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Human endogenous retrovirus W family envelope proteins (pHERV-W ENV/syncytin-1) have been repeatedly associated with multiple sclerosis (MS). Here, we have focused on the study of pHERV-W ENV/syncytin-1 expression levels in MS patients (relapsing and progressive forms) and in healthy donors (HD) and on exploring their possible relationship with Epstein-Barr virus (EBV) and human herpesvirus-6A/B (HHV-6A/B). We included blood samples from 101 MS patients and 37 HD to analyze antiviral antibody titers by ELISA and pHERV-W ENV/syncytin-1 expression levels by flow cytometry as well as by qPCR. Patients with relapsing MS forms showed significantly higher pHERV-W ENV/syncytin-1 protein and gene expression levels than HD. Progressive MS patients also showed significantly higher protein and gene expression levels than both HD and relapsing MS patients. Regarding antiviral antibodies titers, anti-HHV-6A/B IgM levels were positively correlated with pHERV-W ENV/syncytin-1 protein expression levels in patients with relapsing MS, while in the progressive forms patients this correlation was found with anti-HHVA/B IgG levels. Therefore, pHERV-W ENV could be involved in MS pathogenesis, playing a role in relapsing and progressive forms. Besides, anti-HHV-6A/B antibodies positively correlated with pHERV-W ENV expression. Further studies are needed to better understand this possible relationship.

Background One of the risk factor to develop progressive multifocal leukoencephalopathy (PML) among natalizumab-treated patients is the presence and high levels of anti-JCV antibodies. Our purpose was to test the association of different clinical and demographic variables with the presence and levels of anti-JCV antibodies in a Spanish cohort of multiple sclerosis (MS) patients during natalizumab treatment Materials and methods All MS patients from two hospitals with at least one measure of the anti-JCV antibodies levels (2011-2014) were recruited, among them two PML cases. Anti-JCV antibody levels were assessed using two-step ELISA Results 1061 patients (16.3% natalizumab-treated) participated in this study. The seropositivity rate of anti-JCV antibodies was 58.2%. It increased with age (pcorrected=0.00005) and was lower among HLA-DRB1*15:01 carriers (pcorrected=0.049). The two PML patients were HLA-DRB1*15:01carriers. We had at least 3 quarterly anti-JCV antibody measurements (index value) from 137 patients, whose levels did not increase during natalizumab treatment. However, 5.8% of these patients had an increase of the index value higher of one point in a maximum of 6 months, something that was more frequently observed (p=0.054) among patients treated with immunosuppressant prior to natalizumab onset Conclusions Old age and HLA-DRB1*15:01 were the factors that influence positively and negatively respectively our anti-JCV antibody prevalence, although our both PML cases were HLA-DRB1*15:01carriers. Most of our patients showed a stable anti-JCV antibody index values during natalizumab treatment. This article is protected by copyright. All rights reserved.