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H1N1 RBD D225G and D225N in Mexican Swine
Recombinomics Commentary 19:54
December 24, 2009

Sequences from an April outbreak of H1N1 in Queretaro, Mexico were released at Genbank.  The HA sequence, A/swine/4/Mexico/2009, had mixed signals at three positions within the receptor bind domain, coding for wild type as well as D225G, D225N, and Q226R.  The "immediate notification" of was sent to OIE on December 12.

This April outbreak started a few weeks after a swine outbreak in Alberta, Canada and both remain candidates for pandemic H1N1 circulation in swine independent of human to swine transmission.  The Alberta outbreak was initially said to be due to infection by a worker returning from Mexico, but the worker tested negative for H1N1 and multiple sequences from the herd were heterogeneous, indicating the infections were not due to a single recent introduction.  Thus, the close relationship between the swine sequences and pandemic H1N1 suggested that the swine isolates may have been representative of pandemic H1N1 circulating in swine prior to the jump to humans.

The sequences in Mexican swine also are candidate sequences.  In addition to the changes within the receptor binding domain, the HA sequence has a number of additional polymorphisms frequently found in swine.  Like the outbreak in Alberta, no matching sequence from a human linked to the herd has been presented.  However, the mixed signals coding for D225N and Q226R were present in human spring isolates, including California/7/2009, which is the target for the current vaccine.

However, there have only been three reported human cases with both D225G and D225N.  All three were fatal and all involved the same mixed signals reported for the swine sequence.  One sequence was from a case (28F) in Utah (A/Utah/42/2009) who died Jul 24, while the other two from Mexico were just released at Genbank.  One patient (25M) had samples collected Oct 31, A/Mexico/InDRE50625/2009, while the other (40M) had samples collected Nov 1, A/Mexico/InDRE50617/2009. The fact that both sequences were from the adjacent province of San Luis Potosi may signal human to human transmission.

The association of the D225G and D225N combination with fatal cases reduces the likelihood that the swine outbreak in Queretaro, Mexico was cause by human to swine transmission.  However, these sequences do raise concerns of swine acting as reservoir for such changes.  D225G is common in swine and the number of swine outbreaks continues to rise worldwide.  Both Russia and South Korea have filed immediate OIE reports this week, and the report from South Korea is on 15 outbreaks throughout the country.  Similarly, the number of reports of H1N1 in other species continues to grow almost daily.  This week the detection of H1N1 in a dog in New York confirms canine cases in China, and there have been multiple reports on domestic cats and ferrets, which in association with multiple reports of H1N1 in turkeys, suggest the number of H1N1 infected species is large and growing.

More intense surveillance of these reservoirs and release of swine H1N1 sequences from the Mexico repository would be useful.

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