological response to Brisbane/59/2007, which raises concerns that the aggressive vaccine campaign initiated in Mexico and Venezuela will have limited effect. The current H1N1 target is California/7/2009, and a number of studies indicated the current H1N1 has evolved away from that sequence.
Anecdotal reports cite additional examples of D225N in severe and fatal cases, raising concerns that this sub-clade transmits. The emergence of the current H3N2 sub-clade involved the acquisition of two similar changes, S189F and D225N. Thus, D225N on the appropriate influenza genetic background readily transmits in humans, and the novel sub-clade in Chihuahua has A189T coupled withD225N in the fatal case.
The 2011 H1N1 from the United States has been withheld by the CDC. A small series released by the Air Force indicated the novel sub-clade was widespread in the United States, although the 2011 sequences lacked D225N. However, a closely related 2010 sequence from Pennsylvania, A/Pennsylvania/07/2010, had D225G, which has been linked to severe and fatal H1N1 cases.
Release of 2011 H1N1 sequences from the United States, including Texas and New Mexico, is long overdue.
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