Enhancement of CD4 Binding, Host Cell Entry, and Sensitivity to CD4bs Antibody Inhibition Conferred by a Natural but Rare Polymorphism in the HIV-1 Envelope

Author:

Ratcliff Annette N.1,Venner Colin M.2,Olabode Abayomi S.3,Knapp Jason2,Pankrac Joshua2,Derecichei Iulian2,Gibson Richard M.4,Finzi Andrés5ORCID,Li Yue2,Mann Jamie F. S.26,Arts Eric J.124ORCID

Affiliation:

1. Department of Molecular Biology and Microbiology and Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio, USA

2. Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada

3. Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada

4. ImPaKT Facility, University of Western Ontario, London, Ontario, Canada

5. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada

6. Bristol Veterinary School, University of Bristol, Bristol, United Kingdom

Abstract

Typically, a natural amino acid polymorphism is found as the wild-type sequence in the HIV-1 population if it provides a selective advantage to the virus. The natural K425 polymorphism in HIV-1 Env results in higher host cell entry efficiency and greater replicative fitness by virtue of its high binding affinity to CD4.

Funder

Canada Foundation for Innovation

Canada Research Chairs

Gouvernement du Canada | Canadian Institutes of Health Research

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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