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Article

Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells

by
Guillaume Beaudoin-Bussières
1,2,†,
Jérémie Prévost
1,2,†,
Gabrielle Gendron-Lepage
1,
Bruno Melillo
3,
Junhua Chen
3,
Amos B. Smith III
3,
Marzena Pazgier
4 and
Andrés Finzi
1,2,*
1
Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada
2
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H3T 1J4, Canada
3
Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323, USA
4
Infectious Diseases Division, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Microorganisms 2020, 8(5), 710; https://doi.org/10.3390/microorganisms8050710
Submission received: 24 March 2020 / Revised: 30 April 2020 / Accepted: 9 May 2020 / Published: 11 May 2020
(This article belongs to the Special Issue Structural and Functional Biology of Retroviral Entry)
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Abstract

HIV-1-infected individuals raise a polyclonal antibody response targeting multiple envelope glycoprotein (Env) epitopes. Interestingly, two classes of non-neutralizing CD4-induced (CD4i) antibodies, present in the majority of HIV-1-infected individuals have been described to mediate antibody-dependent cellular cytotoxicity (ADCC) in the presence of small CD4 mimetic compounds (CD4mc). These antibodies recognize the coreceptor binding site (CoRBS) and the constant region one and two (C1C2 or inner domain cluster A) of the gp120. In combination with CD4mc they have been shown to stabilize an antibody-vulnerable Env conformation, known as State 2A. Here we evaluated the importance of these two families of Abs in ADCC responses by immunizing guinea pigs with gp120 immunogens that have been modified to elicit or not these types of antibodies. Underlying the importance of anti-CoRBS and anti-cluster A Abs in stabilizing State 2A, ADCC responses were only observed in the presence of these two types of CD4i antibodies. Altogether, our results suggest that these two families of CD4i antibodies must be taken into account when considering future strategies relying on the use of CD4mc to eliminate HIV-1-infected cells in vivo.
Keywords: HIV-1; ADCC; cluster A; coreceptor binding site; guinea pigs; small CD4 mimetics HIV-1; ADCC; cluster A; coreceptor binding site; guinea pigs; small CD4 mimetics

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MDPI and ACS Style

Beaudoin-Bussières, G.; Prévost, J.; Gendron-Lepage, G.; Melillo, B.; Chen, J.; Smith III, A.B.; Pazgier, M.; Finzi, A. Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells. Microorganisms 2020, 8, 710. https://doi.org/10.3390/microorganisms8050710

AMA Style

Beaudoin-Bussières G, Prévost J, Gendron-Lepage G, Melillo B, Chen J, Smith III AB, Pazgier M, Finzi A. Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells. Microorganisms. 2020; 8(5):710. https://doi.org/10.3390/microorganisms8050710

Chicago/Turabian Style

Beaudoin-Bussières, Guillaume, Jérémie Prévost, Gabrielle Gendron-Lepage, Bruno Melillo, Junhua Chen, Amos B. Smith III, Marzena Pazgier, and Andrés Finzi. 2020. "Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells" Microorganisms 8, no. 5: 710. https://doi.org/10.3390/microorganisms8050710

APA Style

Beaudoin-Bussières, G., Prévost, J., Gendron-Lepage, G., Melillo, B., Chen, J., Smith III, A. B., Pazgier, M., & Finzi, A. (2020). Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells. Microorganisms, 8(5), 710. https://doi.org/10.3390/microorganisms8050710

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