title: An avian influenza H5N1 virus that binds to a human-type receptor.
abstract: Avian influenza viruses preferentially recognize sialosugar chains terminating in sialic acid-alpha2,3-galactose (SAalpha2,3Gal), whereas human influenza viruses preferentially recognize SAalpha2,6Gal. A conversion to SAalpha2,6Gal specificity is believed to be one of the changes required for the introduction of new hemagglutinin (HA) subtypes to the human population, which can lead to pandemics. Avian influenza H5N1 virus is a major threat for the emergence of a pandemic virus. As of 12 June 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 SAalpha2,3Gal to both SAalpha2,3Gal and SAalpha2,6Gal. Molecular modeling demonstrated that the mutation may stabilize SAalpha2,6Gal 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 a human-type receptor in this patient and suggest the selection and expansion of the mutant with human-type receptor specificity in the human host environment.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. sipaw@mahidol.ac.th
authors.forename: Prasert
authors.initials: P
authors.lastname: Auewarakul
authors.forename: Ornpreya
authors.initials: O
authors.lastname: Suptawiwat
authors.forename: Alita
authors.initials: A
authors.lastname: Kongchanagul
authors.forename: Chak
authors.initials: C
authors.lastname: Sangma
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kumnuan
authors.initials: K
authors.lastname: Ungchusak
authors.forename: Suda
authors.initials: S
authors.lastname: Louisirirotchanakul
authors.forename: Hatairat
authors.initials: H
authors.lastname: Lerdsamran
authors.forename: Phisanu
authors.initials: P
authors.lastname: Pooruk
authors.forename: Arunee
authors.initials: A
authors.lastname: Thitithanyanont
authors.forename: Chakrarat
authors.initials: C
authors.lastname: Pittayawonganon
authors.forename: Chao-Tan
authors.initials: CT
authors.lastname: Guo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hiramatsu
authors.forename: Wipawee
authors.initials: W
authors.lastname: Jampangern
authors.forename: Supamit
authors.initials: S
authors.lastname: Chunsutthiwat
authors.forename: Pilaipan
authors.initials: P
authors.lastname: Puthavathana
mesh_terms: D001665:Binding Sites / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007251:Influenza, Human / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid