{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:36:57Z","timestamp":1786117017165,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,4]]},"group-title":"Microbiology","reference-count":84,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R33AI169659 and P30CA086862-25S"],"award-info":[{"award-number":["R33AI169659 and P30CA086862-25S"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The mesenchymal-epithelial transition factor (c-MET) is a receptor tyrosine kinase best known for mediating hepatocyte growth factor (HGF) signaling in cancer, yet its role in HIV-1 infection remains undefined. Here we identify c-MET as a host factor that facilitates HIV-1 replication in CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells by promoting viral entry. HIV-1 infection upregulates c-MET transcripts and phosphorylation in primary CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells. Knockout or pharmacological inhibition of c-MET in CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells significantly reduces HIV-1 Gag expression, viral production, and infectivity. Mechanistically, c-MET disruption reduces cell-surface expression of the HIV-1 receptor CD4 and the coreceptor CXCR4, thereby restricting viral entry and infection. Furthermore, c-MET disruption diminishes activation of NF-\u03baB, STAT1\/3, and MAPK signaling pathways that are critical for HIV-1 gene expression. These findings reveal that HIV-1 exploits HGF\/c-MET signaling to coordinate entry receptor availability and intracellular signaling, uncovering a previously unrecognized host pathway that supports viral replication in CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells. Overall, our results highlight an essential role for HGF\/c-MET signaling in HIV-1 infection of primary CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells and suggest a potential host-directed therapeutic target.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        c-MET facilitates HIV-1 replication in CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cells by promoting viral entry\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        HIV-1 infection upregulates c-MET transcripts and phosphorylation in CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cells\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        c-MET disruption reduces CD4 and CXCR4 expression on CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cell surfaces\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>c-MET disruption diminishes activation of cellular pathways important for HIV-1<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.03.742552","type":"posted-content","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:50:38Z","timestamp":1785909038000},"source":"Crossref","is-referenced-by-count":0,"title":["HIV-1 Hijacks HGF\/c-MET Signaling to Promote Viral Entry and Replication in Primary CD4\n                  <sup>+<\/sup>\n                  T Cells"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2840-4061","authenticated-orcid":false,"given":"Shraddha","family":"Tripathi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine M.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-2487","authenticated-orcid":false,"given":"Li","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026080606050996000_2026.08.03.742552v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00452-3"},{"key":"2026080606050996000_2026.08.03.742552v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2025.08.004"},{"key":"2026080606050996000_2026.08.03.742552v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/312763a0"},{"key":"2026080606050996000_2026.08.03.742552v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.70.9.6288-6295.1996"},{"key":"2026080606050996000_2026.08.03.742552v1.5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.10.1793"},{"key":"2026080606050996000_2026.08.03.742552v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2018.03.003"},{"key":"2026080606050996000_2026.08.03.742552v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2026.03.046"},{"key":"2026080606050996000_2026.08.03.742552v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1846706"},{"key":"2026080606050996000_2026.08.03.742552v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3205"},{"key":"2026080606050996000_2026.08.03.742552v1.10","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-025-02033-1"},{"key":"2026080606050996000_2026.08.03.742552v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90363-4"},{"key":"2026080606050996000_2026.08.03.742552v1.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.16.7001"},{"key":"2026080606050996000_2026.08.03.742552v1.13","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6041890"},{"key":"2026080606050996000_2026.08.03.742552v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90318-2"},{"key":"2026080606050996000_2026.08.03.742552v1.15","first-page":"2019","article-title":"Autophosphorylation modulates the kinase activity and oncogenic potential of the Met receptor tyrosine kinase","volume":"9","year":"1994","journal-title":"Oncogene"},{"key":"2026080606050996000_2026.08.03.742552v1.16","first-page":"1631","article-title":"The motogenic and mitogenic responses to HGF are amplified by the Shc adaptor protein","volume":"10","year":"1995","journal-title":"Oncogene"},{"key":"2026080606050996000_2026.08.03.742552v1.17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.36.22913"},{"key":"2026080606050996000_2026.08.03.742552v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.07.048"},{"key":"2026080606050996000_2026.08.03.742552v1.19","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2015.3943"},{"key":"2026080606050996000_2026.08.03.742552v1.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-022-02179-2"},{"key":"2026080606050996000_2026.08.03.742552v1.21","first-page":"4277","article-title":"Scatter factor\/hepatocyte growth factor protects against cytotoxic death in human glioblastoma via phosphatidylinositol 3-kinase- and AKT-dependent pathways","volume":"60","year":"2000","journal-title":"Cancer Res"},{"key":"2026080606050996000_2026.08.03.742552v1.22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-1929"},{"key":"2026080606050996000_2026.08.03.742552v1.23","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-30-96"},{"key":"2026080606050996000_2026.08.03.742552v1.24","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-180"},{"key":"2026080606050996000_2026.08.03.742552v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3012"},{"key":"2026080606050996000_2026.08.03.742552v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1261"},{"key":"2026080606050996000_2026.08.03.742552v1.27","doi-asserted-by":"publisher","DOI":"10.1177\/1758834011422556"},{"key":"2026080606050996000_2026.08.03.742552v1.28","doi-asserted-by":"publisher","DOI":"10.1089\/AID.2024.0003"},{"key":"2026080606050996000_2026.08.03.742552v1.29","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-026-15874-x"},{"key":"2026080606050996000_2026.08.03.742552v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2019.05.036"},{"key":"2026080606050996000_2026.08.03.742552v1.31","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.4.2855-2864.1998"},{"key":"2026080606050996000_2026.08.03.742552v1.32","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.18.8358-8367.2000"},{"key":"2026080606050996000_2026.08.03.742552v1.33","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1006448"},{"key":"2026080606050996000_2026.08.03.742552v1.34","doi-asserted-by":"publisher","DOI":"10.1021\/jm2007613"},{"key":"2026080606050996000_2026.08.03.742552v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70344-3"},{"key":"2026080606050996000_2026.08.03.742552v1.36","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/BF03401812","article-title":"The critical role of p38 MAP kinase in T cell HIV-1 replication","volume":"3","year":"1997","journal-title":"Mol Med"},{"key":"2026080606050996000_2026.08.03.742552v1.37","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200403260-00004"},{"key":"2026080606050996000_2026.08.03.742552v1.38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-091207"},{"key":"2026080606050996000_2026.08.03.742552v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2013.01.020"},{"key":"2026080606050996000_2026.08.03.742552v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.103159"},{"key":"2026080606050996000_2026.08.03.742552v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103588"},{"key":"2026080606050996000_2026.08.03.742552v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1193-8"},{"key":"2026080606050996000_2026.08.03.742552v1.43","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.4.1060-1072.2002"},{"key":"2026080606050996000_2026.08.03.742552v1.44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004875"},{"key":"2026080606050996000_2026.08.03.742552v1.45","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.8.7080-7086.1999"},{"key":"2026080606050996000_2026.08.03.742552v1.46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407477200"},{"key":"2026080606050996000_2026.08.03.742552v1.47","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07141.x"},{"key":"2026080606050996000_2026.08.03.742552v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.12.005"},{"key":"2026080606050996000_2026.08.03.742552v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2013.06.006"},{"key":"2026080606050996000_2026.08.03.742552v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0922-1"},{"key":"2026080606050996000_2026.08.03.742552v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0315-3"},{"key":"2026080606050996000_2026.08.03.742552v1.52","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-02055-w"},{"key":"2026080606050996000_2026.08.03.742552v1.53","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-3541"},{"key":"2026080606050996000_2026.08.03.742552v1.54","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01970-06"},{"key":"2026080606050996000_2026.08.03.742552v1.55","doi-asserted-by":"publisher","DOI":"10.4321\/s1130-01082010000600004"},{"key":"2026080606050996000_2026.08.03.742552v1.56","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i12.1854"},{"key":"2026080606050996000_2026.08.03.742552v1.57","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-11-74"},{"key":"2026080606050996000_2026.08.03.742552v1.58","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.5.7582299"},{"key":"2026080606050996000_2026.08.03.742552v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25191-5"},{"key":"2026080606050996000_2026.08.03.742552v1.60","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1651730"},{"key":"2026080606050996000_2026.08.03.742552v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116477"},{"key":"2026080606050996000_2026.08.03.742552v1.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2026.109451"},{"key":"2026080606050996000_2026.08.03.742552v1.63","doi-asserted-by":"publisher","DOI":"10.1002\/ccs3.70075"},{"key":"2026080606050996000_2026.08.03.742552v1.64","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2307318120"},{"key":"2026080606050996000_2026.08.03.742552v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30879-3"},{"key":"2026080606050996000_2026.08.03.742552v1.66","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.1.609-614.2005"},{"key":"2026080606050996000_2026.08.03.742552v1.67","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2010.075"},{"key":"2026080606050996000_2026.08.03.742552v1.68","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2011.0100"},{"key":"2026080606050996000_2026.08.03.742552v1.69","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-07-658823"},{"key":"2026080606050996000_2026.08.03.742552v1.70","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15444"},{"key":"2026080606050996000_2026.08.03.742552v1.71","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.139"},{"key":"2026080606050996000_2026.08.03.742552v1.72","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401666"},{"key":"2026080606050996000_2026.08.03.742552v1.73","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00721-9"},{"key":"2026080606050996000_2026.08.03.742552v1.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.05.014"},{"key":"2026080606050996000_2026.08.03.742552v1.75","doi-asserted-by":"publisher","DOI":"10.1002\/ana.78035"},{"key":"2026080606050996000_2026.08.03.742552v1.76","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029124"},{"key":"2026080606050996000_2026.08.03.742552v1.77","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-010-0111-2"},{"key":"2026080606050996000_2026.08.03.742552v1.78","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-07-0054"},{"key":"2026080606050996000_2026.08.03.742552v1.79","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01536-25"},{"key":"2026080606050996000_2026.08.03.742552v1.80","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.005608"},{"key":"2026080606050996000_2026.08.03.742552v1.81","doi-asserted-by":"publisher","DOI":"10.1002\/0471143030.cb2605s43"},{"key":"2026080606050996000_2026.08.03.742552v1.82","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104750"},{"key":"2026080606050996000_2026.08.03.742552v1.83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034521"},{"key":"2026080606050996000_2026.08.03.742552v1.84","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0069-7"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.08.03.742552","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T13:05:22Z","timestamp":1786021522000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.08.03.742552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":84,"URL":"https:\/\/doi.org\/10.64898\/2026.08.03.742552","relation":{},"subject":[],"published":{"date-parts":[[2026,8,4]]},"subtype":"preprint"}}