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Hematopoietic stem and progenitor cells (HSPCs) have been described as potential HIV-1 targets, but their roles as HIV-1 reservoirs remain controversial. Here we provide additional evidence for the susceptibility of several distinct HSPC subpopulations to HIV-1 infection in vitro and in vivo. In vitro infection experiments of HSPCs were performed with different HIV-1 Env-pseudotyped lentiviral particles and with replication-competent HIV-1. Low-level infection\/transduction of HSPCs, including hematopoietic stem cells (HSCs) and multipotent progenitors (MPP), was observed, preferentially via CXCR4, but also via CCR5-mediated entry. Multi-lineage colony formation in methylcellulose assays and repetitive replating of transduced cells provided functional proof of susceptibility of primitive HSPCs to HIV-1 infection. Further, the access to bone marrow samples from HIV-positive individuals facilitated the detection of HIV-1 gag cDNA copies in CD34+ cells from eight (out of eleven) individuals, with at least six of them infected with CCR5-tropic HIV-1 strains. In summary, our data confirm that primitive HSPC subpopulations are susceptible to CXCR4- and CCR5-mediated HIV-1 infection in vitro and in vivo, which qualifies these cells to contribute to the HIV-1 reservoir in patients.<\/jats:p>","DOI":"10.3390\/cells11192968","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T21:14:28Z","timestamp":1664140468000},"page":"2968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["HIV-1 Infection of Long-Lived Hematopoietic Precursors In Vitro and In Vivo"],"prefix":"10.3390","volume":"11","author":[{"given":"Sebastian","family":"Renelt","sequence":"first","affiliation":[{"name":"Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Schult-Dietrich","sequence":"additional","affiliation":[{"name":"Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0589-697X","authenticated-orcid":false,"given":"Hanna-Mari","family":"Baldauf","sequence":"additional","affiliation":[{"name":"Max von Pettenkofer Institute & Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU M\u00fcnchen, 81377 Munich, Germany"},{"name":"Institute of Medical Virology, Goethe University, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Stein","sequence":"additional","affiliation":[{"name":"Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit","family":"Kann","sequence":"additional","affiliation":[{"name":"Department of Medicine II\/Infectious Diseases, Goethe University Hospital, 60596 Frankfurt, Germany"},{"name":"Infektiologikum, Center for Infectious Diseases, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Bickel","sequence":"additional","affiliation":[{"name":"Infektiologikum, Center for Infectious Diseases, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrikke","family":"Kielland-Kaisen","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Medical School, Goethe University, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0088-2675","authenticated-orcid":false,"given":"Halvard","family":"Bonig","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-W\u00fcrttemberg-Hessen, Goethe University, 60528 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-3445","authenticated-orcid":false,"given":"Rolf","family":"Marschalek","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology, Goethe University, 60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-5872","authenticated-orcid":false,"given":"Michael A.","family":"Rieger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology\/Oncology, Goethe University Hospital, 60590 Frankfurt, Germany"},{"name":"German Cancer Consortium (DKTK), German Cancer Research Center, 69120 Heidelberg, Germany"},{"name":"Frankfurt Cancer Institute, 60596 Frankfurt, Germany"},{"name":"Cardio-Pulmonary Institute, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9569-9237","authenticated-orcid":false,"given":"Ralf","family":"Duerr","sequence":"additional","affiliation":[{"name":"Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany"},{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15109","DOI":"10.1073\/pnas.96.26.15109","article-title":"HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression","volume":"96","author":"Davey","year":"1999","journal-title":"Proc. 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