An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism

PLoS Pathogens

George F. Gao¹  Hao Song¹  Zahra Khedri¹  Yi Shi²  Ajit Varki²  Xi Chen²  Hai Yu³  Sandra Diaz³  Jianxun Qi⁴ 

[1] CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China;University of California, Davis, Davis, California, United States of America;University of California, San Diego, La Jolla, California, United States of America;University of Chinese Academy of Sciences, Beijing, China

关键词: Swine;    Esterases;    Influenza A virus;    Crystal structure;    Microarrays;    Cell binding assay;    Receptor binding assays;    Cattle;   

DOI  :  10.1371/journal.ppat.1005411

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV) was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF) of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV) HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health.

【 授权许可】

CC BY