{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:46:37Z","timestamp":1791985597850,"version":"4.4.0"},"reference-count":84,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R33AI169659, P30CA086862-25S"],"award-info":[{"award-number":["R33AI169659, P30CA086862-25S"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <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, but its role in HIV-1 infection has remained unclear. Here, we identify c-MET as a host factor that promotes HIV-1 replication in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells by facilitating viral entry. HIV-1 infection upregulates both c-MET transcript abundance and receptor phosphorylation in primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Genetic knockout, knockdown, or pharmacological inhibition of c-MET in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells markedly reduced HIV-1 Gag protein expression, viral production, and infectivity. Integrative analyses using RNA sequencing, flow cytometry, and HIV-1 infection and entry assays revealed that c-MET disruption decreased cell-surface expression of the HIV-1 receptor CD4 and the coreceptor CXCR4, thereby limiting viral entry and subsequent infection. In addition, c-MET disruption attenuated activation of NF-\u03baB, STAT1\/3, and MAPK signaling pathways, which are critical regulators of HIV-1 gene expression. Together, these findings demonstrate that HIV-1 exploits HGF\/c-MET signaling to coordinate entry receptor availability with intracellular signaling programs that support viral replication. Our study identifies a previously unrecognized host pathway required for efficient HIV-1 infection of primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and highlights HGF\/c-MET signaling as a potential target for host-directed anti-HIV-1 therapeutic strategies.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The hepatocyte growth factor (HGF)\/mesenchymal-epithelial transition factor (c-MET) signaling pathway is a well-established regulator of cell growth, survival, and migration and has been extensively studied as a therapeutic target in cancer. However, its role in HIV-1 infection has remained unknown. In this study, we found that c-MET enhances HIV-1 infection of primary CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cells by facilitating viral entry. We further demonstrate that HIV-1 replication enhances HGF-dependent c-MET phosphorylation, which is required for downstream signaling. Genetic ablation or pharmacologic inhibition of c-MET reduces HIV-1 entry by decreasing expression of viral entry receptors. Moreover, c-MET inhibition or knockout disrupts activation of cellular signaling pathways, including NF-\u03baB, JAK\/STAT, and p38 MAPK. These findings reveal a previously unrecognized role for HGF\/c-MET signaling in HIV-1 pathogenesis and suggest that targeting c-MET may represent a novel host-directed strategy for HIV-1 intervention.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02090-26","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:01:02Z","timestamp":1791982862000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","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":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2840-4061","authenticated-orcid":true,"given":"Shraddha","family":"Tripathi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine M.","family":"Allen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-2487","authenticated-orcid":true,"given":"Li","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00452-3"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2025.08.004"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/312763a0"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.70.9.6288-6295.1996"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.10.1793"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2018.03.003"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2026.03.046"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1846706"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3205"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-025-02033-1"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90363-4"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.16.7001"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6041890"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90318-2"},{"key":"e_1_3_6_16_2","first-page":"2019","article-title":"Autophosphorylation modulates the kinase activity and oncogenic potential of the Met receptor tyrosine kinase","volume":"9","author":"Rodrigues GA","year":"1994","unstructured":"Rodrigues GA, Park M. 1994. 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