Metagenomic and reverse transcriptase methodologies employed to detect herpesvirus DNA in spinal fluid of multiple sclerosis (MS) patients

Study provides little evidence for or against a possible role for HHV-6 or EBV in the pathogenesis of MS. 

Multiple sclerosis (MS) has been linked to various herpesviruses, most prominently, EBV and HHV-6 (Komaroff 2020). It has been proposed that HHV-6 may trigger demyelination by molecular mimicry of the virus-encoded U-24 protein to myelin basic protein (Tejada-Simon 2003).

Perlejewski of the Medical University of Warsaw used both RT-PCR/PCR as well as shotgun DNA/RNA-based metagenomics to examine cerebrospinal fluid (CSF) of 34 MS patients and 13 controls and found HHV-6 as the most frequently detected virus (n =3, 8.92%). This was followed by EBV (n=2, 5.88%), VZV (n=1, 2.94%), Enterovirus (n=1, 2.94%). Only EBV was identified among controls (7.69%). There was no statistically significant difference in viral prevalence when cases were compared to controls, but the study was small and poorly powered.

RT-PCR/PCR seemed to be more sensitive than metagenomic analysis as the metagenomic analysis was unable to detect eukaryotic viruses. 

The literature that most persuasively suggests that HHV-6 may play a role in the pathogenesis of some cases of MS is based largely on a study of brain tissue rather than CSF. It is not clear that studies of CSF can provide useful information as to the possible role of HHV-6 in MS.

In contrast, the strongest evidence linking EBV to MS comes not from either brain tissue or CSF but rather from serologic studies (Bjornevik 2022). Therefore, the results of this study do not provide much evidence in favor of or against the role that HHV-6 and EBV might play in the pathogenesis of MS. 

Read the full article: Perlejowski 2020