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J Virol. 2019 Sep 4. pii: JVI.01403-19. doi: 10.1128/JVI.01403-19. [Epub ahead of print]

CD4 Incorporation into HIV-1 Viral Particles Exposes Envelope Epitopes Recognized by CD4-induced Antibodies.

Author information

1
Centre de Recherche du CHUM, QC, Canada.
2
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada.
3
Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
4
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
5
Department of Microbiology, Harvard Medical School, Boston, MA, USA.
6
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
7
Infectious Diseases Division, Department of Medicine of Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
8
Centre de Recherche du CHUM, QC, Canada andres.finzi@umontreal.ca.

Abstract

CD4 downregulation on infected cells is a highly conserved function of primate lentiviruses. It has been shown to positively impact viral replication by a variety of mechanisms including enhanced viral release and infectivity, decrease of cell reinfection and protection from antibody-dependent cellular cytotoxicity (ADCC), which is often mediated by antibodies that require CD4 to change envelope (Env) conformation. Here we report that incorporation of CD4 into HIV-1 viral particles affects Env conformation resulting in the exposure of occluded epitopes recognized by CD4-induced antibodies. This translates into enhanced neutralization susceptibility by these otherwise non-neutralizing antibodies but is prevented by the HIV-1 Nef accessory protein. Altogether, these findings suggest that another functional consequence of Nef-mediated CD4 downregulation is the protection of viral particles from neutralization by commonly-elicited CD4-induced antibodies.IMPORTANCE It has been well established that Env-CD4 complexes expose epitopes recognized by commonly-elicited CD4-induced antibodies at the surface of HIV-1-infected cells, rendering them vulnerable to ADCC responses. Here we show that CD4 incorporation has a profound impact on Env conformation at the surface of viral particles. Incorporated CD4 exposes CD4-induced epitopes on Env, rendering HIV-1 susceptible to neutralization by otherwise non-neutralizing antibodies.

PMID:
31484748
DOI:
10.1128/JVI.01403-19

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