Natural Recombination and Reassortment in Korean Swine
Recombinomics Commentary
March 3, 2005
>> Each of the strains were genetically manipulated and contained genetic bits of an avian virus unlike those now prompting separate bird flu concerns. <<
The sequences in swine in Korea did not have evidence of genetic manipulation. The isolates have various combinations of human WSN/33 and Korean avian H9N2 sequences, which happens via reassortment. Two of the genes had examples of recombination, but these are also natural viral evolution.
WSN/33 has a number of characteristics that makes it particularly virulent. It is missing a glycosylation site on NA, which allows it to sequester plasminogen. This in turn facilitates cleavage of the HA precursor, which is required for viral entry. This property generates a broad tissue tropism allowing the virus to grow in mouse brains and be quite lethal.
WSN/33 also has a mutation at position 31 in the M2 gene which makes it resistant to Amantadine and Rimantadine. However, resistance at this position has been seen in other human isolates, as well as H5N1 isolates from Vietnam and Thailand.
The 1933 origin of the virus poses as hazard to people born after 1933 due to natural changes. Two of the swine isolates are H1N1, and there have been many changes in both genes since 1933. Comparison with the 1999 H1N1 used in the current trivalent human vaccine reveals 60 amino acid differences in HA and 45 in NA.
In contrast, the number of differences in HA between A/Wyoming/3/2003, and either A/Wellington1/2004 or A/California/7/2004, is only 6-9 changes. These much smaller differences produce reduced titers in cross reacting antisera.
One of the virulence factors in WSN/33 is missing from the swine isolates. WSN/33 has a mutation at position 627 in the PB2 protein, but only two of the Korean swine isolates have WSN/33 sequences in PB2, but both are recombinants and have only the 5' portion of the WSN/33 gene. The avian 5' half has a wild-type sequence coding for position 627.
Thus, while it would be unlikely that a civilian lab would deliberately mix avian and WSN/33 sequences in the same cell, the WSN/33 virus may have been used in error, or the mixing with H9N2 Korean avian sequences could have happened in the swine via a dual infection in vivo.
However, how the virus moved from a lab to swine on farms in Korea, remains unexplained.
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