Review articleMultiple sclerosis-associated retrovirus and related human endogenous retrovirus-W in patients with multiple sclerosis: A literature review
Section snippets
Database search
A literature search was done on PubMed and Google Scholar and in total 21 publications met the criteria. The last update was on 14 June 2013. The following key words were used individually as well as in combination to do the search, multiple sclerosis, multiple sclerosis-associated retrovirus/human endogenous retrovirus-W and human endogenous retrovirus-W. The search terms (“multiple sclerosis” or “MS”) and (“multiple sclerosis associated retrovirus/human endogenous retrovirus-W” or
Criteria for the final selection of articles
The following articles were included in the review study: wherein data was derived from a sufficient sample size (15 or more patients with MS); data that included the required information for patients with MS, preferably with disease status stated (either in remission or with active disease), for healthy control subjects and/or patients with other neurological disorders (ONDs). The search was not limited by date or publication, but was limited to articles published in English.
Information extracted
Data was used to review reports on the detection rate of viral DNA, RNA, peptides/proteins and/or virions in the respective study populations. Methods used included PCR assays which were used for the molecular amplification of viral DNA or cDNA converted RNA and immuno detection was done with ELISA or immunohistochemistry to detect protein synthesis, while virions were visualized by electromicroscopy. The study populations consisted of patients with MS, both those in remission and with active
Possible bias
Bias in some of the reviewed studies has been present to some extent. The following may have affected reports to some degree: within studies different age groups as well as differences in the number of male and female participants recruited for the study and control groups may have biased findings. Between studies differences in race and ethnicity have not been well defined. Very few studies have used a large sample size and some studies have used rather small sample sizes.
Modification to protocol
Because of the relatively small number of publications on the endogenous retroviruses, a modification was needed wherein all studies that reported on MSRV/HERV-W on patients with MS were included, and with sample size numbers lower than 10 stated.
The debate around MSRV origin
The origin of MSRV as extracellular virus particles (Perron et al., 1989, Komurian-Pradel et al., 1999, Sotgiu et al., 2006) has been debated however. MSRV has been hypothesized to be an exogenous member of the HERV-W family (Perron et al., 2000, Tristem, 2000, Serra et al., 2001) and in this regard, HERVs have been reported to show resemblance to exogenous retroviruses (Ruprecht et al., 2008). Komurian-Pradel et al. (1999) and Perron et al. (2000) also suggested that MSRV may be a human
Terminology used in the current review
In their study, Ruprecht et al. (2008) use the term MSRV for nucleotide sequences and the proteins they encode obtained from extracellular particle-associated RNA and HERV-W for the endogenous retrovirus sequences present in the human genome. In the present review, however, because no consensus has been reached on the MSRV origin, the terms MSRV or MSRV/HERV-W and HERV-W will be used as reported but with respective investigated tissues noted. Results are given for MSRV and HERV-W gene sequences
MSRV in patients with MS and healthy controls
In general, RNA sequences have been reported using cDNA converted RNA as template for PCR amplification. Where techniques other than PCR have been used it has been stated.
MSRV sequences have been detected in human genomic DNA in peripheral blood leucocytes (PBLs), which suggests an endogenous retrovirus profile for MSRV, integrated into the human genome. Using fluorescence in situ hybridization (FISH), both Zawada et al. (2003) and Nowak et al. (2003) reported MSRV pol sequences not only
MSRV in patients with other neurological disorders
Nowak et al. (2003) reported MSRV pol RNA in PBL RNA from all patients with MS with active disease and in 70.6% of patients with other neurological disorders (ONDs). Mameli et al. (2007) reported MSRV/HERV-W (MSRV) env and pol RNA in RNA extracted from brain tissue from all patients with MS with active disease (N, 5) and also in all patients with OND (N, 6). These reports suggest that MSRV env and pol expressions in PBLs and brain tissue may not be specific to MS and therefore unlikely to be
HERV-W in patients with MS and healthy controls
Most studies have reported on HERV-W protein expression in brain tissue specifically but reports vary. Mameli et al. (2007), using immunohistochemistry, reported the detection of HERV-W Env protein in lesions in the brain from all patients with MS with active disease (N, 5) while none was detected in healthy control brain (N, 4). Perron et al. (2012), using immunohistology, detected HERV-W Env protein in macrophages within brain lesions in all patients with MS with active disease (N, 8) and
Conflict of interest
None declared.
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