Journal
CELL REPORTS
Volume 41, Issue 6, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.111624
Keywords
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Categories
Funding
- Fred Hutchinson Cancer Research Center [QA255-006, QA255-067, QA255-072]
- James Robinson (Tulane University) [7B2, 2.2B, 12.3D, 12.4H, A32, C11, 17b]
- George Lewis (University of Maryland) [M785U1, M785U2, M785U3, M785U4, N5U1, N5U2, N5U3, N10U1, N10U2]
- Gunilla Karlsson Hedestam (Karolinska Institutet) [GE2-JG8]
- John Mascola (Vaccine Research Center, NIAID) [VRC01, VRC03, VRC07-523, VRC13, VRC16, VRC34]
- Mark Connors (NIAID) [10E8, N6, 35O22]
- Florian Klein (University of Cologne) [1-18]
- International AIDS Vaccine Initiative (IAVI) [PG9, PG16, PGT121, PGT122, PGT123, PGT125, PGT126, PGT128, PGT130, PGT135, PGT136, PGT145, PGT151]
- Canadian Institutes of Health Research (CIHR) foundation [352417]
- CIHR [422148]
- Canada Foundation for Innovation (CFI) [41027]
- National Institutes of Health [R01 AI148379, R01 AI150322, R01 AI129769, AI116274, R01 AI145164, R33 AI122384, P50 AI150464, P01 GM56550/AI150471]
- National Heart, Lung, and Blood Institute [1UM1AI164562-01]
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute on Drug Abuse
- National Institute of Allergy and Infectious Diseases
- Canada Research Chair on Retroviral Entry [RCHS0235 950-232424]
- German Research Foundation (DFG) [CRC 1279, SPP1923]
- Baden-Wurttemberg Foundation [BWST-ISF2018-032]
- Gruber Science Fellowship
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Non-neutralizing antibodies can eliminate HIV-1-infected cells through antibody-dependent cellular cytotoxicity. Restoring Vpu expression reduces nnAbs recognition of infected cells. The use of CD4-mimetics can make wild-type viruses sensitive to nnAbs effector functions.
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.
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