Scientists Identify Achilles' Heel of Flu Viruses
Scientists have recently identified a family of human antibodies that can take out an unprecedented number of different types of flu viruses, including H5N1 'bird flu' and the 1918 H1N1 'Spanish flu', which killed millions around the world during World War I, as well as seasonal flu. Using SSRL's Beam Line 9-2, Dr. Robert Liddington from the Burnham Institute for Medical Research led a team of scientists that determined the crystal structure of one such antibody, F10, in complex with the hemagglutinin H5 to unveil the molecular mechanism of virus neutralization. Results were published online 22 February 2009 in the journal Nature Structural and Molecular Biology.
Seasonal influenza kills more than 250,000 people worldwide each year. A pandemic influenza, such as the highly pathogenic avian influenza (HPAI) H5N1, poses a grave threat to society. Each seasonal flu vaccine contains three influenza viruses: one A (H3N2) virus, one A (H1N1) virus, and one B virus. The viruses in the vaccine change each year based on international surveillance and scientists' estimations about which types and strains of viruses will circulate in a given year. However, flu vaccines are not always effective - due in part to the rapid change of the globular head of hemagglutinin (HA or H), the major antigen on the surface of flu virus.
Using x-ray crystallography, the team solved the crystal structure of a potent antibody F10 in complex with hemagglutinin H5. The heavy chain of F10 binds to a highly conserved pocket, near the fusion peptide, in the stem of hemagglutinin. Binding of antibody F10 disables HA's ability to induce fusion between the viral membrane and the host cell membrane, a critical step in influenza virus infection. The F10 epitope is common among many different types of flu viruses, which explains its broad spectrum of neutralization against many different types of flu viruses.
Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, Santelli E, Stec B, Cadwell G, Ali M, Wan H, Murakami A, Yammanuru A, Han T, Cox NJ, Bankston LA, Donis RO, Liddington RC, Marasco WA. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat. Struct. Mol. Biol. 16, 265 - 273 (2009).