An Avian Influenza H5N1 Virus That Binds to a Human-Type Receptor

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http://jvi.asm.org/cgi/content/abstract/81/18/9950


Journal of Virology, September 2007, p. 9950-9955, Vol. 81, No. 18
0022-538X/07/$08.00+0 doi:10.1128/JVI.00468-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.[/SIZE]
An Avian Influenza H5N1 Virus That Binds to a Human-Type Receptor<sup>

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Prasert Auewarakul,¹^* Ornpreya Suptawiwat,¹ Alita Kongchanagul,¹ Chak Sangma,⁶ Yasuo Suzuki,⁷ Kumnuan Ungchusak,⁴ Suda Louisirirotchanakul,¹ Hatairat Lerdsamran,¹ Phisanu Pooruk,¹ Arunee Thitithanyanont,² Chakrarat Pittayawonganon,⁴ Chao-Tan Guo,⁷ Hiroaki Hiramatsu,⁷ Wipawee Jampangern,³ Supamit Chunsutthiwat,⁵ and Pilaipan Puthavathana¹ Faculty of Medicine, Siriraj Hospital,¹ Faculty of Science,² Faculty of Tropical Medicine,³ Mahidol University, Bangkok, Thailand; Bureau of Epidemiology,⁴ Department of Disease Control, Bangkok, Thailand,⁵ Faculty of Science, Kasetsart University, Bangkok, Thailand,⁶ College of Life and Health Sciences, Chubu University, Kasugai, Japan⁷
Received 5 March 2007/ Accepted 18 June 2007


<!-- ABS --> Avian influenza viruses preferentially recognize sialosugarchains terminating in sialic acid-

2,3-galactose (SA

2,3Gal),whereas human influenza viruses preferentially recognize SA

2,6Gal.A conversion to SA

2,6Gal specificity is believed to be one ofthe 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 emergenceof a pandemic virus. As of 12 June 2007, the virus has beenreported in 45 countries, and 312 human cases with 190 deathshave been confirmed. We describe here substitutions at position129 and 134 identified in a virus isolated from a fatal humancase that could change the receptor-binding preference of HAof H5N1 virus from SA

2,3Gal to both SA

2,3Gal and SA

2,6Gal. Molecularmodeling demonstrated that the mutation may stabilize SA

2,6Galin its optimal cis conformation in the binding pocket. The mutationwas found in approximately half of the viral sequences directlyamplified from a respiratory specimen of the patient. Our dataconfirm the presence of H5N1 virus with the ability to bindto a human-type receptor in this patient and suggest the selectionand expansion of the mutant with human-type receptor specificityin the human host environment.