decoding the distribution of glycan receptors for human-adapted influenza a viruses in ferret respiratory tract解码的多糖受体分布的人适应甲型流感病毒在雪貂呼吸道.pdf

Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract 1 1 1 1 2 Akila Jayaraman , Aarthi Chandrasekaran , Karthik Viswanathan , Rahul Raman , James G. Fox , Ram Sasisekharan1* 1 Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Department of Biological Engineering, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts, United States of America, 2 Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United State of America Abstract Ferrets are widely used as animal models for studying influenza A viral pathogenesis and transmissibility. Human-adapted influenza A viruses primarily target the upper respiratory tract in humans (infection of the lower respiratory tract is observed less frequently), while in ferrets, upon intranasal inoculation both upper and lower respiratory tract are targeted. Viral tropism is governed by distribution of complex sialylated glycan receptors in various cells/tissues of the host that are specifically recognized by influenza A virus hemagglutinin (HA), a glycoprotein on viral surface. It is generally known that upper respiratory tract of humans and ferrets predominantly express a2R6 sialylated glycan receptors. However much less is known about the fine structure of these glycan receptors and their distribution in different regions of the ferret respiratory tract. In this study, we characterize distribution of glycan receptors going beyond terminal sialic acid linkage in the cranial and caudal regions of the ferret trache