Beyond COVID-19 in people with HIV: Specific miRNA expression profile persist after SARS-CoV-2 clearance
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The impact of SARS-CoV-2 on epigenetic regulation in people with HIV (PWHIV) is not well understood. MicroRNAs, key post-transcriptional regulators, may serve as biomarkers of disease. This study aimed to identify plasma miRNAs reflecting epigenetic changes in PWHIV after SARS-CoV-2 resolution. METHODS: We sequenced plasma smallRNA from 20 PWHIV at a median of 10 weeks after SARS-CoV-2 infection, and 18 SARS-CoV-2 uninfected and unvaccinated PWHIV. MirDeep2 was used for miRNA identification, and significant differential expression (SDE) and classification performance were calculated using GLMs and PLS-DA. Correlations were performed using spearman test. Target enrichment was analyzed using miRTarbase, RNAInter, and KEGG databases, and tissue expression was analysed using the IMOTA database. RESULTS: Thirty-five microRNAs were SDE between groups. Hsa-mir-181a-2-3p was correlated to time elapsed since SARS-CoV-2 infection and sampling. Functional enrichment analysis predicted 410 target genes, which in turn overrepresented 52 cellular pathways, mainly related to neurodegeneration, major signaling cascades, and oncologic and cardiovascular diseases. The most significant pathways were Huntington's disease and PI3K-Akt signalling pathway, while those with the highest number of targeted genes were Pathways of neurodegeneration and Alzheimer's disease. The hsa-miR-374b-5p showed excellent predictive ability in classifying the SARS-CoV-2 infection status in more than 93 % of all instances. CONCLUSION: SARS-CoV-2 infection in PWHIV leaves an epigenetic signature of 35 SDE microRNAs, with hsa-miR-374b-5p as a strong post-infection marker. These microRNAs regulate genes mainly involved in neurodegenerative, cardiovascular, and oncologic processes, potentially underlying post-COVID symptomatology.
Authors: Sergio Grande-García, Manuel Llamas-Adán, Celia Crespo-Bermejo, Violeta Lara-Aguilar, Sonia Arca-Lafuente, Luz Martín-Carbonero, Pablo Ryan, Ignacio de los Santos, María de Lagarde, Rafael Mican-Rivera, Santiago Moreno, Salvador Resino, Juan Berenguer, Verónica Briz, Amanda Fernández-Rodríguez
Institutions: Instituto de Salud Carlos III, Centro Nacional de Microbiologia, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research, Hospital Universitario Infanta Leonor, Hospital Universitario de La Princesa, Universidad Complutense de Madrid, Research Institute Hospital 12 de Octubre, Hospital Universitario 12 De Octubre, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,310
Funders: Centro de Investigación Biotecnológica en Red de Enfermedades Infecciosas, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades, European Commission, Ministerio de Ciencia e Innovación, Centro de Investigación Biomédica en Red de Cáncer, Instituto de Salud Carlos III, European Regional Development Fund, Center for International Business Education and Research, University of Illinois at Urbana-Champaign
Awards: G2409368043, G2901506311, Estudio del reservorio VIH en sangre periférica y su relación con la infección por VHC, sistema inmune y perfil de microARNs, G5064538422, G5587507405, G5720501267, G6332176011, Impacto de la erradicación y aclaramiento del VHC con los nuevos antivirales de acción directa, en pacientes coinfectados VIH/VHC en el reservorio VIH en sangre periférica y sistema inmune., G7448429358, G7780475403, G7851644996, G8270641673, G8910888795
OpenAlex ID: W4417299121