“As you know I think EBV causes MS, i.e. I think it is the pivotal factor in the causal pathway that leads to the onset of the disease. Studies have consistently shown that the immune response to EBNA-1 (EBV associated nuclear antigen-1) is increased in people at risk of MS and/or who have MS. Please note the use of ‘and/or’, because most people develop biological disease, i.e. MS, before their first symptoms. EBNA-1 is a so called latency programme antigen and keeps the EBV genome in hibernation. Some feel EBNA-1 is a molecular mimic and triggers cross-reactive immune responses to self-proteins. This is one of the main EBV hypotheses. Another hypothesis is that EBV infects cells within the brain and spinal cord and hence stimulates immune responses, by up-regulating innate immune mechanisms, or danger signals. If EBV does infect the central nervous system you would expect the nervous system to be enriched for T-cells reactive against EBNA-1. The small study below suggests that is the case. However, it does not show a difference between MS and other inflammatory conditions. Maybe this study is just detecting CD8+ T-cells that are prostitutes?”
Erdura et al. EBNA1 antigen-specific CD8 + T cells in cerebrospinal fluid of patients with multiple sclerosis. Journal of Neuroimmunology. Available online 19 March 2016 – In Press.
Epidemiological data suggests that Epstein–Barr virus may be involved in the pathogenesis of Multiple Sclerosis (MS). We aimed to determine the frequency of CD8 +T cells specific for one EBNA1-derived epitope (HPVGEADYFEY) in cerebrospinal fluid (CSF) and blood of patients with MS and other inflammatory neurological diseases (OIND). The frequency of specific CD8 + T cells was assessed by HLA-class-I-binding pentamers restricted to HLA-B35. The frequency of HPVGEADYFEY-specific CD8 + T cells did neither differ significantly in blood nor CSF in MS compared to OIND, but was consistently higher in CSF compared to blood regardless of diagnosis.
7 thoughts on “ResearchSpeak: EBV specific T-cells enriched in the spinal fluid”
This kind of sounds to me as though antivirals for EBV don't have much chance of improving MS outcomes in patients who have already developed MS – if EBNA-1 is the issue – in terms of generating autoimmunity. These molecules will persist in the body even if the EBV virus were to be eliminated, would they not? So the horse bolts at this time? The hope of Charcot would therefore be soley the development of a preventative measure? Not a cure?
Taking antivirals could be beneficial though, even long after infection.If you take chronic shingles as an example, the antiviral drugs help decrease the severity and the frequency of the attacks.
If EBV is indeed the main player, gene editing (CRISPR!) is getting close to removing the viruses or decreasing the viral loads, see this HIV publication: http://www.nature.com/articles/srep22555
http://www.pnas.org/content/111/36/13157.full.pdfAnon 2:23. Yes this strategy of gene editing via CRISPR/cas9 may be the way to eliminate latent EBV in B-cells. Whole genome editing of EBV in Burkitt's Lymphoma and Nasopharyngeal carcinoma may be possible treatments.
If latent EBV is driving MS pathology snip out the EBV DNA in our B-cells and see what happens. Simple, no?
Another option is to retrain the immune system against EBV. See Michael Pender's work http://www.msra.org.au/immune-control-epstein-barr-virus-ms
EBV lives in B cells and epithilial cells. The brain contains epithilial cells. When the brain inflames, damaged epithilial cells may leak EBV particles in CSF and later in blood, leading to increased immune response. That is why:1. EBV-seropositive PwMS are more positive than EBV-seropositive controls2. "The frequency of HPVGEADYFEY-specific CD8 + T cells did neither differ significantly in blood nor CSF in MS compared to OIND, but was consistently higher in CSF compared to blood regardless of diagnosis."