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Title: A human-infecting H10N8 influenza virus retains a strong preference for avian-type receptors

Recent avian-origin H10N8 influenza A viruses that have infected humans pose a potential pandemic threat. Alterations in the viral surface glycoprotein, hemagglutinin (HA), typically are required for influenza A viruses to cross the species barrier for adaptation to a new host, but whether H10N8 contains adaptations supporting human infection remains incompletely understood. In this paper, we investigated whether H10N8 HA can bind human receptors. Sialoside glycan microarray analysis showed that the H10 HA retains a strong preference for avian receptor analogs and negligible binding to human receptor analogs. Crystal structures of H10 HA with avian and human receptor analogs revealed the basis for preferential recognition of avian-like receptors. Furthermore, introduction of mutations into the H10 receptor-binding site (RBS) known to convert other HA subtypes from avian to human receptor specificity failed to switch preference to human receptors. In conclusion, collectively these findings suggest that the current H10N8 human isolates are poorly adapted for efficient human-to-human transmission.
Authors:
 [1] ;  [2] ;  [3] ;  [3] ;  [3] ;  [3] ;  [3] ;  [3]
  1. The Scripps Research Institute, La Jolla, CA (United States); Chinese Academy of Sciences (CAS), Beijing (China)
  2. The Scripps Research Institute, La Jolla, CA (United States); Utrecht Univ. (The Netherlands)
  3. The Scripps Research Institute, La Jolla, CA (United States)
Publication Date:
Grant/Contract Number:
R56 AI099275; AI099274; Y1-CO-1020; Y1-GM-1104; GM62116; P41GM103393; P41RR001209
Type:
Published Article
Journal Name:
Cell Host & Microbe
Additional Journal Information:
Journal Volume: 17; Journal Issue: 3; Journal ID: ISSN 1931-3128
Publisher:
Elsevier
Research Org:
The Scripps Research Inst., La Jolla, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Inst. of Health (NIH) (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES
OSTI Identifier:
1241402
Alternate Identifier(s):
OSTI ID: 1233921; OSTI ID: 1347138