HHV6 in CFS, MS, Induced CNS Dysfunction

Discussion in 'Fibromyalgia Main Forum' started by karinaxx, Jan 7, 2007.

  1. karinaxx

    karinaxx New Member

    HHV-6 in CFS

    Human Herpesvirus 6 (HHV-6) is a virus that persists in the brain tissue, and is not easily detectable by standard laboratory tests, but has long been suspected as playing a role in chronic fatigue syndrome (CFS), in conjunction with Epstein Barr Virus (EBV) the virus that causes mononucleosis. (See Reasons to suspect virus in CFS)

    The biggest problem in studying the association of this virus with CFS is that since these viruses are ubiquitous (most of us have been exposed and have antibodies) it is difficult to know which patients have active infection and which patients have a latent infection. Often, the HHV-6 virus only replicates in the brain tissue, so it is impossible to find it circulating in the serum. For these reasons, it has been difficult to prove a definitive association.

    Efforts to establish an association between HHV-6 and CFS have been complicated by a number of flawed studies that did not use assays that could not differentiate between active and latent infection. (See Past Studies of HHV-6 in CFS)

    Ironically, one of the best tests for active infection may turn out to be the old “low-tech” standard antibody test, using a high cutoff. While an HHV-6 IgG titer of say 1:640 might be perfectly normal for a 4 year old, or a teenager just over a bout of mono, it is not common in a 45 year old, and could be a sign of active infection. (IgM titers are rarely positive except after the primary infection; see Testing for HHV-6)

    Ultimately, it may be impossible to find direct evidence of the virus, and the only way to prove if an association exists is to treat for virus to see if the patients get better. This is exactly what infectious disease specialist Jose Montoya, MD from Stanford University has now treated 25 patients with long-standing fatigue and elevated antibody titers to HHV-6 and EBV. He concluded that these patients were suffering from CNS viral infections treated these patients with a strong antiviral; an astounding 88% improved dramatically. Some of these patients had been sick for over 10 years. He call this condition Virus Induced CNS Dysfunction ( http://www.vicd.info/ ) and is now planning a placebo controlled trial. (See Stanford Trial Info)

    Most physicians are reluctant to use a strong antiviral without certainty that the virus is active. Antibody levels can remain elevated for years after the primary infection and in some cases, merely indicate a healthy response to a past infection. Montoya reasoned, however that since 97% of us have had our primary infection with HHV-6 by the age of two, and highly elevated antibody levels in an adult could mean active disease. His results so far suggest that his theory is correct. Antibody levels to both HHV-6 and EBV dropped with treatment. (Montoya 2006). His strategy is bold and his initiative invaluable because he will provide clarity where diagnostic testing has failed.

    [This Message was Edited on 01/07/2007]
  2. karinaxx

    karinaxx New Member

    HHV-6 in MS

    There is growing evidence that HHV-6A plays a role in MS, either directly or indirectly as an activator of viruses such as EBV or an endogenous retrovirus such as HERV-W.

    HHV-6A DNA has been found in cell-free specimens from MS patients but not from healthy controls. (Alvarez-Lafuente 2004, Chapenko 2004, Berti 2002, Soldan 1997)
    More HHV-6 DNA is found in MS patient serum during exacerbations than during relapses. (Alvarez-Lafuente 2004)
    More HHV-6 DNA is found in MS plaques than in non-affected white matter by immunohistochemistry and in-situ PCR. (Challoner 1995, Goodman 2003)
    Lymphoproliferative response to HHV-6A is greater in MS patients than in controls; 67% of MS patients have significant lmphocyte response to HHV-6 vs 32% of controls. (Soldan 2000)
    HHV-6 intrathecal antibodies (antibodies generated in the spinal fluid) have been 22% of MS patients but 0% of controls. (Derfuss 2005)
    IgM and IgG antibodies to HHV-6 early antigen (antibodies that are only found during active infection) are significantly greater in MS patients than in controls. (Patnaik 1995, Soldan 1997, Ablashi 2000)
    Claude Genain and investigators at UCSF induced MS-like lesions in marmoset monkeys by injecting them with HHV-6A. (International Conference on HHV-6 & 7, 2006)
    The idea that infectious agents may play a significant role in MS dates back at least 200 years. Many characteristics of the disease suggest the possible involvement of pathogens, including its relapsing/remitting nature, geographic variations in distribution, and epidemics such as the reported outbreak in the Faroe Islands beginning in the 1940's.

    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
    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 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 as Borrelia 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) The HHV-6 Foundation is working with scientists and commercial diagnostic companies to produce an assay based on the early antigen protein of HHV-6. In four studies in the late nineties (when this assay was briefly available) this assay 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. 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. 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 mechanisms.

    The leading theory of CMV- induced autoimmunity in transplant patients is that cell surface protein from CMV infected tissues is incorporated into the viral envelope of CMV inducing graft-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. This is an area of current interest at the Viral Immunology Division at the NINDS at the NIH.

    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. Click here to download a summary of the studies on HHV-6 & MS.

    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 have reported an 11% reduction in prefrontal grey 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 determined 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.

  3. karinaxx

    karinaxx New Member

    HHV-6 Induced Immune Suppression

    Recent evidence demonstrates that HHV-6 (especially HHV-6A) can cause selective immunosuppression in otherwise in immunocompetent adults. HHV-6 infection can:

    Deplete CD4 T lymphocytes via direct infection and induction of apoptosis. (Grivel 2003)
    Cause a delay maturation of dendrocytes. (Lusso 2005)

    Disturb key immune activation pathways and cytokine networks including an upregulation of TNF alpha, TNF- gamma, IL-1beta and IL-10. (Flamand, Dockerell, Li) (Smith 2005 2004)

    Downregulate complement activity through the CD46 receptor and downregulation of Il-2. (Russell 2004) (Grivel 2003)

    Suppress the ability of macrophages to produce IL-12p70 upon stimulation with interferon gamma. (Smith 2005)
    HHV-6 invades the CD4 cells, adversely affecting function. HHV-6A, but not HHV-6B also invades CD8 cells.

  4. karinaxx

    karinaxx New Member

    HHV-6 Virus Induced CNS Dysfunction

    Virus Induced CNS Dysfunction describes the subset of Chronic Fatigue syndrome (CFS) patients who have elevated HHV-6 and EBV titers and clinical symptoms of a viral syndrome with neurocognitive complaints and sustained fatigue. Other viruses may also play a role in defining CFS patient subsets.

    CFS is a debilitating chronic illness of uncertain etiology. It is a clinically defined condition characterized by severe disabling fatigue and a combination of symptoms that prominently features self-reported impairment of concentration and short-term memory, sleep disturbances, and musculoskeletal pain. CFS occurs in men and women, in all age groups and in all ethnic, racial and socioeconomic groups (Buchwald et al., 1995; Jason et al., 1995, 1999; Dobbins et al., 1997; Steele et al., 1998; Reyes et al., 2003; Bierl et al., 2004; Jones et al., 2004).

    CFS often begins with a “flu-like” illness although some surveys indicate many cases have a more gradual onset. Patients with CFS have profound impaired functional status; similar to or worse than patients with several chronic illnesses including congestive heart failure, diabetes mellitus, and major depression (Komaroff et al., 1996; Buchwald et al., 1996; Hardt et al., 2001; Solomon et al., 2003). It is estimated that, independent of whether patients have sought medical attention for the illness, between 1 and 8 in 1000 US adults meet the CDC criteria for the syndrome (Reyes et al., 2003). The CDC estimates that the cost to the US economy from lost productivity alone (not including medical care costs) is $9 billion annually (Reynolds et al., 2004).

    While the pathogenesis of CFS is unknown, there is substantial evidence of an underlying biological process involved. Published evidence illustrates that patients with CFS have abnormalities in the central and autonomic nervous systems, and evidence of chronic activation of antiviral pathways and T-cells.

  5. u34rb

    u34rb New Member


    Please could you give references when you post, and if possible a link to where you have found your data?
  6. karinaxx

    karinaxx New Member


  7. DorothyVivian

    DorothyVivian New Member

    I appreciate deeply the time and efforts you, and others here, give to sharing information you've found with the rest of us! These articles are extremely helpful!
    With love, Dorothy
  8. karinaxx

    karinaxx New Member

    you are very welcome and it feels good when from time to time somebody appriciates the efforts made here by many, to share the information we are searching and sharing.

    i see that you are a painter?
    i used to paint and did the artschool in switzerland for a short period, but dont have the energy anymore to start again.
    maybe you could put one of your paintings on your profile?

    take care

  9. sturg1

    sturg1 New Member

    Hi Karina,
    Thank you for posting this information. I am considering applying for the trial at Stanford. right now I am taking Lauricidin (sp?) as an anti-viral treatment and have herxed a little. I meet with my dr to discuss this next week, which may be too late to apply.

    Thanks again!
  10. karinaxx

    karinaxx New Member

    your welcome.
    jsut make sure that you inform yourself very good. the trial is with a havy hitter AV, which has a lot of side effects and is potentially dangerous.
    i would only go for it if you have no kids and nothing to loose.
    good luck and take care
  11. LonelyHearts

    LonelyHearts New Member

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