{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:11:59Z","timestamp":1788959519121,"version":"build-2803163510"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The HIV-1 envelope glycoprotein (Env) represents the only viral antigen at the surface of infected cells, making it an ideal target for antibody-based therapies. Most antibodies elicited in people with HIV (PWH) do not recognize Env in its native \u201cclosed\u201d conformation but readily bind to Env when it samples the CD4-bound \u201copen\u201d conformation. Downregulation of CD4 at the surface of infected cells by the viral accessory proteins Nef and Vpu prevents the premature opening of Env and has been shown to protect infected cells from antibody-dependent cellular cytotoxicity (ADCC) mediated by PWH plasma. Here, we report that deletion of Nef and Vpu from primary infectious molecular clones renders infected cells vulnerable to antibody-dependent cellular phagocytosis (ADCP) mediated by PWH plasma. This is in part linked to the premature engagement of Env with CD4. In agreement with an \u201copen\u201d Env being vulnerable to ADCP, small CD4-mimetic compounds (CD4mc) sensitize\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      -infected cells and\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      -expanded CD4 T cells to ADCP mediated by autologous monocytes in the presence of PWH plasma. This effect was further improved by increasing cell surface Env through IFN-induced BST-2 upregulation.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Developing new therapies to eliminate HIV-1-infected cells is essential to decrease the size of the HIV-1 reservoir. Fc-effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), have shown potential in eliminating\n                        <jats:italic toggle=\"yes\">in vitro-<\/jats:italic>\n                        infected cells and\n                        <jats:italic toggle=\"yes\">ex vivo-<\/jats:italic>\n                        expanded infected cells from people with HIV, decreasing the size of the reservoir, and delaying viral rebound in humanized mice. Here, we report that antibody-dependent cellular phagocytosis (ADCP) can also be harnessed to eliminate HIV-1-infected cells. We show that infected cells harboring \u201copen\u201d Env conformations are susceptible to ADCP-mediated killing in the presence of plasma from people with HIV. A better understanding of the contribution of different Fc-effector functions in the elimination of infected cells could help guide the development of new therapeutic approaches toward an HIV-1 cure.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01487-26","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:01:05Z","timestamp":1785330065000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Nef and Vpu protect infected cells from ADCP mediated by plasma from people with HIV-1"],"prefix":"10.1128","volume":"17","author":[{"given":"\u00c9tienne","family":"B\u00e9langer","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rgqcd02","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre de Recherche du CHUM","place":["Montreal, 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