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Title: Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants

Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Viet Nam/1203/04 and A/Indonesia/5/05 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6 linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3 linked sialosides. Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogues reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses.
Authors:
 [1] ;  [2] ;  [2] ;  [1] ;  [2] ;  [3]
  1. Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology
  2. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Singapore-MIT Alliance for Research and Technology, Koch Institute of Integrative Cancer Research
  3. Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology and Skaggs Inst. for Chemical Biology
Publication Date:
OSTI Identifier:
1242428
Grant/Contract Number:
AC02-06CH11357
Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 13; Journal Issue: 8; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Research Org:
Univ. of Chicago, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES