There is growing evidence that HHV-6A plays a direct role in MS, and/or an indirect role as an activator of herpesviruses such as EBV or endogenous retroviruses such as HERV-W. Here are just a few highlighted findings from the literature on the relationship between HHV-6 infection and MS:
Reasons to suspect viruses as a cause of MS:
- All demyelinating disorders with known etiology have been caused by viruses;
- Antiviral treatments such as beta interferon have been effective in MS;
- MS symptoms wax and wane as do viral infections, particularly Herpesvirus family members;
- MS symptoms worsen with viral infections such as colds;
- Herpes infections, like MS, flare in response to stress, heat, and other infections;
- Environmental factors are more important than inherited susceptibility;
- Geographic outbreaks have been reported.
Over the years, a number of individual agents have been investigated for playing a role in MS. Candidates for triggers of MS have included mycobacterium tuberculosis, measles, mumps, rubella, retroviruses herpes simplex and varicella zoster, adenovirus, coronavirus, and vaccinia virus as well as bacteria such asBorrelia burgdorferi.
Today, attention focuses primarily on HHV-6, Epstein Barr virus (EBV), Chlamydia pneumonia (Cpn) and human endogenous retroviruses (HERVs). Since these viruses and pathogens potentiate each other, it is possible that there are many infections involved in a chain reaction, with the end result being an autoimmune process that continues long after the initial infections have passed.
One of the obstacles preventing further study of HHV-6A in serum of MS patients is that current commercial assays are not sensitive enough to detect the virus in cases of low-grade chronic infection (See Testing). However, four studies in the late 1990s (when such an assay was briefly available), showed dramatic differences between patients with MS and controls without MS.
“Molecular mimicry” involving HHV-6 has been proposed as one mechanism by which the autoimmune process could be triggered and eventually progress toward the development of MS. One study showed that certain residues on the HHV-6 genome are identical to residues of myelin basic protein. Importantly, both T-cells and antibody responses to this peptide sequences were found elevated in MS patients (Tejada-Simon 2003). Moreover, in vitro infection of glial precursor cells was found to impair cell replication and increase the expression of oligodendrocyte markers, suggesting that HHV-6 infection of the CNS may influence the neural repair mechanism (Dietrich 2004).
The leading theory of CMV-induced autoimmunity in transplant patients is that cell surface proteins from CMV-infected tissues are incorporated into the viral envelope of CMV, inducing graft-versus-host disease post transplant. Similarly, an argument could be made that myelin proteins from infected oligodendrocytes could become incorporated into the HHV-6A envelope as they enter and leave the cell, inducing CNS autoimmunity in MS and CFS patients.
Recently, many studies have suggested HHV-6A as a factor in a subset of patients with both CFS and MS. Studies using assays that differentiate between active and latent virus have shown an exceptionally strong association between HHV-6A and both MS and CFS. We now know that due to the high level of latent virus found in controls, active infection should be measured by looking for HHV-6 DNA in cell free serum or plasma. This explains why there has been confusion about the association of HHV-6A with CFS in the past. The negative studies were done primarily with testing methods that did not differentiate latent from active virus.
In MS, 88% of patients complain of moderate to severe fatigue. As in CFS, MS patients also suffer from impaired information processing speed, enlarged cerebral ventricular volumes, and altered glucose metabolism in the prefrontal cortex. Okada et al (Okada 2004) have reported an 11% reduction in prefrontal gray matter by morphometric analysis in CFS patients; a pattern also found in MS. HHV-6A DNA has been demonstrated in the cerebral spinal fluids, plaques and other neural cells in both conditions. This has led some scientists to speculate that the two disorders share a common etiology.
Antiviral therapies are already used successfully for both MS (inferferon, amantadine) and CFS (ampligen). Once active HHV-6A infections can be diagnosed in CFS and MS patients through the use of more sensitive assays in commercial laboratories, these conditions may be treatable to some degree with antiviral and immune modulators. Such treatment has the potential to relieve fatigue and improve CNS function in patients with HHV-6A viremia.
Read Kristin Loomis’ recent post calling for a clinical trial due to ample evidence that HHV-6A triggers MS in a significant subset.
Key Papers: HHV-6 & Multiple Sclerosis
