{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:17:54Z","timestamp":1791047874200,"version":"4.1.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2012,7,15]],"date-time":"2012-07-15T00:00:00Z","timestamp":1342310400000},"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":["J Virol"],"published-print":{"date-parts":[[2012,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Human immunodeficiency virus type 1 (HIV-1) infection can spread efficiently from infected to uninfected T cells through adhesive contacts called virological synapses (VSs). In this process, cell-surface envelope glycoprotein (Env) initiates adhesion and viral transfer into an uninfected recipient cell. Previous studies have found some HIV-1-neutralizing patient sera to be less effective at blocking VS-mediated infection than infection with cell-free virus. Here we employ sensitive flow cytometry-based infection assays to measure the inhibitory potency of HIV-1-neutralizing monoclonal antibodies (MAb) and HIV-1-neutralizing patient sera against cell-free and VS-mediated infection. To various degrees, anti-Env MAbs exhibited significantly higher 50% inhibitory concentration (IC<jats:sub>50<\/jats:sub>s) against VS-mediated infection than cell-free infection. Notably, the MAb 17b, which binds a CD4-induced (CD4i) epitope on gp120, displayed a 72-fold reduced efficacy against VS-mediated inocula compared to cell-free inocula. A mutant with truncation mutation in the gp41 cytoplasmic tail (CT) which is unable to modulate Env fusogenicity in response to virus particle maturation but which can still engage in cell-to-cell infection was tested for the ability to resist neutralizing antibodies. The \u0394CT mutation increased cell surface staining by neutralizing antibodies, significantly enhanced neutralization of VS-mediated infection, and had reduced or no effect on cell-free infection, depending upon the antibody. Our results suggest that the gp41 CT regulates the exposure of key neutralizing epitopes during cell-to-cell infection and plays an important role in immune evasion. Vaccine strategies should consider immunogens that reflect Env conformations exposed on the infected cell surface to enhance protection against VS-mediated HIV-1 spread.<\/jats:p>","DOI":"10.1128\/jvi.00230-12","type":"journal-article","created":{"date-parts":[[2012,5,3]],"date-time":"2012-05-03T01:53:16Z","timestamp":1336009996000},"page":"7484-7495","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":71,"title":["Neutralization Resistance of Virological Synapse-Mediated HIV-1 Infection Is Regulated by the gp41 Cytoplasmic Tail"],"prefix":"10.1128","volume":"86","author":[{"given":"Natasha D.","family":"Durham","sequence":"first","affiliation":[{"name":"Microbiology Graduate School Training Program, Department of Microbiology"},{"name":"Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice W.","family":"Yewdall","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chati","family":"Zony","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tulane University Medical Center, New Orleans, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin K.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, New York, 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