{
  "abstract": "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 ⁺ T cells by facilitating viral entry. HIV-1 infection upregulates both c-MET transcript abundance and receptor phosphorylation in primary CD4 ⁺ T cells. Genetic knockout, knockdown, or pharmacological inhibition of c-MET in CD4 ⁺ 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-κB, 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 ⁺ T cells and highlights HGF/c-MET signaling as a potential target for host-directed anti-HIV-1 therapeutic strategies.\n\nIMPORTANCE: 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 ⁺ 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-κB, 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shraddha Tripathi",
      "orcid": "0000-0002-2840-4061"
    },
    {
      "affs": [
        0
      ],
      "name": "Madeleine M. Allen"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Wu",
      "orcid": "0000-0002-5468-2487"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1mf6asrfgwbe8.bib",
  "cited_by": 0,
  "doi": "10.1128/mbio.02090-26",
  "fulltext_url": null,
  "id": "1mf6asrfgwbe8",
  "issns": [
    "2150-7511"
  ],
  "landing_url": "https://journals.asm.org/doi/10.1128/mbio.02090-26",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7221746636",
  "pdf_url": "https://journals.asm.org/doi/pdf/10.1128/mbio.02090-26",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-14",
  "publisher": "American Society for Microbiology",
  "ris": "https://research.draconitic.com/paper/1mf6asrfgwbe8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:28Z",
      "native_id": "10.1128/mbio.02090-26",
      "source": "crossref",
      "url": "https://journals.asm.org/doi/10.1128/mbio.02090-26"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2406|HIV Research and Treatment",
      "subfield": "microbiology"
    }
  ],
  "title": "HIV-1 hijacks HGF/c-MET signaling to promote viral entry and replication in primary CD4 ⁺ T cells",
  "title_text": "HIV-1 hijacks HGF/c-MET signaling to promote viral entry and replication in primary CD4 ⁺ T cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:28Z",
  "url": "https://research.draconitic.com/paper/1mf6asrfgwbe8",
  "venue": "mBio",
  "versions": []
}