An avian influenza H5N1 virus that binds to human-type receptor

Departments of Microbiology, Faculty of Medicine Siriraj Hospital, Faculty of Science, and Faculty of Tropical Medicine, Mahidol University; Bureau of Epidemiology and Department of Disease Control; Faculty of Science, Kasetsart University; Thailand; and College of Life and Health Sciences, Chubu University, Japan

^* To whom correspondence should be addressed. Email: sipaw{at}mahidol.ac.th.

	Abstract

Avian influenza viruses preferentially recognize sialosugar chains terminating in sialic acid-2,3-galactose (SA2,3Gal), whereas human influenza viruses preferentially recognize SA2,6Gal. A conversion to SA2,6Gal specificity is believed to be one of the changes required for the introduction of new hemagglutinin (HA) subtypes to human population, which can lead to pandemic. H5N1 avian influenza virus is a major threat for emergence of a pandemic virus. As of June 12th, 2007, the virus has been reported in 45 countries, and 312 human cases with 190 deaths have been confirmed. We describe here substitutions at position 129 and 134 identified in a virus isolated from a fatal human case that could change the receptor-binding preference of HA of H5N1 virus from SA2,3Gal to both SA2,3Gal and SA2,6Gal. Molecular modeling demonstrated that the mutation may stabilize SA2,6Gal in its optimal cis conformation in the binding pocket. The mutation was found in approximately half of the viral sequences directly amplified from a respiratory specimen of the patient. Our data confirm the presence of H5N1 virus with the ability to bind to human-type receptor in this patient and suggest the selection and expansion of the mutant with human-type receptor specificity in human host environment.