ACS Medicinal Chemistry Letters
Letter
(6) Munro, J. B.; Mothes, W. Structure and Dynamics of the Native
manuscript. All authors have read, edited, and approved the
final manuscript.
HIV-1 Env Trimer. J. Virol. 2015, 89 (11), 5752−5755.
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(7) Richard, J.; Prevost, J.; Alsahafi, N.; Ding, S.; Finzi, A. Impact of
Funding
HIV-1 Envelope Conformation on ADCC Responses. Trends
Microbiol. 2018, 26 (4), 253−265.
Funding was provided by Program Project (P01 GM 56550)
to M.C.G., A.F., and A.B.S.; this work was also supported by an
internal CRCHUM grant (for the HTS screening) awarded to
A.F., by a CIHR foundation grant #352417 to A.F., and by a
NIH R01 to A.F. and M.P. (AI129769) and to M.P.
(AI116274). A.F. is the recipient of a Canada Research
Chair on Retroviral Entry # RCHS0235. S.D. is the recipient of
a FRSQ postdoctoral fellowship award.
(8) Veillette, M.; Coutu, M.; Richard, J.; Batraville, L.-A.; Dagher,
O.; Bernard, N.; Tremblay, C.; Kaufmann, D. E.; Roger, M.; Finzi, A.
The HIV-1 Gp120 CD4-Bound Conformation Is Preferentially
Targeted by Antibody-Dependent Cellular Cytotoxicity-Mediating
Antibodies in Sera from HIV-1-Infected Individuals. J. Virol. 2015, 89
(1), 545−551.
(9) Forthal, D. N.; Finzi, A. Antibody-Dependent Cellular
Cytotoxicity (ADCC) in HIV Infection. AIDS 2018, 32 (17), 1.
(10) Haynes, B. F.; Gilbert, P. B.; McElrath, M. J.; Zolla-Pazner, S.;
Tomaras, G. D.; Alam, S. M.; Evans, D. T.; Montefiori, D. C.;
Karnasuta, C.; Sutthent, R.; et al. Immune-Correlates Analysis of an
HIV-1 Vaccine Efficacy Trial. N. Engl. J. Med. 2012, 366 (14), 1275−
1286.
Notes
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, US Army, the Department of
Defense, or the US Government.
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(11) Ding, S.; Tolbert, W. D.; Prevost, J.; Pacheco, B.; Coutu, M.;
The authors declare no competing financial interest.
Debbeche, O.; Xiang, S.-H.; Pazgier, M.; Finzi, A. A Highly
Conserved Gp120 Inner Domain Residue Modulates Env Con-
formation and Trimer Stability. J. Virol. 2016, 90 (19), 8395−8409.
ACKNOWLEDGMENTS
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The authors thank the CRCHUM BSL3 and Flow Cytometry
Platforms, Jean Duchaine and Dominic Salois from the IRIC
HTS platform, the FRQS AIDS and Infectious Diseases
network, and Mario Legault for cohort coordination and
clinical samples. Dr. Charles W. Ross, III and Drs. Simon
Berritt and Charles E. Hendrick (University of Pennsylvania)
are also acknowledged for their assistance obtaining mass
spectra and utilizing the mass-directed purification system,
respectively.
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(12) Prevost, J.; Richard, J.; Ding, S.; Pacheco, B.; Charlebois, R.;
Hahn, B. H.; Kaufmann, D. E.; Finzi, A. Envelope Glycoproteins
Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-
Infected Individuals. Virology 2018, 515, 38−45.
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(13) Veillette, M.; Desormeaux, A.; Medjahed, H.; Gharsallah, N.-E.;
Coutu, M.; Baalwa, J.; Guan, Y.; Lewis, G.; Ferrari, G.; Hahn, B. H.;
et al. Interaction with Cellular CD4 Exposes HIV-1 Envelope
Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotox-
icity. J. Virol. 2014, 88 (5), 2633−2644.
(14) Richard, J.; Veillette, M.; Brassard, N.; Iyer, S. S.; Roger, M.;
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Martin, L.; Pazgier, M.; Schon, A.; Freire, E.; Routy, J.-P.; et al.
CD4Mimetics Sensitize HIV-1-Infected Cells to ADCC. Proc. Natl.
Acad. Sci. U. S. A. 2015, 112 (20), e2687−94.
ABBREVIATIONS
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AIDS, acquired immunodeficiency syndrome; HIV-1, human
immunodeficiency virus type 1; HAART, highly active
antiretroviral therapies; Env, envelope glycoprotein; Ab,
antibodies; ADCC, antibody-dependent cellular cytotoxicity;
CD4i, CD4-induced; CD4mc, CD4 mimetic compounds;
CoRBS, coreceptor binding site; HTS, high throughput screen;
CBE, cell-based ELISA; HOS, human osteosarcoma; DMF,
N,N-dimethylformamide; DCM, dichloromethane; TFA, tri-
fluoroacetic acid; HATU, hexafluorophosphate azabenzotria-
zole tetramethyl uronium; DIPEA, diisopropylethylamine;
EDC, 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide;
ITC, isothermal titration calorimetry
(15) Guan, Y.; Pazgier, M.; Sajadi, M. M.; Kamin-Lewis, R.; Al-
Darmarki, S.; Flinko, R.; Lovo, E.; Wu, X.; Robinson, J. E.; Seaman,
M. S.; et al. Diverse Specificity and Effector Function among Human
Antibodies to HIV-1 Envelope Glycoprotein Epitopes Exposed by
CD4 Binding. Proc. Natl. Acad. Sci. U. S. A. 2013, 110 (1), e69−78.
(16) Arias, J. F.; Heyer, L. N.; von Bredow, B.; Weisgrau, K. L.;
Moldt, B.; Burton, D. R.; Rakasz, E. G.; Evans, D. T. Tetherin
Antagonism by Vpu Protects HIV-Infected Cells from Antibody-
Dependent Cell-Mediated Cytotoxicity. Proc. Natl. Acad. Sci. U. S. A.
2014, 111 (17), 6425−6430.
(17) Richard, J.; Prevost, J.; Ding, S.; Brassard, N.; Medjahed, H.;
Coutu, M.; Kaufmann, D. E.; Finzi, A.; von, B. B.; Evans, D. T. BST-2
Expression Modulates Small CD4-Mimetic Sensitization of HIV-1-
Infected Cells to Antibody-Dependent Cellular Cytotoxicity. J. Virol.
2017, 91 (11), e00219-17.
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