Cytomegalovirus, Epstein-Barr Virus, Herpes Simplex Virus, and Varicella Zoster Virus Infection Dynamics in People with Multiple Sclerosis from Northern Italy

Maple, Peter A.; Tanasescu, Radu; Constantinescu, Cris S.; Valentino, Paola; Capobianco, Marco; D’Orso, Silvia; Borsellino, Giovanna; Battistini, Luca; Ristori, Giovanni; Mechelli, Rosella; Salvetti, Marco; Gran, Bruno

Abstract

Previous exposure to Epstein–Barr virus (EBV) is strongly associated with the development of multiple sclerosis (MS). By contrast, past cytomegalovirus (CMV) infection may have no association, or be negatively associated with MS. This study aimed to investigate the associations of herpesvirus infections with MS in an Italian population. Serum samples (n = 200) from Italian people with multiple sclerosis (PwMS) classified as the relapsing-and-remitting clinical phenotype and (n = 137) healthy controls (HCs) were obtained from the CRESM Biobank, Orbassano, Italy. Both PwMS and HCs samples were selected according to age group (20–39 years, and 40 or more years) and sex. EBV virus capsid antigen (VCA) IgG, EBV nucleic acid-1 antigen (EBNA-1) IgG, CMV IgG, herpes simplex virus (HSV) IgG, and varicella zoster virus (VZV) IgG testing was undertaken using commercial ELISAs. EBV VCA IgG and EBNA-1 IgG seroprevalences were 100% in PwMS and 93.4% and 92.4%, respectively, in HCs. EBV VCA IgG and EBNA-1 IgG levels were higher (p < 0.001) in PwMS compared with HCs. For PwMS, the EBNA-1 IgG levels decreased with age, particularly in females. The CMV IgG seroprevalence was 58.7% in PwMS and 62.9% in HCs. CMV IgG seroprevalence increased with age. The HSV IgG seroprevalence was 71.2% in PwMS and 70.8% in HCs. HSV IgG levels were lower (p = 0.0005) in PwMS compared with HCs. VZV IgG seroprevalence was 97.5% in PwMS and 98.5% in HCs. In the population studied, several herpesvirus infections markers may have been influenced by the age and sex of the groups studied. The lack of a negative association of MS with CMV infection, and the observation of lower levels of HSV IgG in PwMS compared with HCs are findings worthy of further investigation.

• Journal Article Type: Article
• Acceptance Date: Jun 6, 2024
• Online Publication Date: Jun 12, 2024
• Publication Date: 2024-06
• Deposit Date: Jun 15, 2024
• Publicly Available Date: Jun 19, 2024
• Journal: Pathogens
• Electronic ISSN: 2076-0817
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 6
• Article Number: 499
• DOI: https://doi.org/10.3390/pathogens13060499
• Keywords: multiple sclerosis; Italy; human herpesviruses; Epstein–Barr virus; cytomegalovirus; herpes simplex virus; varicella zoster virus; seroprevalence; antibody levels
• Publisher URL: https://www.mdpi.com/2076-0817/13/6/499