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1933 WSN/33 H1N1 and 1957 A/Japan H2N2 Flu Escape Dangers

Recombinomics Commentary

April 27, 2005

>> Last fall, Sang Heui Seo of Chungnam National University in Daejeon, Korea, deposited flu sequences in GenBank that suggested that Korean pigs carried WSN/33, a flu strain widely used in labs but not known to occur in nature. Several experts and WHO dismissed the findings as the result of lab contamination (Science, 4 March, p. 1392) <<

Since there has been no reasonable explanation for the WSN/33 sequences at Genbank, it is unlikely that this issue will just fade away.  The issue remains unresolved, yet the hazard posed by WSN/33 in swine in Korea is significantly greater than the mistaken mailing of 1957 A/Japan H2N2 in proficiency tests.  The H2N2 pandemic strain was isolated in Japan in 1957.  Since H2N2 was replaced by H3N2 in the 1968 pandemic, those born after 1968 would have limited immunity.   However, most who were at risk for H2N2 in 1957 were elderly, and most of that population is no longer alive.  The mailed samples were sent to pathology labs that have infection control procedures in place.  The samples had tracking numbers and required signed receipts.  Thus, it was relatively easy to track the samples and ensure that they were destroyed. The only known escape of H2N2 was into a clinical sample where it was quickly identified.  This identification led to the discovery of H2N2 in the proficiency kits.

In contrast, WSN/33 presents a much more difficult problem at almost all levels.  The virus itself was selected for its pathogenicity and neurotropism.  It contains a number of mutations that would cause problems for infection control.  Although it does not have polybasic amino acids at its HA cleavage site, it is missing a glycosylation site in NA and therefore can sequester plasminogen and efficiently infect a spectrum of tissue types, including neurological tissues.  The NA is also missing 16 amino acids, which may decrease susceptibility to the anti-viral Tamiflu.  It has a mutation at position 31 in the M2 protein, so it is also resistant to two other anti-viral drugs, Amantadine and Rimantadine.  It also has a mutation at position 627 in the PB2 gene, which is associated with increased virulence.  WSN/33 lethality in mice is similar to a construct containing six WSN/33 genes plus H and N genes from the 1918 pandemic strain.

In addition to a number of mutations in the virus itself, isolating the virus from pigs has proven to be problematic for several labs in the WHO network.  Animal quarantine in South Korea has been unable to verify the serological data showing that a significant percent of pigs in South Korea have been exposed to the virus.  Similarly, labs inside and outside South Korea have not been able to confirm the WSN/33 sequence.  However, the Sang Seo lab has been able to detect antibody and additional sequences containing WSN/33.  This indicates the scope and procedures of the WHO confirmatory tests are flawed, producing negative data which is being offered of proof of lab error in the generation of the positive data.  The data, when properly analyzed, appear quite real.  Thus, there has been no independent confirmation of the sequences, although they were deposited at GenBank over six months ago.

The inability to detect the virus creates additional problems for resolving the circumstances that led to the WSN/33 infection of increasing numbers of swine on farms in South Korea.  This reservoir of H1N1 virus containing WSN/33 sequences poses a problem for both the swine and well as humans.  Since the virus is a human virus from 1933, it should be readily transmissible in humans and those born after 1933 would have limited immunity.  Since the swine isolates also have H9N2 genes, the various isolates could become endemic to the bird population and spread worldwide via migratory birds.  As the virus continues to spread undetected, the potential for a bird flu pandemic increase.

WHO's announcement that they considered the matter of WSN/33 infections closed is cause for concern.  Reliance on negative data to support a hasty conclusion in December can cause serious delays in addressing the problem.  Like H5N1, WSN/33 does not read press releases. 

Elimination of WSN/33 by proclamation can be hazardous to the world's health.

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