{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:34:07Z","timestamp":1777520047410,"version":"3.51.4"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>HIV particles in the blood largely originate from activated lymphocytes and can overshadow variants which may be expressed from other cell types. Investigations of virus persistence must be able to distinguish cells refractory to viral clearance that serve as reservoirs. To investigate additional cell types that may be associated with <jats:italic>in vivo<\/jats:italic> HIV expression we developed a virus particle immunomagnetic capture method targeting several markers of cellular origin that become embedded within virion envelopes during budding. We evaluated the ability of markers to better distinguish cell lineage source subpopulations by assessing combinations of different antibodies with cell-sorted <jats:italic>in vitro<\/jats:italic> culture and clinical specimens. Various deductive algorithms were designed to discriminate source cell lineages and subsets. From the particle capture algorithms, we identified distinct variants expressed within individuals that were associated with disparate cellular markers. Among the variants uncovered were minority-level viruses with drug resistance mutations undetected by sequencing and often were associated with markers indicative of myeloid lineage (CD3<jats:sup>-<\/jats:sup>\/CD10<jats:sup>-<\/jats:sup>\/CD16<jats:sup>+<\/jats:sup> or \/CD14<jats:sup>+<\/jats:sup>, and CD3<jats:sup>-<\/jats:sup>\/CD16<jats:sup>-<\/jats:sup>\/CD14<jats:sup>-<\/jats:sup>\/CD11c<jats:sup>+<\/jats:sup> or \/HLA-DR<jats:sup>+<\/jats:sup>) cell sources. The diverse HIV genetic sequences expressed from different cell types within individuals, further supported by the appearance of distinct drug-resistant variants, highlights the complexity of HIV reservoirs <jats:italic>in vivo<\/jats:italic> which must be considered for HIV cure strategies. This approach could also be helpful in examining <jats:italic>in vivo<\/jats:italic> host cell origins and genetic diversity in infections involving other families of budding viruses.<\/jats:p>","DOI":"10.1371\/journal.pone.0296891","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T18:22:16Z","timestamp":1709058136000},"page":"e0296891","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunocapture of cell surface proteins embedded in HIV envelopes uncovers considerable virion genetic diversity associated with different source cell types"],"prefix":"10.1371","volume":"19","author":[{"given":"Sarah","family":"Sabour","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-fen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan T.","family":"Lipscomb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariana P.","family":"Santos Tino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9202-846X","authenticated-orcid":true,"given":"Jeffrey A.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"issue":"2","key":"pone.0296891.ref001","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1172\/JCI86047","article-title":"Recent developments in the effort to cure HIV infection: going beyond N = 1","volume":"126","author":"JD Siliciano","year":"2016","journal-title":"J Clin Invest"},{"issue":"4","key":"pone.0296891.ref002","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/COH.0000000000000688","article-title":"Eliminating HIV reservoirs for a cure: the issue is in the tissue","volume":"16","author":"K Busman-Sahay","year":"2021","journal-title":"Curr Opin HIV AIDS"},{"issue":"12","key":"pone.0296891.ref003","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.3390\/v13122512","article-title":"Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection","volume":"13","author":"CY Lau","year":"2021","journal-title":"Viruses"},{"issue":"6629","key":"pone.0296891.ref004","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/387183a0","article-title":"Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection","volume":"387","author":"TW Chun","year":"1997","journal-title":"Nature"},{"issue":"9","key":"pone.0296891.ref005","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1086\/319864","article-title":"Residual human immunodeficiency virus (HIV) Type 1 RNA and DNA in lymph nodes and HIV RNA in genital secretions and in cerebrospinal fluid after suppression of viremia for 2 years","volume":"183","author":"HF G\u00fcnthard","year":"2001","journal-title":"J. Infect. Dis"},{"issue":"4","key":"pone.0296891.ref006","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.smim.2005.05.015","article-title":"Life cycle, migration and antigen presenting functions of spleen and lymph node dendritic cells: limitations of the Langerhans cells paradigm","volume":"17","author":"JA Villadangos","year":"2005","journal-title":"Semin Immunol"},{"issue":"11","key":"pone.0296891.ref007","doi-asserted-by":"crossref","first-page":"5548","DOI":"10.1128\/JVI.00124-08","article-title":"Characterization of the follicular dendritic cell reservoir of human immunodeficiency virus type 1","volume":"82","author":"BF Keele","year":"2008","journal-title":"J. Virol"},{"issue":"8","key":"pone.0296891.ref008","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/nm.1972","article-title":"HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation","volume":"15","author":"N Chomont","year":"2009","journal-title":"Nat. Med"},{"issue":"9","key":"pone.0296891.ref009","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1084\/jem.20092749","article-title":"Central nervous system (CNS)-resident natural killer cells suppress Th17 responses and CNS autoimmune pathology","volume":"207","author":"J Hao","year":"2010","journal-title":"J Exp Med"},{"issue":"8","key":"pone.0296891.ref010","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1111\/j.1582-4934.2011.01490.x","article-title":"Myelopoiesis in spleen-producing distinct dendritic-like cells","volume":"16","author":"JK Tan","year":"2012","journal-title":"J Cell Mol Med"},{"issue":"16","key":"pone.0296891.ref011","doi-asserted-by":"crossref","first-page":"9148","DOI":"10.1128\/JVI.01297-13","article-title":"High levels of CD2 expression identify HIV-1 latently infected resting memory CD4+ T cells in virally suppressed subjects","volume":"87","author":"M Iglesias-Ussel","year":"2013","journal-title":"J Virol"},{"issue":"4","key":"pone.0296891.ref012","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1615\/CritRevImmunol.2018026459","article-title":"Airway Macrophage and Dendritic Cell Subsets in the Resting Human Lung","volume":"38","author":"VI Patel","year":"2018","journal-title":"Crit Rev Immunol"},{"issue":"1","key":"pone.0296891.ref013","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.immuni.2018.12.027","article-title":"Plasmacytoid Dendritic Cells: Development, Regulation, and Function","volume":"50","author":"B. Reizis","year":"2019","journal-title":"Immunity"},{"issue":"5","key":"pone.0296891.ref014","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/imcb.12322","article-title":"A focus on natural killer T-cell subset characterization and developmental stages","volume":"98","author":"J Klibi","year":"2020","journal-title":"Immunol Cell Biol"},{"issue":"13","key":"pone.0296891.ref015","doi-asserted-by":"crossref","first-page":"6610","DOI":"10.1128\/JVI.00311-11","article-title":"Natural substrate concentrations can modulate the prophylactic efficacy of nucleotide HIV reverse transcriptase inhibitors","volume":"85","author":"JG Garc\u00eda-Lerma","year":"2011","journal-title":"J Virol"},{"key":"pone.0296891.ref016","doi-asserted-by":"crossref","first-page":"134475","DOI":"10.1016\/j.neulet.2019.134475","article-title":"Cell-type specific differences in antiretroviral penetration and the effects of HIV-1 Tat and morphine among primary human brain endothelial cells, astrocytes, pericytes, and microglia","volume":"712","author":"SH Patel","year":"2019","journal-title":"Neurosci Lett"},{"issue":"7","key":"pone.0296891.ref017","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1002\/jmv.21796","article-title":"Phylogeny and resistance profiles of HIV-1 POL sequences from rectal biopsies and blood","volume":"82","author":"TL Katzenstein","year":"2010","journal-title":"J. Med. Virol"},{"issue":"6","key":"pone.0296891.ref018","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1073\/pnas.1318249111","article-title":"Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues","volume":"111","author":"CV Fletcher","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"issue":"1","key":"pone.0296891.ref019","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1128\/JVI.74.1.139-145.2000","article-title":"Cellular compartments of human immunodeficiency virus type 1 replication in vivo: determination by presence of virion-associated host proteins and impact of opportunistic infection","volume":"74","author":"S. D Lawn","year":"2000","journal-title":"J. Virol"},{"key":"pone.0296891.ref020","first-page":"16","article-title":"Application of uMACS streptavidin microbeads for the analysis of HIV-1 directly from patient plasma","volume":"8","author":"D. Lupo","year":"2004","journal-title":"MACS& More"},{"issue":"3","key":"pone.0296891.ref021","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/jac\/dkf143","article-title":"HIV-1 in peripheral blood monocytes: an underrated viral source","volume":"50","author":"T. Zhu","year":"2002","journal-title":"J. Antimicrob. Chemother"},{"issue":"Pt 5","key":"pone.0296891.ref022","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1099\/0022-1317-76-5-1155","article-title":"CD4 expression on dendritic cells and their infection by human immunodeficiency virus","volume":"76","author":"S Patterson","year":"1995","journal-title":"J. Gen. Virol"},{"issue":"5320","key":"pone.0296891.ref023","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1126\/science.276.5320.1857","article-title":"Macrophages as a source of HIV during opportunistic infections","volume":"276","author":"J. M. Orenstein","year":"1997","journal-title":"Science"},{"issue":"1","key":"pone.0296891.ref024","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1172\/JCI114981","article-title":"Latent HIV-1 infection in enriched populations of blood monocytes and T cells from seropositive patients","volume":"87","author":"M. J McElrath","year":"1991","journal-title":"J. Clin. Invest"},{"issue":"10","key":"pone.0296891.ref025","doi-asserted-by":"crossref","first-page":"7015","DOI":"10.1073\/pnas.102672999","article-title":"Persistent HIV-1 infection of natural killer cells in patients receiving highly active antiretroviral therapy","volume":"99","author":"A Valentin","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"issue":"16","key":"pone.0296891.ref026","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1097\/01.aids.0000183125.93958.26","article-title":"Persistence of distinct HIV-1 populations in blood monocytes and naive and memory CD4 T cells during prolonged suppressive HAART","volume":"19","author":"P Delobel","year":"2005","journal-title":"AIDS"},{"issue":"1","key":"pone.0296891.ref027","first-page":"15","article-title":"Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissues facilitating infection of CD4+ T-helper cells","volume":"140","author":"H. Spiegel","year":"1992","journal-title":"Am. J. Pathol"},{"issue":"17","key":"pone.0296891.ref028","doi-asserted-by":"crossref","first-page":"9934","DOI":"10.1128\/JVI.00616-14","article-title":"CD4 ligation on human blood monocytes triggers macrophage differentiation and enhances HIV infection","volume":"88","author":"A Zhen","year":"2014","journal-title":"J Virol"},{"issue":"8417\u20138418","key":"pone.0296891.ref029","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1016\/S0140-6736(84)91666-0","article-title":"T4 positive human neoplastic cell lines susceptible to and permissive for HTLV-III","volume":"2","author":"M. Popovic","year":"1984","journal-title":"Lancet"},{"key":"pone.0296891.ref030","doi-asserted-by":"crossref","first-page":"422","DOI":"10.4049\/jimmunol.148.2.422","article-title":"Induction of IFN-a in peripheral blood mononuclear cells by HIV-infected monocytes","volume":"148","author":"HE Gendelman","year":"1992","journal-title":"J Immunol"},{"issue":"1","key":"pone.0296891.ref031","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1086\/430741","article-title":"Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated","volume":"192","author":"JA Johnson","year":"2005","journal-title":"J. Infect. Dis"},{"issue":"7","key":"pone.0296891.ref032","doi-asserted-by":"crossref","first-page":"e638","DOI":"10.1371\/journal.pone.0000638","article-title":"Simple PCR assays improve the sensitivity of HIV-1 subtype B drug resistance testing and allow linking of resistance mutations","volume":"2","author":"JA Johnson","year":"2007","journal-title":"PLoS One"},{"issue":"11","key":"pone.0296891.ref033","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1093\/infdis\/jiu333","article-title":"HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences","volume":"210","author":"JT Lipscomb","year":"2014","journal-title":"J Infect Dis"},{"key":"pone.0296891.ref034","first-page":"678","article-title":"Estimation of the number of nucleotide substitutions when there are strong transition-transversion and G + C-content biases","volume":"9","author":"K. Tamura","year":"1992","journal-title":"Molecular Biology and Evolution"},{"key":"pone.0296891.ref035","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1093\/molbev\/mst197","article-title":"MEGA6: Molecular Evolutionary Genetics Analysis version 6.0","volume":"30","author":"K Tamura","year":"2013","journal-title":"Molecular Biology and Evolution"},{"issue":"2","key":"pone.0296891.ref036","doi-asserted-by":"crossref","first-page":"vey030","DOI":"10.1093\/ve\/vey030","article-title":"Maintenance and reappearance of extremely divergent intra-host HIV-1 variants","volume":"4","author":"JO Wertheim","year":"2018","journal-title":"Virus Evol"},{"issue":"1","key":"pone.0296891.ref037","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/imm.12117","article-title":"Human dendritic cell subsets","volume":"140","author":"M Collin","year":"2013","journal-title":"Immunology"},{"key":"pone.0296891.ref038","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1002\/cyto.a.24027","article-title":"The Challenge of Distinguishing Cell\u2013Cell Complexes from Singlet Cells in Non-Imaging Flow Cytometry and Single-Cell Sorting","volume":"97A","author":"JG Burel","year":"2020","journal-title":"Cytometry Part A"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0296891","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T18:23:01Z","timestamp":1709058181000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0296891"}},"subtitle":[],"editor":[{"given":"Satish","family":"Rojekar","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,27]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0296891","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,27]]}}}