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Novel Chihuahua H1N1 Sub-clade In Pennsylvania With D225G

Recombinomics Commentary 20:50
April 5, 2011

The recently released sequences from Chihuahua, Mexico have raised concerns that the re-emerging sub-clade would rapidly spread and cause more severe disease.  The sub-clade has one receptor binding domain (RBD) change, A189T, as well as three additional non-synonymous changes (N34D, S165N, and V275I). 

The concerns were increased by the presence of D225N in the sequence,
A/Mexico/InDRE1945/2011, from a fatal case (36M).  This case was part of a cluster in the traffic department in Juarez.  The partner of the above case also died, and a third co-worker was in critical condition, raising concerns that the D225N was linked to this cluster and c`ause the severe and fatal cases.

The above sub-clade was seen in a small number of human cases in the US in the spring of 2010.  However, in addition to the spring cases, one isolate from August, A/Pennsylvania/07/2010, was more closely related to the Chihuahua sub-clade.  The clinical status of the case (23F) was not known, but the sequence has D225G.  Previously, sequences from autopsy lung samples collected in Ukraine in 2009 had a high frequency of D225G and D225N, raising concerns that the emergence of a sub-clade with a high frequency of isolates with these changes would lead to an increase in severe and fatal case.

Moreover, these changes may lead to immunological escape which would drive the spread of this sub-clade.

The current extent of spread in the US is not known.  Recently the Air Force released 2011 H1N1 sequences from military personnel and dependents.  This sub-clade was present in cases found throughout the US (NJ, NC, SC, FL, AZ).  However, sequences from Texas were not released by the Air Force, and the CDC has withheld the release of 2011 isolates from patients throughout the US.  Epimiological data links the outbreak in Chihuahua with travel from New Mexico and Texas.

The sub-clades with A189T and an additional change at position 225 (D225G or D225N) have parallels with the emergence of H3N2 with adamantine resistance.  The H3N2 sub-clade was characterized by S193F and D225G.  Moreover, the co-circulation of the S188T and A189T sub-clades could lead to sequences with both RBD changes, which have been seen in recent sequences from North Carolina (A/North Carolina/AF21793/2010) and the country of Georgia (A/Georgia/51/2011).

Therefore release of 2011 sequences from severe and fatal cases in the United States, as well as Mexico and Venezuela is overdue.

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