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CDC Calls Novel Human Triple Reassortants Variants
Recombinomics Commentary 15:00
December 26, 2011

Novel influenza A viruses that normally circulate in animals may infect humans. Following discussion among international human and animal health agencies, these viruses will now be referred to as “variant influenza viruses” and, as an abbreviation going forward, will be designated with a “v”; recent examples include A(H3N2)v, A(H1N1)v, and A(H1N2)v. In the second half of 2011, a number of U.S. residents were found to be infected with influenza A variant viruses, especially A(H3N2)v. Investigations have revealed human infections with these viruses following contact with swine as well as limited human-to-human transmission. While this virus has been detected in U.S. swine, it's unknown how widespread it is.

The above comments are from a new CDC webpage on variant viruses (triple reassortants).  These viruses were typically designated with a tr prefix, in accordance with their origin in swine in the 1990’s.  The initial double reassortants involved a dual infection with classical swine H1N1 and seasonal H3N2 from the early to mid 1990’s which gave rise to a reassortant with three human gene segments (PB1, H3, N2).  That was followed by an avian infection in the late 1990’s to swap out the other two swine polymerase geens (PB2 and PA) for avian flu genes to create a triple reassortant.  The external genes (H and N) were swapped with a variety of human and swine sequences, to create various triple reassortant serotypes such as trH1N1, trH1N2, and trH3N2 as being the most common.  Because of the history of these triple reassortants, the tr prefix implies the above historical events in swine.

Therefore, the CDC’s use of S-O (swine origin) in addition to the tr prefix, was just a propaganda ploy to bolster its swine origin narrative for the recent trH3N2 human cases (H3N2v).  The above comments confirm that the CDC is abandoning the S-O designations, and switching from the tr prefix to the v suffix, in preparation of pandemic declarations, which begin with the serotype and then and pdm for pandemic, followed by the year.  Thus, the novel trH1N1 that led to the 2009 pandemic is now called H1N1pdm09 and the trH3N2 (H3N2v) pandemic will be called H3N2pdm11 (although the limited testing and confirmation of sustained transmission may lead to an inaccurate H3N2pdm12 designation, which ignores the sustained transmission in 2011).

However, the dominant human H3N2v is less clear after the West Virginia cluster.  The first 10 human cases in 2011 had the same gene constellation which is generated as a reassortant between the dominant human H3N2v constellation in 2011 (represented by A/Pennsylvania/40/2010 or A/Wisconsin/12/2010), which contributed PA, PB2, HA, NP, NS) and a swine H1N2 (represented by
A/swine/Ohio/FAH10-1/2010), which contributed PB1, NA, and the H1N1pdm09 MP.  However, the two sequences from the Mineral County cluster (A/West Virginia/06/2011 and A/West Virginia/07/2011) have a different N2 (from swine H3n2), and that cluster represents the most sustained transmission (almost a month within the daycare center), without any swine exposure by confirmed or suspect cases, so both constellations may become common, especially in cases under the age of 10.

In addition to the twelve H3N2v cases in 2011, there are also H1 cases (H1N2v represented by A/Minnesota/19/2011, and H1N1v represented by A/Wisconsin/28/2011).  The H1N2v case had no swine exposure and was linked to an earlier symptomatic, but untested case, while the  H1N1v case had exposure that was occupationally linked.  However, the nature of the exposure including the status of the swine, remains unclear, as do the detection signals.  The H1N1v sequence also has an H1N1pdm09 M gene as well as PA.  However, the H1 and N1 are North American swine and not closely related to H1N1pdm09, so detection by the H1 target appears to be unlikely.  Similarly, the NP matches the H3N2v cases, so it might be detectable by the CDC PCR kit.  However. Direct sequencing yielded partial sequences for four genes, suggesting the RNA level was low, and the case may have been influenza A positive, but unsubtypable, or may have been forwarded to the CDC because of symptoms coupled with swine exposure, so the role of the swine in the infection remains unclear.

In any event, the detection of three different serotypes (H3N2v, H1N2v, H1N1v) as well as two distinct constellations in the H3N2v cases in the absence of swine linkage, signals a complex pandemic, which requires serious surveillance and sequencing.

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