Influenza At The Atomic Level

Since 2003, more than 300 people have been infected by the H5N1 influenza virus, which initially evolved in South Asian bird populations. Researchers have long wondered how the virus evolves from a pathogen that can infect birds to one that can infect humans and whether it could eventually evolve to be transmissible between humans. By solving X-ray crystal structures, a team of researchers led by microbiologist George F. Gao at the Chinese Academy of Sciences in Beijing took a first step toward answering these questions at an atomic level (Science, DOI: 10.1126/science.1236787). One structure is an H5N1 viral hemagglu­tinin protein complexed with avian α2,3-linked sialic acid receptors, the main route for infection. The other structure is a mutated H5N1 virus hemagglutinin that can bind human α2,6-linked sialic acid receptors found in the upper respiratory tract and red blood cells. The researchers discovered a fundamental difference in the binding of the viral proteins to the receptors. Binding of H5N1 hemagglutinin to bird receptors occurs when the sugars are in a trans conformation, whereas binding of mutated hemagglutinin to human receptors occurs when the sugars are in a cis conformation. The researchers hope the work will inform the development of therapeutics to prevent and treat the infection.