Wang%20and%20Palese%20NandV

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NATURE STRUCTURAL & MOLECULAR BIOLOGY VOLUME 16 NUMBER 3 MARCH 2009 233 mutations in the antigenic sites easily avoid neutralization by existing host antibodies, leading to seasonal influenza outbreaks. The emergence of antigenic variants also dictates the frequent production of new vaccines containing relevant virus strains. Sui et al. demonstrate that a region in the stem of the hemagglutinin molecule containing the fusion peptide is structurally conserved across multiple viral subtypes. They isolated a panel of single-chain Fv (scFv) antibodies against this region that show an unprecedented degree of cross- reactivity. a small subset of which confer protective immunity. Most virus-neutralizing antibodies (nAbs) bind the hemagglutinin molecule, one of three proteins on the viral envelope ( Fig. 1 ). Anti-hemagglutinin nAbs work either by blocking attachment of virus to the host cell or by disrupting fusion of hemagglutinin with the endosome, preventing release of viral RNA into the cytoplasm 2,3 ( Fig. 2 ). Most nAbs bind specific antigenic sites surrounding the receptor binding pocket of hemagglutinin, preventing viral attachment to the host cell ( Fig. 1b ). Escape variants with Influenza viruses remain a significant cause of morbidity and mortality worldwide. Circulating virus strains demonstrate a dramatic increase in resistance to available drugs, making the development of new treatments, both prophylactic and therapeutic, a priority. The influenza vaccine is by far the most effective means of preventing infection, but current vaccines leave room for improvement as they require near-annual reformulation and accurate prediction of circulating strains for the upcoming season. A universal influenza virus vaccine would represent a tremendous medical advancement; however, owing to the remarkable ability of the virus to tolerate changes in antigenic structure, a ‘one shot’ vaccine remains theoretical. The search for a common surface epitope between strains that elicits a neutralizing immune response has turned up little of promise; antibodies in the literature that protect against multiple strains of influenza remain extremely rare. An elegant study by Sui and colleagues now demonstrates that a universal immune- based treatment or vaccine may not be out of reach. They show that specific antibodies that prevent viral fusion with the host cell are able to neutralize across hemagglutinin subtypes including both avian H5 viruses
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This note was uploaded on 01/02/2010 for the course BIBC BIBC 100 taught by Professor Buehler during the Fall '09 term at UCSD.

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