HIV-1 Vpu restricts Fc-mediated effector functions in vivo

SUMMARY
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 vpudefective 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.

Auteur(s) : Prévost, J., & al.