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

Author:

Maple Peter A.12ORCID,Tanasescu Radu12ORCID,Constantinescu Cris S.13ORCID,Valentino Paola4ORCID,Capobianco Marco4,D’Orso Silvia5,Borsellino Giovanna5ORCID,Battistini Luca5ORCID,Ristori Giovanni56,Mechelli Rosella78ORCID,Salvetti Marco69ORCID,Gran Bruno12ORCID

Affiliation:

1. Mental Health and Clinical Neuroscience Academic Unit, University of Nottingham School of Medicine, Nottingham NG7 2UH, UK

2. Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham NG5 1PB, UK

3. Cooper Neurological Institute, Cooper Medical School of Rowan University, Camden, NJ 08103, USA

4. Neuroscience Institute, Cavalieri Ottolenghi, 10043 Orbassano, Italy

5. Department of Experimental Neuroscience, IRCSS Foundation Santa Lucia, 00179 Rome, Italy

6. Department of Neurosciences, Mental Health and Sensory Organs, Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome, 00185 Rome, Italy

7. Department of Human Science and Promotion of Quality of Life, San Raffaele Open University, 00166 Rome, Italy

8. IRCCS, San Raffaele Roma, 00166 Rome, Italy

9. Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy

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.

Funder

Italian Multiple Sclerosis Foundation

Publisher

MDPI AG

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