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Increased Discordance Between Human and Swine H3N2v
Recombinomics Commentary 01:15
October 9, 2012

The USDA has released an series of 2012 H3N2v swine sequences, which includes 15 matches with recent H3N2v human cases.  Although all released human sequences from 2011 and 2012 cases have an H1N1pdm09 M gene, the first 10 cases from 2011 have an N2 lineage that traces back to H1N2v swine.  In contrast, the last 2 cases in 2011 and 89/91 human H3N2v sequences from 2012 have an easily distinguished N2, which is from an H3N2v swine lineage.  The dramatic switch in the N2 lineage in the human cases was not seen in the swine H3N2v, especially those identified by the USDA through their voluntary swine surveillance program.

This discordance has been noted previously, but was increased by the 16 sets of 2012 H3N2v sequences, all of which matched the 2011 human H3N2v cases.  Five of the sets of HA, NA, MP sequences were from isolates discussed previously when the USDA released sequences for the five internal genes.  The five isolates (A/swine/Illinois/A01241469/2012, A/swine/Illinois/A01241840/2012, A/swine/Illinois/A01241842/2012, A/swine/Illinois/A01241871/2012, A/swine/Illinois/A01241916/2012) had internal gene sequences that were closely related to swine matches with the human cases from 2011, and the recently released sequences had an H1N1pdm09 M gene as well as HA and NA genes which matched the human isolates, which was also true of the 12 additional sets of sequences (see list below).  Although most of the new sequences were also from Illinois, the were collected throughout the first five months of 2012, which extended time frame for at least one Illinois H3N2v match to 8 months (at least one Illinois swine sequence was identified for each of the last 3 months of 2011).

In spite of the detection of this sub-clade in Illinois swine, as well as other states, including Ohio and Indiana, only two of the recent human cases match the N2 lineage in these swine isolates (and the two human cases from Michigan also had a PB1 sequence with E618D, as did recent Ohio swine).  The other 88 sets of sequences from July / August human cases matched the lineage with an N2 from H3N2v swine, which was first reported in human cases at the end of 2011 (from a day car center in Mineral County, West Virginia).

This large discordance between human and swine H3N2v lineages suggest the lineage in most 2012 human cases is evolving in humans, and is rarely found in swine not at agricultural fair venues, although the recent swine cases identified in Indiana and Ohio may signal an entry into the swine population which increase frequencies in subsequent USDA samples acquired through its voluntary surveillance system.

The discordance also raises concerns that the CDC focus on agricultural fairs during the influenza off season is creating a serious undercount in H3N2v cases infected via human to human transmission.

Name                                                                Collection
A/swine/Iowa/A01202529/2011                    8/22/11
A/swine/Iowa/A01202530/2011                    8/22/11
A/swine/Iowa/A01202573/2011                    9/07/11
A/swine/NY/A01104005/2011                       9/13/11 
A/swine/Iowa/A01202878/2011                    9/17/11
A/swine/Iowa/A01202879/2011                    9/17/11
A/swine/Indiana/A01202621/2011               9/28/11
A/swine/Iowa/A01202639/2011                    9/30/11
A/swine/Iowa/A01202640/2011                    9/30/11
A/swine/Illinois/A00857138a/2011             10/20/11 
A/swine/Illinois/A00857138b/2011             10/20/11
A/swine/Illinois/A00857300/2011               11/28/11 
A/swine/Illinois/A01202978/2011               12/16/11
A/swine/Illinois/A01240835/2012                 1/03/12
A/swine/Illinois/A01240836/2012                 1/03/12
A/swine/Illinois/A01240908/2012                 1/03/12
A/swine/Illinois/A00857304a/2012               1/05/12  
A/swine/Illinois/A00857304b/2012               1/05/12
A/swine/Ohio/A01203186/2012                    1/24/12
A/swine/Indiana/A01327213/2012                2/06/12
A/swine/Indiana/A01327215/2012                2/06/12
A/swine/Illinois/A01241469/2012                  2/08/12
A/swine/North Carolina/A01203272/2012+  2/13/12
A/swine/Illinois/A00857318a/2012*               2/23/12
A/swine/Texas/A01104013/2012                   2/15/12
A/swine/Illinois/A01241840/2012                   2/27/12 
A/swine/Illinois/A01241842/2012                   2/27/12 
A/swine/Illinois/A01241871/2012                   2/29/12 
A/swine/Illinois/A01241876/2012                   2/29/12 
A/swine/Illinois/A01241916/2012                   3/01/12
A/swine/Illinois/A01327184/2012                   3/15/12
A/swine/Indiana/A01203372/2012                 4/03/12
A/swine/Illinois/A01327629/2012                   4/15/12
A/swine/Illinois/A01327903/2012                   5/08/12 
A/swine/Illinois/A01327905/2012                   5/08/12 
A/swine/Iowa/A01203503/2012                      5/09/12
A/swine/Indiana/A01203509/2012+               5/09/12
A/swine/Indiana/A01203521/2012                 5/15/12
A/swine/Indiana/A01203522/2012                 5/15/12
A/swine/Ohio/1/2012#                                           6/12
A/swine/Ohio/6/2012#                                           6/12
A/swine/Ohio/7/2012#                                           6/12
A/swine/Ohio/9/2012                                             6/12
A/swine/Indiana/A00968380/2012+               7/18/12
A/swine/North Carolina/A1300820/2012       7/19/12
A/swine/Iowa/A01243736/2012                      7/25/12 

+ = 2011 WV lineage
* = H1N1pdm09 NP
# = E618D PB1
bolded date = newly confirmed match

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