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With the holiday season fast approaching, that can only mean one thing: flu is on the way and if the scaremongers are to be believed the long-forewarned bird flu epidemic might follow in its wake any time soon. Tim Cross, Jun Hu, Riqiang Fu, Katsuyuki Nishimura, Li Zhang, and Huan-Xiang Zhou of Florida State University and colleagues David Busath and Viksita Vijayvergiya at Brigham Young University have exploited the 15-ton 900 MHz NMR machine at FSU to help them figure out the mechanics of infection by influenza A virus. The common human form of the disease already kills several hundred thousand people every year, and forecasters predict the emergence of a human transmissible form of avian influenza could kill millions more. Cross, who is director of the FSU lab's Nuclear Magnetic Resonance (NMR) program and his co-workers have obtained detailed pictures of the viral coat. "Using NMR helps us build a blueprint for a virus's mechanics of survival," explains Cross, "The more detailed the blueprint, the better our chances of developing drugs capable of destroying it." The researchers have found that the virus' protein coat contains channels that control various biochemical reactions crucial to viral infection and replication. The tetrameric M2 protein has four key histidine residues within this viral pore that are known to be involved in proton selectivity of the channel, pH activation, gating, inhibition, and the specific conductance mechanism. Conduction of protons into the viral core of influenza A once the virus is inside a cell causes the viral coat to be stripped off and genetic material to be released. Solid state NMR of the M2 protein channel within a hydrated lipid bilayer has allowed the team to uncover the details of this mechanism. They have found that protonation of the third of the imidazole rings of the histidine residues causes acid activation of the channel, which changes the distribution of electric charge within the channel and allows protons to pass through uninhibited. "This is a viral structure we haven't seen before," Busath explains, "And yet, through these tiny little doors, acids must come in and DNA must go out if the virus is to survive." He adds that blocking these channels would terminate normal viral functions and stop infection in its tracks. The next step will be to discover what structural properties endow these protein channels with their specificity and so provide new targets for antiviral drug design. Related links: The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd. |
.jpg)  Cross (top) and Busath waging a "holy" war against the influenza virus (below) |
