Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses-Reference-Cited by-同舟云学术

Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses

Published:2020-06-19 Issue:6497 Volume:368 Page:1335-1340
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Wu Nicholas C.¹^ORCID,Thompson Andrew J.²^ORCID,Lee Juhye M.³⁴⁵^ORCID,Su Wen⁶,Arlian Britni M.²,Xie Jia⁷^ORCID,Lerner Richard A.⁷⁸^ORCID,Yen Hui-Ling⁶^ORCID,Bloom Jesse D.³⁴⁹^ORCID,Wilson Ian A.¹⁸^ORCID

Affiliation:

1. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

2. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

3. Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

4. Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.

5. Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA.

6. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

7. Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.

8. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

9. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Abstract

Resistance to influenza antibodies Broadly neutralizing human antibodies (bnAbs) to the stem of hemagglutinin (HA), a trimeric glycoprotein found on the surface of influenza viruses, are valuable therapeutics and can guide the development of universal influenza vaccines. For their use in therapy development, it is important to understand the extent to which HA stem variants with resistance to bnAbs can develop. Wu et al. used saturation mutagenesis combined with next-generation sequencing to systematically search for resistance mutations to prototypic bnAbs in two influenza subtypes, H3 and H1. They found that the genetic barrier to resistance to stem bnAbs was low for the H3 subtype but higher for the H1 subtype. The ability of H3 to develop resistance to bnAbs presents a challenge in the development of a universal influenza vaccine. Science , this issue p. 1335

Funder

National Institutes of Health

Bill and Melinda Gates Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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