Multiple sclerosis (MS)-associated retrovirus (MSRV)/HERV-W (human endogenous retrovirus W)and Human herpesvirus 6 (HHV-6) are the two most studied (and discussed) viruses as environmental co-factors that trigger MS immunopathological phenomena. Autopsied brain tissues from MS patients and controls and peripheral blood mononuclear cells (PBMCs) were analysed. Quantitative RT-PCR and PCR with primers specific for MSRV/HERV-W env and pol and HHV-6 U94/rep and DNA-pol were used to determine virus copy numbers. Brain sections were immunostained with HERV-W env-specific monoclonal antibody to detect the viral protein. All brains expressed MSRV/HERV-W env and pol genes. Phylogenetic analysis indicated that cerebral MSRV/HERV-W-related env sequences, plasmatic MSRV, HERV-W and ERVWE1 (syncytin) are related closely. Accumulation of MSRV/HERV-W-specific RNAs was significantly greater in MS brains than in controls (P=0.014 vs healthy controls; P=0.006 vs pathological controls). By immunohistochemistry, no HERV-W env protein was detected in control brains, whereas it was upregulated within MS plaques and correlated with the extent of active demyelination and inflammation. No HHV-6-specific RNAs were detected in brains of MS patients; one healthy control had latent HHV-6 and one pathological control had replicating HHV-6. At the PBMC level, all MS patients expressed MSRV/HERV-W env at higher copy numbers than did controls (P=0.00003). Similar HHV-6 presence was found in MS patients and healthy individuals; only one MS patient had replicating HHV-6. This report, the first to study both MSRV/HERV-W and HHV-6, indicates that MSRV/HERV-W is expressed actively in human brain and activated strongly in MS patients, whilst there are no significant differences between these MS patients and controls for HHV-6 presence/replication at the brain or PBMC level. INTRODUCTIONThe aetiopathogenesis of multiple sclerosis (MS) disease is complex and debated. Immunopathogenic phenomena are thought to be triggered by environmental (viral?) factors operating on a predisposing genetic background (Noseworthy et al., 2000). Among the viruses suggested as MS co-factors are ubiquitous members of the family Herpesviridae, Human herpesvirus 6 (HHV-6) (AlvarezLafuente et al., 2004;Moore & Wolfson, 2002) and Epstein-Barr virus (EBV) (Christensen, 2006), and a human endogenous retrovirus (HERV), the MS-associated retrovirus (MSRV) (Dolei, 2005;Perron et al., 1989), a member of the HERV-W multicopy family; links between HERVs and some human diseases have been observed increasingly (Dolei, 2006). HHV-6 can be neurotropic, can become latent and be reactivated, and has potential immunopathogenic properties. Meta-analyses indicate that the available reports provide some support for a link between HHV-6 and MS, but none shows causative relationships (Clark, 2004;Moore & Wolfson, 2002 Firouzi et al., 2003). Activities strikingly concordant with findings on MSRV and MS (Dolei et al., 2002;Firouzi et al., 2003;Lafon et al., 2002;Perron et al., 2005; Sotgiu et al., ...

No abstract

The authors performed a longitudinal evaluation of multiple sclerosis (MS) patients, during 1 year of therapy with interferon-beta (IFN-beta), by clinical examination and detection of presence in the blood and viral load of MS-associated retrovirus (MSRV), by MSRVenv-specific, fully quantitative, real time reverse transcriptase-polymerase chain reaction (RT-PCR). MSRV load in the blood was directly related to MS duration and fell below detection limits within 3 months of IFN therapy; one patient had strong progression, accompanied by total MSRV rescue. These findings suggest that evaluation of plasmatic MSRV could be considered the first prognostic marker for the individual patient, to monitor disease progression and therapy outcome.

Syncytin-1 has a physiological role during early pregnancy, as mediator of trophoblast fusion into the syncytiotrophoblast layer, hence allowing embryo implantation. In addition, its expression in nerve tissue has been proposed to contribute to the pathogenesis of multiple sclerosis (MS). Syncytin-1 is the env glycoprotein of the ERVWE1 component of the W family of human endogenous retroviruses (HERV), located on chromosome 7q21-22, in a candidate region for genetic susceptibility to MS. The mechanisms of ERVWE1 regulation in nerve tissue remain to be identified. Since there are correlations between some cytokines and MS outcome, we examined the regulation of the syncytin-1 promoter by MS-related cytokines in human U-87MG astrocytic cells. Using transient transfection assays, we observed that the MS-detrimental cytokines TNFalpha, interferon-gamma, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-beta is inhibitory. The effects of cytokines are reduced by the deletion of the cellular enhancer domain of the promoter that contains binding sites for several transcription factors. In particular, we found that TNFalpha had the ability to activate the ERVWE1 promoter through an NF-kappaB-responsive element located within the enhancer domain of the promoter. Electrophoretic mobility shift and ChIP assays showed that TNFalpha enhances the binding of the p65 subunit of NF-kappaB, to its cognate site within the promoter. The effect of TNFalpha is abolished by siRNA directed against p65. Taken together, these results illustrate a role for p65 in regulating the ERVWE1 promoter and in TNFalpha-mediated induction of syncytin-1 in multiple sclerosis.

Introduction: Imported parasitosis, which do not require an invertebrate vector, are extremely dangerous and can lead to the occurrence of disease in currently parasite free areas. In the present study we report a case of multi-parasitic infection in a young immigrant from Ghana to Italy caused by filaria, Schistosoma sp. and Strongyloides sp. Case presentation: A 27-year-old Ghanaian man attended the Hospital of Nuoro (Sardinia), Italy, at the end of August 2015, claiming pain to the kidney and hypertensive crisis; the patient presented with dyspnea and epistaxis, chronic itchy skin of the back, shoulders, arms and legs, anuria and high creatinine, metabolic acidosis and hypereosinophilic syndrome. Serological test for parasitic infections were done, and showed a marked positivity for filaria, Schistosoma sp. and Strongyloides sp. The patient started the treatment immediately with two doses per day of Bassado Antibiotic (tetracycline) for twenty days and then with a single dose of 3 mg of ivermectin that was repeated after 3 months. Conclusions: Immigrant patients from endemic areas who show clinical signs, such as a general itching on the back, shoulders and arms and legs, should have a thorough history in order to make early diagnosis and prevent further complications. Therefore, general practitioners and doctors in Europe and in other parasitosis non-endemic countries, should consider to test for parasites in any immigrant from endemic countries to aid in establishing the final diagnosis and prevent further complications.