{
  "abstract": "HIV-1 persists across multiple anatomical compartments, yet the mutational processes shaping viral diversity within these reservoirs remain incompletely understood. We investigated HIV-1 mutational signatures across blood, spleen, gut, and brain tissues from 21 people with HIV enrolled in the Last Gift rapid autopsy program. Mutations in single-genome HIV-1 env DNA sequences were quantified by trinucleotide context and deconvolved using non-negative matrix factorization. Two APOBEC3-associated signatures were resolved and together accounted for approximately 50% of all mutations; this contribution remained stable after normalization by the number of potential APOBEC3 target sites. Normalization further revealed a minor signature consistent with methylation-induced cytosine deamination. Mutational patterns were driven primarily by donor identity rather than anatomical compartment. Identical APOBEC3-hypermutated sequences were recovered across brain, gut, and blood, consistent with clonal expansion and trafficking of infected cells. These findings establish APOBEC3 activity as a major contributor to HIV-1 mutagenesis across tissue reservoirs and demonstrate that APOBEC3-associated mutagenesis is strongly donor-specific.",
  "abstract_shown": true,
  "affiliations": [
    "Texas Biomedical Research Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "M. Soleimanpour"
    },
    {
      "name": "N. Haghjoo"
    },
    {
      "name": "J. lehle"
    },
    {
      "name": "R. Springman-Rodriguez"
    },
    {
      "name": "D. M. Smith"
    },
    {
      "name": "S. Gianella Weibel"
    },
    {
      "name": "A. Chaillon"
    },
    {
      "affs": [
        0
      ],
      "name": "D. Ebrahimi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d15d7e6ymrdbw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.23.753842",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753842v1.full",
  "id": "d15d7e6ymrdbw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753842v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ],
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7214323481",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753842v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d15d7e6ymrdbw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:37Z",
      "native_id": "10.64898/2026.09.23.753842",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753842v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Deconvolution of HIV-1 Mutational Signatures Reveals Dominant and Donor-Specific APOBEC3-Associated Mutagenesis Across Anatomical Compartments",
  "title_text": "Deconvolution of HIV-1 Mutational Signatures Reveals Dominant and Donor-Specific APOBEC3-Associated Mutagenesis Across Anatomical Compartments",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:37Z",
  "url": "https://research.draconitic.com/paper/d15d7e6ymrdbw",
  "venue": "bioRxiv",
  "versions": []
}