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Pandemic Influenza as a Bioweapon

Recombinomics Commentary
February 23, 2005

>>  "Anyone who is honest about this has to admit that if al Qaeda launches a spectacular biological attack which could cause contagious disease to be spread, no entity in the world is prepared for it," Noble said.  "Not the U.S., not Europe, not Asia, not Africa." <<

Since the WSN/33 situation in Korea provides some valuable insight into detection and reporting of bird or human flu, and wire services are carrying stories about biologic attacks by terrorists causing a contagious disease, it is worth reviewing some of the lessons learned from the swine WSN/33 infections. 

If pandemic flu is the contagious disease of choice, selection of WSN/33 at this time would offer some advantages.  It is already transmissible from human-to-human, has been shown to be lethal in mice, has mutations in NA and PB2 that increase lethality, is widely available, and could be used without genetic manipulation.

As has been seen in Korea, introduction of the agent into pigs would allow it to spread almost undetected.  Verification of its spread (or existence) has proven to be exceedingly difficult.  Movement from swine to humans has not been reported and all reported isolates are missing the PB2 mutation.  This may be due to a survival selection offered by recombining or reassorting with prevalent H9N2 subtypes.  Most of the swine isolates have an avian PB2, but even the isolates that have half of a human PB2 have the 3' half of the human gene replaced with avian sequences.  Thus, the results from the Korean swine may indicate that starting with a very lethal virus has disadvantages in that a less lethal virus will emerge virtually undetected.

A second choice would be the H5N1 currently causing the high case fatality rate in Vietnam, Thailand, and Cambodia.  This version would be even more available, since it is excreted in large amounts by asymptomatic ducks, and is present in multiple organs in fatal infections.  Although human-to-human transmission of H5N1 is limited, infecting a few international travelers would generate worldwide panic if these passengers became ill outside of areas with indigenous H5N1.  Use of infected currency as a vector for transmission has been widely discussed.

A third approach would involve genetic manipulation.  Creating an efficiently transmitted H5N1 would be relatively easy.  Swapping a human receptor binding domain from a human flu virus into an H5 backbone would improve transmission efficiency and such an agent would quickly disseminate worldwide.  Of course such an agent would be hard to control, and most unvaccinated people would be at risk.  Since influenza evolves via recombination, implementation of an efficient laboratiry strain might be eclipsed by a natural version, and there would be uncertainty over the origins of such an agent.

Thus, like WSN/33 in Korean swine, taking credit for such a biologic attack may be difficult, since most countries appear to be unable to even determine if such an attack has happened.

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