6NHQ

Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin HA2 I45M mutant

Summary for 6NHQ

• Entry DOI: 10.2210/pdb6nhq/pdb
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: viral protein
• Biological source: Influenza A virus (strain A/Hong Kong/1/1968 H3N2); More
• Total number of polymer chains: 6
• Total formula weight: 171454.89

Authors

Wu, N.C.,Wilson, I.A. (deposition date: 2018-12-23, release date: 2020-04-15, Last modification date: 2024-10-09)

Primary citation

Wu, N.C.,Thompson, A.J.,Lee, J.M.,Su, W.,Arlian, B.M.,Xie, J.,Lerner, R.A.,Yen, H.L.,Bloom, J.D.,Wilson, I.A.
Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses.
Science, 368:1335-1340, 2020

PubMed Abstract: The discovery and characterization of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the genetic barrier to resistance to stem bnAbs is low for the H3 subtype but substantially higher for the H1 subtype owing to structural differences in the HA stem. Several strong resistance mutations in H3 can be observed in naturally circulating strains and do not reduce in vitro viral fitness and in vivo pathogenicity. This study highlights a potential challenge for development of a truly universal influenza vaccine.

PubMed: 32554590
DOI: 10.1126/science.aaz5143

Experimental method

X-RAY DIFFRACTION (2.5 Å)