Vpu protects HIV-infected cells from antibody-dependent cellular phagocytosis by counteracting tetherin
Year: 2026
Type: article
Abstract: Tetherin is an interferon-inducible transmembrane protein that inhibits the detachment of enveloped viruses from infected cells. HIV-1 Vpu counteracts this restriction by removing tetherin from sites of virus release. Accordingly, Vpu mutations that disrupt tetherin antagonism increase Env accumulation on the surface of HIV-infected cells. We found that Vpu mutations that impair tetherin antagonism also increase the susceptibility of HIV-infected cells to antibody-dependent cellular phagocytosis (ADCP). Increased sensitivity to ADCP was lost in tetherin-knockout cells and conditionally restored by doxycycline-inducible tetherin. Thus, Vpu protects HIV-infected cells from ADCP by preventing virion accumulation on the cell surface, similar to its protection against antibody-dependent cellular cytotoxicity (ADCC). By serving as a link between innate and adaptive immunity, the antiviral activity of tetherin may be amplified in vivo by Fc-mediated antibody effector functions and therefore much greater than initially appreciated based solely on its ability to inhibit virus release in cell culture assays.
Source: Cell Reports
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: Fcgamma receptor-mediated suppression of immunodeficiency virus replication, Assessing ADCC and Fc-mediated Protection against HIV, Tethering lentiviral restriction to Fc-mediated antibody responses, KIR and MHC Class I Immunogenetics in SIV Infection, G9000180070, Harnessing adaptive NK cell transfer to deplete viral reservoirs, Evaluation of didehydro-Cortistatin A as a block-and-lock agent for a functional HIV cure in a macaque model
OpenAlex ID: W7214940397