An avian influenza H5N1 virus that binds to a human-type receptor.
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.
Auewarakul
Prasert
P
Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. sipaw@mahidol.ac.th
Suptawiwat
Ornpreya
O
Kongchanagul
Alita
A
Sangma
Chak
C
Suzuki
Yasuo
Y
Ungchusak
Kumnuan
K
Louisirirotchanakul
Suda
S
Lerdsamran
Hatairat
H
Pooruk
Phisanu
P
Thitithanyanont
Arunee
A
Pittayawonganon
Chakrarat
C
Guo
Chao-Tan
CT
Hiramatsu
Hiroaki
H
Jampangern
Wipawee
W
Chunsutthiwat
Supamit
S
Puthavathana
Pilaipan
P
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*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid