CONTROVERSIAL BIRD FLU VIRUS STUDY PUBLISHED: The first of two highly debated studies, revealing mutations that could make bird flu pandemic in humans, was just openly published amid fears of spawning bioterrorism.
• Here are the facts: H5N1 bird flu virus has circulated in poultry for more than 16 years, only rarely infecting humans. But humans lack immunity to H5N1 and infections are unusually severe, raising fears of a pandemic.
• Why is this work necessary and important? We don’t know if airborne H5N1 can be transmitted between humans. We don’t know what mutations may arise in the rapidly evolving virus that could make it transmissible. If we knew this, we could (1) monitor circulating or newly emerging variants for their pandemic potential, (2) focus eradication efforts on viruses that already have acquired subsets of molecular changes critical for transmission in mammals, and (3) stockpile antiviral compounds in regions where such viruses circulate, and initiate vaccine generation and large-scale production before a pandemic.
• How was this study done? The research focused on the viral hemagglutininprotein, HA, because it has a major role in determining host range of influenza A viruses. (For example, HA variants from human isolates prefer to bind to sialic acid coats of human cells whereas avian versions will bind well to avian cells). The researchers used a human virus with the avian HA and generated 2million random mutations. They infected ferrets, which are a good model for virology. The best adapted mutants spread to a nearby cage and infected healthy ferrets (none died).
• What did they find? The HA protein has a round “head” sitting atop a long “tail” (right image). The mutations shown in red help the viral protein bind the human receptor better (a fragment is shown in orange). The surprise was a 4th mutation in the tail that helps the viral protein do a better job in fusing the virus with the human cell membrane.
• What next? So the proverbial cat’s out of the bag. Not so much brouhaha this time around. Since the study was done in ferrets, it’s not known whether they would transmit as well in humans, and how harmful they would be.
Open Access Original Paper: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10831.html
Also, Tommy Leung ‘s ScienceSunday post: http://goo.gl/kPFVK