OmniVira

Multivalent interactions between fully glycosylated influenza virus hemagglutinins mediated by glycans at distinct N-glycosylation sites.

Ruofan Li1,2,3 Jingjing Gao1,4 Lin Wang1,5 Miao Gui6 Ye Xiang7,8,9
Affiliations 9 institutions
  1. Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, School of Basic Medical Sciences, Tsinghua University, 100084, Beijing, China.
  2. SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Shanxi Medical University, 030001, Taiyuan, Shanxi Province, China.
  3. Tsinghua-Peking Center for Life Sciences, 100084, Beijing, China.
  4. Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.
  5. Guangzhou National Laboratory, 510320, Guangzhou, China.
  6. Department of Obstetrics and Gynecology, Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine and Liangzhu Laboratory, 310016, Hangzhou, China. [email protected].
  7. Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, School of Basic Medical Sciences, Tsinghua University, 100084, Beijing, China. [email protected].
  8. SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Shanxi Medical University, 030001, Taiyuan, Shanxi Province, China. [email protected].
  9. Tsinghua-Peking Center for Life Sciences, 100084, Beijing, China. [email protected].
PMID40295773 DOI10.1038/s44298-024-00059-9 Year2024 Journal Npj viruses Npj Viruses Languageeng Publication statusActive
Active Last checked 2026-10-01 03:31:09 Source: NCBI PubMed

Abstract

The hemagglutinin (HA) glycoprotein of influenza virus binds host cell receptors and mediates viral entry. Here we present cryo-EM structures of fully glycosylated HAs from H5N1 and H5N8 influenza viruses. We find that the H5N1 HA can form filaments that comprise two head-to-head HA trimers. Multivalent interactions between the two HA trimers are mediated by glycans attached to N158. The distal Sia1-Gal2-NAG3 sugar moiety of N158 interacts with the receptor binding site on the opposing HA trimer. Additional interactions are observed between NAG3 and residues K222 and K193. The H5N8 HA lacks the N158 glycosylation site and does not form the filamentous structure. However, the H5N8 HA exhibits an auto-inhibition conformation, where the receptor binding site is occupied by the glycan chain attached to residue N169 from a neighboring protomer. These structures represent native HA-glycan interactions, which may closely mimic the receptor-HA interactions on the cell surface.

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