{
  "abstract": "The low-density lipoprotein receptor (LDLR) is a major cellular receptor for vesicular stomatitis virus glycoprotein (VSV-G), which is widely used to pseudotyped virus vectors. A replication incompetent VSV-G-pseudotyped HIV (VSV-G-HIVLuc) has been used in HIV infection studies. Although IL-27-polarized macrophages induce multiple antiviral genes and resist replication-competent HIV infection, their impact on VSV-GHIVLuc infection has not been studied. Here, we evaluated the role of IL-27 polarization on VSV-G-HIVLuc infection. Infection was monitored by luciferase activity. Cell-surface LDLR was analyzed by flow cytometry. LDLR transcripts and protein expression were quantified by qRT-PCR and Western blotting, respectively. Viral binding was assessed by measuring cell-associated p24 antigen, while post-entry events were evaluated by quantifying late reverse-transcription products. VSV-G-HIVLuc infection in IL-27-polarized M-CSF-induced macrophages (27M-Mac) and IL-27-polarized GM-CSFinduced macrophages (27GM-Mac) was reduced to 5.8{+/-}0.4% and 5.9{+/-}2.1%, respectively (both p<0.0001), compared to unpolarized macrophages. 27M-Mac and 27GM-Mac reduced cell-surface LDLR to 38.3{+/-}2.6% (p<0.01) and 31.4{+/-}3.2% (p<0.01). Western blotting showed that total LDLR protein decreased to 48{+/-}0.8% in 27M-Mac (p<0.01), whereas 27GM-Mac showed no significant change. However, LDLR transcripts increased approximately 1.6-1.9-fold following IL-27 treatment in both macrophage types (p<0.01). Viral binding to 27M-Mac decreased modestly, while binding to 27GM-Mac decreased significantly to 67.5 {+/-} 7.5% of that to GM-Mac (p<0.05, n=3). In contrast, late reverse-transcription products decreased to 23{+/-}2.1% (p<0.0001) and 44{+/-}1.5% (p<0.0001). These findings demonstrate that IL-27 downregulates cell-surface LDLR expression in macrophages despite increasing LDLR transcript abundance, suggesting that IL-27 restricts VSV-G-pseudotyped Lentiviral infection through both receptor-associated and additional post-entry mechanisms.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Qian Chen"
    },
    {
      "name": "Udeshika Kariyawasam"
    },
    {
      "name": "Mayra Maruquez"
    },
    {
      "name": "Jordan Metz"
    },
    {
      "name": "Jun Yang"
    },
    {
      "name": "Adam Rupert"
    },
    {
      "name": "Tomozumi Imamichi",
      "orcid": "0009-0007-0910-5297"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dsanrdm0fbt9z.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.761012",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761012v1.full",
  "id": "dsanrdm0fbt9z",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761012v1",
  "language": "en",
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7223989612",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761012v1.full.pdf",
  "pmcid": "PMC13733686",
  "pmid": "42990135",
  "published": "2026-10-22",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/dsanrdm0fbt9z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:54Z",
      "native_id": "10.64898/2026.10.22.761012",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761012v2"
    },
    {
      "first_seen": "2026-11-08T12:23:24Z",
      "native_id": "PMC13733686",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.22.761012"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "IL-27 Reduces Cell-Surface LDLR in Human Macrophages and Restricts VSV-G-Pseudotyped HIV infection",
  "title_text": "IL-27 Reduces Cell-Surface LDLR in Human Macrophages and Restricts VSV-G-Pseudotyped HIV infection",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:24Z",
  "url": "https://research.draconitic.com/paper/dsanrdm0fbt9z",
  "venue": "bioRxiv",
  "versions": []
}