An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus

Basis for Its Broad Cell Tropism

Hao Song, Jianxun Qi, Zahra Khedri, Sandra Diaz, Hai Yu, Xi Chen, Ajit Varki, Yi Shi, George F. Gao

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere1005411
JournalPLoS Pathogens
Volume12
Issue number1
DOIs
StatePublished - 2016

Fingerprint

Thogotovirus
Tropism
Glycoproteins
Influenzavirus C
Public Health
Sialic Acids
Virus Internalization
Pandemics
hemagglutinin esterase
Orthomyxoviridae
Human Influenza
Polysaccharides
Swine
Viruses

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus : Basis for Its Broad Cell Tropism. / Song, Hao; Qi, Jianxun; Khedri, Zahra; Diaz, Sandra; Yu, Hai; Chen, Xi; Varki, Ajit; Shi, Yi; Gao, George F.

In: PLoS Pathogens, Vol. 12, No. 1, e1005411, 2016.

Research output: Contribution to journalArticle

Song, Hao ; Qi, Jianxun ; Khedri, Zahra ; Diaz, Sandra ; Yu, Hai ; Chen, Xi ; Varki, Ajit ; Shi, Yi ; Gao, George F. / An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus : Basis for Its Broad Cell Tropism. In: PLoS Pathogens. 2016 ; Vol. 12, No. 1.
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