Viral immune profiles in multiple sclerosis and HIV co-infection providing insights into antiretroviral treatment-associated immuno-remodeling

Multiple sclerosis (MS) and human immunodeficiency virus (HIV) rarely co-occur, suggesting HIV-mediated modulation of MS-related viral immunopathology. This multicentre cross-sectional study analyzed 14 individuals with MS + HIV (HIV → MS, n = 4; MS → HIV, n = 10), alongside HIV-positive individuals on antiretroviral therapy (ART, n = 21), MS ( n = 21; 18 on disease-modifying therapies DMTs), and healthy controls ( n = 21). IgG/IgM responses to Epstein–Barr virus (EBV), Cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and human endogenous retrovirus-W envelope (HERV-W env) were quantified by ELISA. HERV-W env expression in PBMC subsets was assessed by FACS/qPCR and flow cytometry (monoclonal antibody CALI222B). Discriminant function analysis (DFA) was used to evaluate a preliminary cohort classification. MS + HIV cohorts displayed higher CMV IgG seroprevalence (95–100% vs. 45% in MS; OR 24.4) and titres. EBNA-1 IgG prevailed in MS and MS + HIV (95–100% vs. 67% in HIV). HERV-W expression was reduced in HIV versus MS, particularly in HIV → MS. Exploratory DFA classified cohorts with 79.6% accuracy (CMV/EBNA-1 primary discriminators). Stepwise analysis identified CMV, EBNA-1, and EBV VCA IgG as main predictors, achieving 100% classification accuracy for MS + HIV (76.4% overall). CMV-dominated profiles distinguish MS + HIV comorbidity, with HIV/ART-associated suppression of EBV/HHV-6 humoral responses and HERV-W gene expression, suggesting an immune remodeling that may explain reduced MS prevalence among people living with HIV.

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Journal
Scientific Reports
Published
2026-10-09
DOI
https://doi.org/10.1038/s41598-026-75189-6
Primary Topic
HIV Research and Treatment
Type
article
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article

Viral immune profiles in multiple sclerosis and HIV co-infection providing insights into antiretroviral treatment-associated immuno-remodeling

María Inmaculada Domínguez‐Mozo, Dulcenombre Gómez‐Garré, Vicente Estrada, Juncal Pérez-Somarriba Moreno et al.
Scientific Reports
HIV Research and Treatment
article

Viral immune profiles in multiple sclerosis and HIV co-infection providing insights into antiretroviral treatment-associated immuno-remodeling

María Inmaculada Domínguez‐Mozo, Dulcenombre Gómez‐Garré, Vicente Estrada, Juncal Pérez-Somarriba Moreno, José Rodríguez, Roberto Álvarez‐Lafuente, Noemí Cabello‐Clotet, Maria Ángel García‐Martínez, Jorge Millán‐Pascual, Adriana Ortega‐Hernández, Virginia Meca‐Lallana, Stefano Ruberto, Javier Rodríguez-Añover, Yolanda Blanco, Hugo Martín-García, Rafael Arroyo, Carmen Muñoz-Fernández, Carolina Olmos‐Mata, Iván Pérez-Gutiérrez, Andrea Alonso-Garrido, Guadalupe Pérez de Villar, Yolanda Aladro, Ana López-Real, Francisco J. Valenzuela-Rojas, Lucienne C. Frossard-França, María L. Martínez-Ginés, Jose Reynaldo Homen, Melanie Rojas-Salazar, María Núñez-Orantos
article en

Abstract

Multiple sclerosis (MS) and human immunodeficiency virus (HIV) rarely co-occur, suggesting HIV-mediated modulation of MS-related viral immunopathology. This multicentre cross-sectional study analyzed 14 individuals with MS + HIV (HIV → MS, n = 4; MS → HIV, n = 10), alongside HIV-positive individuals on antiretroviral therapy (ART, n = 21), MS ( n = 21; 18 on disease-modifying therapies DMTs), and healthy controls ( n = 21). IgG/IgM responses to Epstein–Barr virus (EBV), Cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and human endogenous retrovirus-W envelope (HERV-W env) were quantified by ELISA. HERV-W env expression in PBMC subsets was assessed by FACS/qPCR and flow cytometry (monoclonal antibody CALI222B). Discriminant function analysis (DFA) was used to evaluate a preliminary cohort classification. MS + HIV cohorts displayed higher CMV IgG seroprevalence (95–100% vs. 45% in MS; OR 24.4) and titres. EBNA-1 IgG prevailed in MS and MS + HIV (95–100% vs. 67% in HIV). HERV-W expression was reduced in HIV versus MS, particularly in HIV → MS. Exploratory DFA classified cohorts with 79.6% accuracy (CMV/EBNA-1 primary discriminators). Stepwise analysis identified CMV, EBNA-1, and EBV VCA IgG as main predictors, achieving 100% classification accuracy for MS + HIV (76.4% overall). CMV-dominated profiles distinguish MS + HIV comorbidity, with HIV/ART-associated suppression of EBV/HHV-6 humoral responses and HERV-W gene expression, suggesting an immune remodeling that may explain reduced MS prevalence among people living with HIV.

Scientific Reports
Instituto de Salud Carlos III (ES), Hospital General Universitario Gregorio Marañón (ES), Hospital Clínico San Carlos (ES), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES), Hospital Universitario de Gran Canaria Doctor Negrín (ES), Hospital Universitario de Getafe (ES), Hospital Universitario Quirónsalud Madrid (ES), Hospital Clínic de Barcelona (ES), Hospital Universitario de La Princesa (ES), Hospital Del Mar (ES), Complexo Hospitalario Universitario A Coruña (ES), Hospital Universitario Virgen de la Arrixaca (ES), Complejo Hospitalario Torrecárdenas (ES), Hospital Universitario Ramón y Cajal (ES), Hospital Central de la Defensa Gómez Ulla (ES)
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