{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:45:42Z","timestamp":1781102742464,"version":"3.54.1"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"13","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["108079\/Z\/15\/Z"],"award-info":[{"award-number":["108079\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG CRC 1279 and SPP 1923"],"award-info":[{"award-number":["DFG CRC 1279 and SPP 1923"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,3,31]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Lentiviruses encode accessory proteins to manipulate their host cells in order to efficiently replicate and evade antiviral defenses. Interestingly, most lentiviral Nefs down-regulate CD3 from the surface of infected T cells to perturb immune responses. However, for reasons that are incompletely understood, HIV-1 and its simian immunodeficiency virus ancestors lack this function. Here, we report that engineering HIV-1 for Nef-mediated down-regulation of CD3 reduces Env-dependent HIV-1 infectivity, resulting in less efficient cell-to-cell spread and replication. Our data suggest that HIV-1 may have evolved to lose the CD3 down-modulation function of Nef in order to allow T cell activation and to boost viral replication, possibly at the cost of less effective immune evasion and increased pathogenicity.<\/jats:p>","DOI":"10.1073\/pnas.1921135117","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T20:25:53Z","timestamp":1584390353000},"page":"7382-7391","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Loss of Nef-mediated CD3 down-regulation in the HIV-1 lineage increases viral infectivity and spread"],"prefix":"10.1073","volume":"117","author":[{"given":"Dejan","family":"Mesner","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity, University College London, London WC1E 6BT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Hotter","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7052-2360","authenticated-orcid":false,"given":"Frank","family":"Kirchhoff","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4603-2281","authenticated-orcid":false,"given":"Clare","family":"Jolly","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, University College London, London WC1E 6BT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1217550"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006841"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.04.008"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2018.02.005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.12.002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/v8030067"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12412"},{"key":"e_1_3_3_8_2","first-page":"147","article-title":"Implications of Nef: Host cell interactions in viral persistence and progression to AIDS","volume":"339","author":"Arhel N. 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