Epstein-Barr Virus Load Correlates with Multiple Sclerosis-Associated Retrovirus Envelope Expression

Abstract

pHERV-W ENV and syncytin-1, the envelope proteins of the human endogenous retrovirus W family (HERV-W), have been proposed as etiological factors for MS development. In addition, herpesviruses, such as the Epstein-Barr virus (EBV) and the human herpesvirus 6A/B (HHV-6A/B), have been also strongly associated with the disease. This work aims to study the possible link between viral loads and antibody titers against EBV and HHV-6A/B and the pHERV-W ENV/syncytin-1 protein/gene expression. For this purpose, we conducted a 12-month longitudinal study involving 98 RRMS patients. Peripheral blood samples were obtained from each patient. Serum antibody titers against EBV and HHV-6A/B were determined by ELISA, while viral loads were analyzed using qPCR. HLA MS-related alleles were also genotyped. pHERV-W ENV/syncytin-1 protein and gene expression levels in immune cells were assessed by flow cytometry and qPCR, respectively. We found that the 12-month variation of the pHERV-W ENV gene expression levels positively correlated with the variation of the EBV viral load, especially in those patients with high baseline EBV loads. Therefore, these results could support previous studies pointing to the transactivation of pHERV-W ENV by EBV. However, further studies are needed to better understand this possible relationship.

Correlation between antibodies against the pathogenic pHERV‐W envelope protein and the inflammatory phase of multiple sclerosis

“…Furthermore, environmental viruses associated with MS can activate the promoters of the transactivation p HERV‐W, leading to epigenetic dysregulation that may influence the development of the disease [32]. Pérez‐Pérez et al [33] reported a positive correlation between the 12‐month variation of EBV load and the 12‐month variation of p HERV‐W ENV gene expression in RRMS patients, supporting the idea of potential transactivation of p HERV‐W by MS‐associated viruses [33]. Positive correlations were also observed between the levels of p HERV‐W protein expression and anti‐HHV‐6A/B IgM antibodies in T lymphocytes and NK cells [34].…”

The Molecular Link Between TDP-43, Endogenous Retroviruses and Inflammatory Neurodegeneration in Amyotrophic Lateral Sclerosis: a Potential Target for Triumeq, an Antiretroviral Therapy

“…Several studies have identified increased levels of HERV-W env protein within brain tissue and PBMCs from MS patients compared to healthy controls [ 149 – 152 ]. The reactivation of HERV-W and the association with MS have been proposed to be caused by an exogenous viral infection from Epstein-Barr virus [ 148 , 153 , 154 ].…”

Ocrelizumab B cell depletion has no effect on HERV RNA expression in PBMC in MS patients

“…EBV replication in B cells triggers HERV-W and HERV-K expression [13][14][15][16] initiating a cascade of stimulation of inflammation [17][18][19] and cross reactivity with myelin oligodendrocyte protein (MOG) 20 . HERV-W and EBV expression levels are also associated and EBV and HERV-W loads are correlated in MS patients undergoing therapy 21 . An additional line of evidence linking HERV-W proteins to MS pathogenesis has shown HERV-W expression in microglia (brain-resident myeloid cells) associates with axons inducing a degenerative phenotype resulting in damage to myelinated axons 22 .…”