{
  "abstract": "HIV-1 and HIV-2 share transmission and replication characteristics, but require clinical differentiation. HIV-2 exhibits lower viral loads and slower disease progression, and most patients remain long-term non-progressors. Differentiation is crucial for selecting appropriate viral load monitoring tests and avoiding ineffective antiretroviral treatments, particularly non-nucleoside reverse transcriptase inhibitors, and certain protease inhibitors that do not work against HIV-2. Increased PrEP use may result in new infections testing negative for viral markers. This study aims to identify circulating tRNA expression profiles that could serve as non-viral biomarkers to detect and differentiate HIV-2 from HIV-1 infections. An initial pilot study analyzed 88 tRNAs in plasma samples from HIV-1- (n = 4) and HIV-2 (n = 4)-infected individuals, plus four healthy controls, using a tRNA-based PCR array for target identification. Eighteen selected tRNAs were further analyzed in a larger independent group of samples: HIV-1 (n = 20), HIV-2 (n = 20), and healthy controls (n = 20) for independent verification. A plasma tRNA diagnostic model was developed from these results and evaluated in 24 independent samples to detect and differentiate HIV-2 from HIV-1 infection. We identified a tRNA-based model (Model-II) containing six differentially expressed tRNAs (Leu-TAA, mt-Asp-GTC, mt-Ala-TGC, mt-Lys-TTT, mt-LeuT-AA, and Gly-CCC-1) that could detect HIV-2 infection and distinguish it from HIV-1 infection and healthy controls with 100% accuracy, sensitivity, and specificity. We also found that other blood-borne viruses such as HTLV, HBV, and HCV had no cross-reactivity with HIV-2, demonstrating that Model-II is specific for HIV-2 infection. This study establishes proof of concept for tRNA expression profiles as HIV diagnostic biomarkers. The tRNA-based Model-II represents a promising diagnostic tool for identifying HIV-2 infection and differentiating it from HIV-1.\n\nIMPORTANCE: HIV-2 infection requires accurate differentiation from HIV-1 to guide appropriate antiretroviral therapy, as HIV-2 exhibits intrinsic resistance to non-nucleoside reverse transcriptase inhibitors and certain protease inhibitors. Current diagnostic challenges include the absence of FDA-approved HIV-2 RNA quantification assays and potential false-negative results in LEVI (low-level viremia with evolving viral infection) syndrome patients on pre-exposure prophylaxis (PrEP), in whom viral markers may be undetectable. We developed a novel diagnostic approach using circulating transfer RNA (tRNA) expression profiles as host-derived, non-viral biomarkers. Our six-tRNA panel (Model-II) achieved 100% accuracy, sensitivity, and specificity in detecting HIV-2 infection while distinguishing it from HIV-1 and other blood-borne viral infections (HTLV, HBV, and HCV). This represents the first tRNA-based diagnostic model for HIV, offering a promising complementary tool for early detection and accurate viral differentiation, particularly in clinical scenarios where traditional viral markers are absent or unreliable.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Santanu Biswas",
      "orcid": "0000-0003-4056-4305"
    },
    {
      "affs": [
        0
      ],
      "name": "David R. McGivern",
      "orcid": "0000-0003-3497-5087"
    },
    {
      "affs": [
        0
      ],
      "name": "Indira K. Hewlett"
    },
    {
      "affs": [
        0
      ],
      "name": "Krishnakumar Devadas",
      "orcid": "0000-0003-2658-1264"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0zz6qhy3svgfv.bib",
  "cited_by": 0,
  "doi": "10.1128/jcm.00378-26",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712997/",
  "id": "0zz6qhy3svgfv",
  "issns": [
    "0095-1137",
    "1098-660X"
  ],
  "landing_url": "https://doi.org/10.1128/jcm.00378-26",
  "language": "en",
  "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": [
    [
      "heading",
      "Innovative Diagnostic Methods"
    ],
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7204814093",
  "pdf_url": "https://journals.asm.org/doi/pdf/10.1128/jcm.00378-26?download=true",
  "pmcid": "PMC13712997",
  "pmid": "42671187",
  "published": "2026-08-31",
  "publisher": "American Society for Microbiology (ASM)",
  "ris": "https://research.draconitic.com/paper/0zz6qhy3svgfv.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:28Z",
      "native_id": "PMC13712997",
      "source": "pmc",
      "url": "https://doi.org/10.1128/jcm.00378-26"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2406|HIV Research and Treatment",
      "subfield": "microbiology"
    }
  ],
  "title": "A novel biomarker signature based on circulating transfer RNA (tRNA) can detect and differentiate HIV-2 infection from HIV-1",
  "title_text": "A novel biomarker signature based on circulating transfer RNA (tRNA) can detect and differentiate HIV-2 infection from HIV-1",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:28Z",
  "url": "https://research.draconitic.com/paper/0zz6qhy3svgfv",
  "venue": "Journal of Clinical Microbiology",
  "versions": []
}