Although more than 100 people have been infected by H5N1 influenza A viruses, human-to-human transmission is rare¹. What are the molecular barriers limiting human-to-human transmission? Here we demonstrate an anatomical difference in the distribution in the human airway of the different binding molecules preferred by the avian and human influenza viruses. The respective molecules are sialic acid linked to galactose by an -2,3 linkage (SA2,3Gal) and by an -2,6 linkage (SA2,6Gal)². Our findings may provide a rational explanation for why H5N1 viruses at present rarely infect and spread between humans although they can replicate efficiently in the lungs.

1. Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA
2. Division of Virology, Department of Microbiology and Immunology, University of Tokyo, Tokyo 108-8639, Japan
3. International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
4. Institute for Animal Experimentation, Tohoku University, Sendai, Miyagi 980-8575, Japan
5. Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan
6. Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan
7. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
8. Present address: The Avian Zoonosis Research Centre, Tottori University, Tottori 680-8550, Japan

Correspondence to: Yoshihiro Kawaoka^1,2,3,7 Email: kawaokay@svm.vetmed.wisc.edu

Received 12 February 2006 | Accepted 9 March 2006 |

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