Tracing WSN/33 Human Bird Flu Squences in Swine in Korea
Recombinomics Commentary
February 7, 2005
Sequences of the WSN/33 PA gene from defective interfering (DI) RNA has been made available at GenBank. These four sequences, are 400 (D10574), 432 (D10573), 462 (D12779), 560 (D12778) bp in length and are being studied for their ability to interfere with WSN/33 replication. WSN/33 is a popular H1N1 lab strain of influenza that was isolated from mouse brains in 1940. It grows well in tissue culture and is used in a variety of lab experiments, including those that study the lethality of genes from the 1918 pandemic strain. WSN/33 is a dangerous strain because it is derived from a 1933 isolate, the first human flu virus ever isolated in a lab, and it is missing a glycosylation site that allows it to sequester plamsminogen, resulting in a broad host range and neurotropism.
The virus has managed to move from a secured lab environment to infect swine on farms in Korea. This has presented a significant health risk because the virus has become widespread and has both reassorted and recombined with Korean avian (H9N2) genes. Six of the sequences became publicly available at the end of November, 2004 although the health risk posed by these isolates has not been addressed publicly by the WHO.
In addition to the health concerns, the mystery on how the virus moved from a lab to many pigs on various farms in Korea has not been addressed. The virus is not grown in the Korean lab that sequences the swine isolates, and each of the 6 isolates on deposit is different in composition and/or sequence. Two of the isolates are H1N1 and 4 are H9N2. The gene sequences differ slightly between isolates as do the number of human genes (which range from 3-7). The gene sequence differences (polymorphisms) however can be used to trace the origin of the WSN/33 sequences. There are several polymorphisms found in all of the WSN/33 swine sequences that differ from the WSN/33 sequences from the lab strain. One difference was in the PA gene. All of the swine isolates are G1990A, while the WSN/33 sequence is the 1990G wild type.
The change to A had been observed in another DI isolate from England in the mid 90's. However, it was unclear if this difference was stable or if the wild type sequences were unstable since it was only in the one isolate. However, the four sequences placed on deposit all have the wild type sequence, indicating that the G1990A can serve as a marker to trace the WSN/33 sequences in swine. Although there is a match for the DI in England, that isolate had 3 other DI genes which had polymorphisms that did not match the swine WSN/33 sequences. However, there are a number of informative markers of various genes in the swine sequences, so additional sequencing of lab isolates of WSN/33 should be able to pinpoint the origin of the WSN/33 sequences in swine.
The WSN/33 could have infected the pigs (or birds which then infected the pigs) via a civilian lab accident. Alternatively, these sequences could represent a military experiment that resulted in an unplanned release. Moreover, at this point bioterrorism cannot be ruled out.
However, since at least six WSN/33 related sequences from swine are already publicly available and these isolates contain informative markers, an aggressive investigation should be able to determine the source of the WSN/33 sequences in swine in Korea.