{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:15:35Z","timestamp":1787030135854,"version":"build-2736575974"},"reference-count":112,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01AI176897"],"award-info":[{"award-number":["R01AI176897"]}]},{"name":"National Institutes of Health","award":["R01AI172547"],"award-info":[{"award-number":["R01AI172547"]}]},{"name":"National Institutes of Health","award":["R21AI89232"],"award-info":[{"award-number":["R21AI89232"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Adaptor protein (AP) complexes are critical components of the cellular membrane transport machinery. They mediate cargo selection during endocytosis and intracellular vesicular trafficking. Five AP complexes have been characterized (AP1-5), and together their roles extend to diverse cellular processes including the homeostasis of membranous organelles, membrane protein turnover, and immune responses. Human Immunodeficiency Virus type 1 (HIV-1) and other lentiviruses co-opt these complexes to support immune evasion and the assembly of maximally infectious particles. HIV-1 Nef interacts with AP1 and AP2 to manipulate intracellular trafficking and downregulate immune-related proteins such as CD4 and MHC-I. Vpu also co-opts AP1 and AP2, modulating the innate defense protein BST2 (Tetherin) and facilitating the release of virions from infected cells. The envelope glycoprotein (Env) hijacks AP complexes to reduce its expression at the cell surface and potentially support incorporation into virus particles. Some data suggest that Gag co-opts AP3 to drive assembly at intracellular compartments. In principle, targeting the molecular interfaces between HIV-1 proteins and AP complexes is a promising therapeutic approach. Blocking these interactions should impair HIV-1\u2019s ability to produce infectious particles and evade immune defenses, leading to novel antivirals and facilitating a cure.<\/jats:p>","DOI":"10.3390\/v17050715","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T06:57:28Z","timestamp":1747378648000},"page":"715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Adaptor Protein Complexes in HIV-1 Pathogenesis: Mechanisms and Therapeutic Potential"],"prefix":"10.3390","volume":"17","author":[{"given":"Maria Elena","family":"Barone","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Woody","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3650-6495","authenticated-orcid":false,"given":"Parisa","family":"Taklifi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatema","family":"Yeasmin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA"},{"name":"Department of Chemistry and Biochemistry, University of Massachusetts, Dartmouth, MA 02747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kequan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA"},{"name":"Department of Chemistry and Biochemistry, University of Massachusetts, Dartmouth, MA 02747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3784-9660","authenticated-orcid":false,"given":"Mary K.","family":"Lewinski","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-6936","authenticated-orcid":false,"given":"Charlotte A.","family":"Stoneham","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-3884","authenticated-orcid":false,"given":"Xiaofei","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Guatelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"jcs222992","DOI":"10.1242\/jcs.222992","article-title":"Adaptor Protein Complexes and Disease at a Glance","volume":"132","author":"Sanger","year":"2019","journal-title":"J. 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