Abstract
While systemic immune dysregulation is well-documented in HIV infection, its impact on blood and respiratory tract viromes remains poorly understood. This study characterizes HIV-associated alterations in viral communities and examines their clinical relevance. Using viral metagenomics, we compare 203 ART-treated HIV-positive individuals and 120 healthy controls. HIV infection significantly restructures the blood virome, shifting from bacteriophage dominance (96.2% in controls) to eukaryotic virus predominance (69.1%). Increased alpha diversity, significant β-diversity divergence, and heightened dispersion heterogeneity are observed in HIV cases. Consistent enrichment of Flaviviridae, Parvoviridae, and Anelloviridae is detected. Throat viromes maintain phage dominance (>90%) but exhibit strain-level diversification, including Microviridae proliferation. Network analysis reveals Retroviridae-Anelloviridae co-dynamics (r = +0.562) and identifies Picobirnaviridae as a key interactor. Functional analysis shows enriched viral replication and host modulation genes. Compartment-specific disruption patterns nominate Pegivirus C, parvovirus B19, and Anelloviruses as potential biomarkers. Cross-kingdom viral interactions suggest novel mechanisms influencing disease progression and support future virome-targeting adjunct therapies.
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Acknowledgements
We extend our gratitude to Dr. Ding Mingdong, Director of the Department of Infectious Diseases at Taizhou People’s Hospital Affiliated to Nanjing Medical University, for providing the clinical medical records for this study. This study was supported by the National Key R&D Program of China (2024YFA1803100), National Natural Science Foundation of China (no. 82550118), the Key Research Project of Taizhou Clinical Medical College, Nanjing Medical University (grant no. TZKY20230305), Research Projects on Experimental Technologies for Large-Scale Scientific Instruments of Fudan University (DXYQ2025080), the Shanghai Science and Technology Innovation Action Plan (grant no. 24142202800), Open Project of the Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) at Fudan University (FDMV-2026003), Taizhou City “311 Project” Training Recipient Scientific Research Funding Program (no. 9), the Shanghai Municipal Science and Technology Major Project (ZD2021CY001) and the National Key Project for Infectious Diseases of China (2025ZD01905703). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Li, W., Ni, P., Xu, J. et al. HIV-driven virome dysbiosis unveils distinct virome features and inter-viral correlations in blood and respiratory niches. Commun Biol (2026). https://doi.org/10.1038/s42003-026-10221-z
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DOI: https://doi.org/10.1038/s42003-026-10221-z
