{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:02:03Z","timestamp":1760151723619,"version":"build-2065373602"},"reference-count":92,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI140909"],"award-info":[{"award-number":["AI140909"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>HIV-1 Env signal peptide (SP) is an important contributor to Env functions. Env is generated from Vpu\/Env encoded bicistronic mRNA such that the 5\u2032 end of Env-N-terminus, that encodes for Env-SP overlaps with 3\u2032 end of Vpu. Env SP displays high sequence diversity, which translates into high variability in Vpu sequence. This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. We used infectious molecular clone pNL4.3-CMU06 and swapped its SP (or VEOR) with that from other HIV-1 isolates. Swapping VEOR did not affect virus production in the absence of tetherin however, presence of tetherin significantly altered the release of virus progeny. VEOR also altered Vpu\u2019s ability to downregulate CD4 and tetherin. We next tested the effect of these swaps on Env functions. Analyzing the binding of monoclonal antibodies to membrane embedded Env revealed changes in the antigenic landscape of swapped Envs. These swaps affected the oligosaccharide composition of Env-N-glycans as shown by changes in DC-SIGN-mediated virus transmission. Our study suggests that genetic diversity in VEOR plays an important role in the differential pathogenesis and also assist in immune evasion by altering Env epitope exposure.<\/jats:p>","DOI":"10.3390\/v14040808","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T23:07:16Z","timestamp":1649891236000},"page":"808","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion"],"prefix":"10.3390","volume":"14","author":[{"given":"Chitra","family":"Upadhyay","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka Gadam","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roya","family":"Feyznezhad","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/334532a0","article-title":"Identification of a protein encoded by the vpu gene of HIV-1","volume":"334","author":"Cohen","year":"1988","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00934-16","DOI":"10.1128\/mBio.00934-16","article-title":"Vpu-Mediated Counteraction of Tetherin Is a Major Determinant of HIV-1 Interferon Resistance","volume":"7","author":"Kmiec","year":"2016","journal-title":"mBio"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5448","DOI":"10.1128\/jvi.64.11.5448-5456.1990","article-title":"Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple bicistronic mRNAs","volume":"64","author":"Schwartz","year":"1990","journal-title":"J. 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