1. HIV-1 Vpu restricts Fc-mediated effector functions in vivo.
- Author
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Prévost J, Anand SP, Rajashekar JK, Zhu L, Richard J, Goyette G, Medjahed H, Gendron-Lepage G, Chen HC, Chen Y, Horwitz JA, Grunst MW, Zolla-Pazner S, Haynes BF, Burton DR, Flavell RA, Kirchhoff F, Hahn BH, Smith AB 3rd, Pazgier M, Nussenzweig MC, Kumar P, and Finzi A
- Subjects
- Animals, Humans, Mice, Antibodies, Neutralizing, Antibody-Dependent Cell Cytotoxicity, HIV Antibodies, HIV Infections, HIV Seropositivity, HIV-1
- Abstract
Non-neutralizing antibodies (nnAbs) can eliminate HIV-1-infected cells via antibody-dependent cellular cytotoxicity (ADCC) and were identified as a correlate of protection in the RV144 vaccine trial. Fc-mediated effector functions of nnAbs were recently shown to alter the course of HIV-1 infection in vivo using a vpu-defective virus. Since Vpu is known to downregulate cell-surface CD4, which triggers conformational changes in the viral envelope glycoprotein (Env), we ask whether the lack of Vpu expression was linked to the observed nnAbs activity. We find that restoring Vpu expression greatly reduces nnAb recognition of infected cells, rendering them resistant to ADCC. Moreover, administration of nnAbs in humanized mice reduces viral loads only in animals infected with a vpu-defective but not with a wild-type virus. CD4-mimetics administration, known to "open" Env and expose nnAb epitopes, renders wild-type viruses sensitive to nnAbs Fc-effector functions. This work highlights the importance of Vpu-mediated evasion of humoral responses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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