@article{3b42a81301f3442199a5ca92ff1a53ef,
title = "Two Families of Env Antibodies Efficiently Engage Fc-Gamma Receptors and Eliminate HIV -1-Infected Cells",
abstract = "HIV -1 conceals epitopes of its envelope glycoproteins (Env) recognized by antibody (Ab)-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These Abs, including anti-coreceptor binding site (CoRBS) and anti-cluster A antibodies, preferentially recognize Env in its {"}open{"} conformation. The binding of anti-CoRBS Abs has been shown to induce conformational changes that further open Env, allowing interaction of anti-cluster A antibodies. We explored the possibility that CoRBS Abs synergize with anti-cluster A Abs to engage Fc-gamma receptors to mediate ADCC. We found that binding of anti-CoRBS and anti-cluster A Abs to the same gp120 is required for interaction with soluble dimeric FcRIIIa in enzymelinked immunosorbent assays (ELISAs). We also found that Fc regions of both Abs are required to optimally engage FcRIIIa and mediate robust ADCC. Taken together, our results indicate that these two families of Abs act together in a sequential and synergistic fashion to promote FcRIIIa engagement and ADCC.",
keywords = "Adcc, Anti-cluster a antibodies, Anticoreceptor binding site antibodies, Cd4-mimetics, Env, Fcriiia, HIV -1, Nonneutralizing antibodies",
author = "Anand, {Sai Priya} and J{\'e}r{\'e}mie Pr{\'e}vost and Sophie Baril and Jonathan Richard and Halima Medjahed and Chapleau, {Jean Philippe} and Tolbert, {William D.} and Sharon Kirk and Smith, {Amos B.} and Wines, {Bruce D.} and Kent, {Stephen J.} and Hogarth, {P. Mark} and Parsons, {Matthew S.} and Marzena Pazgier and Andr{\'e}s Finzi",
note = "Funding Information: This work was supported by CIHR foundation grant 352417 to A.F. Support for this work was also provided by NIH via NIH grants NIAID R01 to A.F. and M.P. (AI129769) and NIAID R01 to M.P. (AI116274). A.F. is the recipient of a Canada Research Chair on Retroviral Entry (no. RCHS0235). J.R. is the recipient of Mathilde Krim Fellowships in Basic Biomedical Research from amfAR. J.P. is the recipient of a CIHR PhD fellowship award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We declare that we have no competing interests. Funding Information: We thank Dominique Gauchat of the CRCHUM Flow Cytometry Platform for technical assistance and Mario Legault for cohort coordination and clinical samples. This work was supported by CIHR foundation grant 352417 to A.F. Support for this work was also provided by NIH via NIH grants NIAID R01 to A.F. and M.P. (AI129769) and NIAID R01 to M.P. (AI116274). A.F. is the recipient of a Canada Research Chair on Retroviral Entry (no. RCHS0235). J.R. is the recipient of Mathilde Krim Fellowships in Basic Biomedical Research from amfAR. J.P. is the recipient of a CIHR PhD fellowship award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We declare that we have no competing interests. The views expressed in this presentation are those of the authors and do not reflect the official policy or position of the Uniformed Services University, U.S. Army, the Department of Defense, or the U.S. Government. Publisher Copyright: Copyright {\textcopyright} 2019 American Society for Microbiology.",
year = "2019",
month = feb,
day = "1",
doi = "10.1128/JVI.01823-18",
language = "English",
volume = "93",
journal = "Journal of Virology",
issn = "0022-538X",
number = "3",
}