Deep Mutational Scanning Comprehensively Maps How Zika Envelope Protein Mutations Affect Viral Growth and Antibody Escape

Author:

Sourisseau Marion1,Lawrence Daniel J. P.23ORCID,Schwarz Megan C.1,Storrs Carina H.1,Veit Ethan C.1,Bloom Jesse D.234ORCID,Evans Matthew J.1ORCID

Affiliation:

1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

2. Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

3. Department of Genome Sciences, University of Washington, Seattle, Washington, USA

4. Howard Hughes Medical Institute, Seattle, Washington, USA

Abstract

Zika virus has recently been shown to be associated with severe birth defects. The virus’s E protein mediates its ability to infect cells and is also the primary target of the antibodies that are elicited by natural infection and vaccines that are being developed against the virus. Therefore, determining the effects of mutations to this protein is important for understanding its function, its susceptibility to vaccine-mediated immunity, and its potential for future evolution. We completely mapped how amino acid mutations to the E protein affected the virus’s ability to grow in cells in the laboratory and escape from several antibodies. The resulting maps relate changes in the E protein’s sequence to changes in viral function and therefore provide a valuable complement to existing maps of the physical structure of the protein.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Howard Hughes Medical Institute

Burroughs Wellcome Fund

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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