Tag: viral reactivation

Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients

Abstract:

BACKGROUND: HHV-6 is a ubiquitous virus and its infection usually occurs in childhood and then becomes a latent infection. HHV-6 reactivation has been shown to play a role in the pathogenesis of AIDS and several other diseases.

OBJECTIVES: To determine what role HHV-6 infection or reactivation plays in the pathogenesis of multiple sclerosis (MS) and chronic fatigue syndrome (CFS).

RESULTS: Twenty-one MS and 35 CFS patients were studied and followed clinically. In these patients, we measured HHV-6 IgG and IgM antibody levels and also analyzed their peripheral blood mononuclear cells (PBMCs) for the presence of HHV-6, using a short term culture assay. In both MS and CFS patients, we found higher levels of HHV-6 IgM antibody and elevated levels of IgG antibody when compared to healthy controls. Seventy percent of the MS patients studied contained IgM antibodies for HHV-6 late antigens (capsid), while only 15% of the healthy donors (HD) and 20% of the patients with other neurological disorders (OND) had HHV-6 IgM antibodies. Higher frequency of IgM antibody was also detected in CFS patients (57.1%) compared to HD (16%). Moreover, 54% of CFS patients exhibited antibody to HHV-6 early protein (p41/38) compared to only 8.0% of the HD. Elevated IgG antibody titers were detected in both the MS and the CFS patients. PBMCs from MS, CFS and HD were analyzed in a short term culture assay in order to detect HHV-6 antigen expressing cells and to characterize the viral isolates obtained as either Variant A or B. Fifty-four percent of MS patients contained HHV-6 early and late antigen producing cells and 87% of HHV-6 isolates were Variant B. Isolates from CFS, patients were predominately Variant A (70%) and isolates from HD were predominately Variant B (67%). Moreover, one isolate from OND was also Variant B. Persistent HHV-6 infection was found in two CFS patients over a period of 2.5 years and HHV-6 specific cellular immune responses were detected in PBMCs from ten CFS patients.

CONCLUSION: In both MS and CFS patients, we found increased levels of HHV-6 antibody and HHV-6 DNA. A decrease in cellular immune responses was also detected in CFS patients. These data suggest that HHV-6 reactivation plays a role in the pathogenesis of these disorders.

 

Source: Ablashi DV, Eastman HB, Owen CB, Roman MM, Friedman J, Zabriskie JB, Peterson DL, Pearson GR, Whitman JE. Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. J Clin Virol. 2000 May;16(3):179-91. http://www.ncbi.nlm.nih.gov/pubmed/10738137

 

Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports

Abstract:

Specific Human Herpes virus-6 (HHV-6) transfer factor (TF) preparation, administered to two chronic fatigue syndrome patients, inhibited the HHV-6 infection. Prior to treatment, both patients exhibited an activated HHV-6 infection. TF treatment significantly improved the clinical manifestations of CFS in one patient who resumed normal duties within weeks, whereas no clinical improvement was observed in the second patient. It is concluded that HHV-6 specific TF may be of significant value in controlling HHV-6 infection and related illnesses.

 

Source: Ablashi DV, Levine PH, De Vinci C, Whitman JE Jr, Pizza G, Viza D. Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports. Biotherapy. 1996;9(1-3):81-6. http://www.ncbi.nlm.nih.gov/pubmed/8993763

 

Chronic intestinal candidiasis as a possible etiological factor in the chronic fatigue syndrome

Abstract:

The chronic candidiasis syndrome, also known as the Candida-related complex, putatively caused by the overgrowth of Candida albicans in the gastrointestinal tract and secondarily in the genital organs, is briefly described.

Patients with this disorder have many of the same symptoms as those with the chronic fatigue syndrome, except for the recurrent flu-like symptoms of the latter disorder. The positive response of a large number of patients with the chronic fatigue syndrome (CFS) to an oral antifungal agent and a diet for intestinal candidiasis has been described by another clinician.

There is evidence that Candida albicans infection of the mucous membranes depresses T cell and natural killer (NK) cell function. Similar abnormalities of immune function are found in the CFS. The function of cytotoxic T cells, T helper cells, and NK cells is important in preventing reactivation of infections from Epstein-Barr virus, cytomegalovirus, and other herpesviruses.

Reactivation of one or more of these viruses could lead to the expression of the flu-like symptoms in the CFS. Yet the immune dysfunction found in this disorder has been considered the primary underlying causal factor.

It is proposed that chronic intestinal candidiasis may be an agent which leads to immune depression in many CFS patients and therefore that it could be a causal factor in CFS.

 

Source: Cater RE 2nd. Chronic intestinal candidiasis as a possible etiological factor in the chronic fatigue syndrome. Med Hypotheses. 1995 Jun;44(6):507-15. http://www.ncbi.nlm.nih.gov/pubmed/7476598

 

Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome

Abstract:

To test for an association between chronic fatigue syndrome (CFS) and infections with Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), antibodies to these viruses were tested in the serum from three groups of individuals: (1) 10 CFS patients with chronic fatigue beginning with a clinical pattern of acute infectious mononucleosis [IM; true chronic IM (CIM)]; (2) 10 CFS patients whose illness did not start with acute IM (non-CIM), and (3) healthy controls.

High EBV antibody titers were demonstrated in most patients. Antibodies to ZEBRA, a product of the immediate early EBV gene BZLF1, were detected in the serum of CFS patients at a higher frequency than in healthy controls. Antibody titers to HHV-6 and HHV-7 were also higher in the patients with CFS than in the controls. These results are consistent with the view that CFS patients may have reactivations of EBV, HHV-6 and HHV-7.

 

Source: Sairenji T, Yamanishi K, Tachibana Y, Bertoni G, Kurata T. Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome. Intervirology. 1995;38(5):269-73. http://www.ncbi.nlm.nih.gov/pubmed/8724857

 

Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome

Abstract:

 

Peripheral blood mononuclear cells collected from 13 patients with chronic fatigue syndrome and 13 healthy controls were analyzed for the presence of human herpesvirus 6 (HHV-6) DNA by variant-specific polymerase chain reaction and dot blot hybridization. HHV-6 DNA was detected in 7 of 13 (53%) patients, and of those 7 patients, 4 were positive for HHV-6 variant A DNA and 3 were for variant B. No HHV-6 DNA was detected in the controls. Serum antibody titers to the late antigen and antibody prevalence to the early antigen of HHV-6 were significantly higher in the patient group. These results suggest active replication of HHV-6 in patients with chronic fatigue syndrome.

 

Source: Yalcin S1, Kuratsune H, Yamaguchi K, Kitani T, Yamanishi K. Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome. Microbiol Immunol. 1994;38(7):587-90. http://onlinelibrary.wiley.com/doi/10.1111/j.1348-0421.1994.tb01827.x/pdf (Full article)

 

Pathogenic tracks in fatigue syndromes

Abstract:

This review analyses the recent literature devoted to two related fatigue syndromes: chronic fatigue syndrome (CFS) and acute onset postviral fatigue syndrome (PVFS). The articles are grouped into five pathogenic tracks: infectious agents, immune system, skeletic muscle, hypothalamo-pituitary-adrenal (HPA) axis and psychiatric factors.

Although a particular infectious agent is unlikely to be responsible for all CFS cases, evidence is shown that host-parasite relationships are modified in a large proportion of patients with chronic fatigue. Antibody titres against infectious agents are often elevated and replication of several viruses could be increased.

Chronic activation of the immune system is also observed and could be due to the reactivation of persistent or latent infectious agents such as herpes viruses (i.e. HHV-6) or enteroviruses. It could also be favorised by an impaired negative feedback of the HPA axis on the immune system.

A model is proposed where the abnormalities of the HPA axis are primary events and are mainly responsible for a chronic activation of the immune system which in turn induces an increased replication of several viruses under the control of cellular transcription factors. These replicating viruses together with cytokines such as TNF-alpha would secondarily induce functional disorders of muscle and several aspects of asthenia itself.

 

Source: Moutschen M, Triffaux JM, Demonty J, Legros JJ, Lefèbvre PJ. Pathogenic tracks in fatigue syndromes. Acta Clin Belg. 1994;49(6):274-89. http://www.ncbi.nlm.nih.gov/pubmed/7871934

 

Chronic fatigue syndrome, a case of high anti-HHV-6 antibody titer and one associated with primary hyperaldosteronism

Abstract:

Two cases of chronic fatigue syndrome (CFS) were reported which were suggestive for the study of the etiology and a cure for CFS.

Case 1: A 31-year-old woman was admitted for chronic fatigue syndrome. Examination revealed a high titer of anti HHV-6 antigen of x2560 and an increased percentage of suppressor T lymphocytes in the peripheral blood. HHV-6 was speculated to be reactivated and stimulating the immune system in CFS.

Case 2: A 46-year-old woman suffering from CFS had been in remission for 6 years. She was admitted for hypertension associated with right adrenal adenoma and hyperaldosteronism. After right adrenalectomy, there was a recurrence of high fever and other CFS symptoms. It was suggested that CFS symptoms may be ameliorated by aldosterone.

 

Source: Kato Y, Kamijima S, Kashiwagi A, Oguri T. Chronic fatigue syndrome, a case of high anti-HHV-6 antibody titer and one associated with primary hyperaldosteronism. Nihon Rinsho. 1992 Nov;50(11):2673-8. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337563

 

Symptoms, signs and laboratory findings in patients with chronic fatigue syndrome

Abstract:

This review summarizes the symptoms, signs and laboratory abnormalities seen in 59 patients with chronic fatigue syndrome (CFS), 2 patients with post-infectious CFS and in 26 patients with possible CFS whose illnesses fulfill the criteria proposed by the study group of the Ministry of Welfare, Japan.

The characteristic symptoms and signs of CFS are prolonged generalized fatigue following exercise, headache, neuropsychological symptoms, sleep disturbance and mild fever. In possible CFS patients, the frequency of mild fever, muscle weakness, myalgia and headache is low.

Our standard hematologic and laboratory tests revealed a few abnormality in patients with CFS. The characteristic abnormality in CFS patients is the low values of 17-Ketosteroid-Sulfates/creatinine in morning urine and the acylcarnitine deficiency. It seems likely that this deficiency of acylcarnitine induces an energy deficit in the skeletal muscle, resulting in general fatigue, myalgia, muscle weakness and postexertional malaise in CFS patients. Virologic studies revealed no evidence of retrovirus infection with HTLV-1, HTLV-2 and HIV, but the reactivation of HHV-6 infection was apparent.

 

Source: Kuratsune H, Yamaguti K, Hattori H, Tazawa H, Takahashi M, Yamanishi K, Kitani T. Symptoms, signs and laboratory findings in patients with chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2665-72. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337562

 

Human herpesvirus-6 (HHV-6) (short review)

Abstract:

Human Herpesvirus-6 is the etiological agent of Roseola infantum and approximately 12% of heterophile antibody negative infectious mononucleosis. HHV-6 is T-lymphotropic, and readily infects and lyses CD4+ cells. The prevalence rate of HHV-6 in the general population is about 80% (as measured by IFA) with an IgG antibody titer of 1:80. A lower prevalence, however, is observed in some countries.

HHV-6 is reactivated in various malignant and non-malignant diseases as well as in Chronic Fatigue Syndrome and transplant patients. Furthermore, elevated antibody titers were also observed in lymphoproliferative disorders, auto-immune diseases and HIV-1 positive AIDS patients. There appears to be some strain variability in HHV-6 isolates.

The GS isolates of HHV-6 (prototype) was resistant to Acyclovir, Gancyclovir, but its replication was inhibited by Phosphonoacetic acid and Phosphoformic acid. HHV-7 isolated from healthy individuals showed, by restriction analysis, that 6 out of 11 probes derived from two strains of HHV-6, cross-hybridized with DNA fragments, derived from HHV-7.

 

Source: Ablashi DV, Salahuddin SZ, Josephs SF, Balachandran N, Krueger GR, Gallo RC. Human herpesvirus-6 (HHV-6) (short review). In Vivo. 1991 May-Jun;5(3):193-9. http://www.ncbi.nlm.nih.gov/pubmed/1654146

 

Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome

Abstract:

Forty-one patients with recurrent fatigue were studied for evidence of symptom clustering, abnormal laboratory findings and infection with novel viruses. Symptom enquiry and investigations were repeated 4 months later.

Four patients were found to have diseases compatible with their symptoms. In those remaining, an initial acute onset of symptoms was associated with an intermittent course, tender glands and a raised number of T suppressor lymphocytes. Raised numbers of T suppressor lymphocytes at follow-up correlated with resolution of symptoms. Antibodies to human herpesvirus 6 (HHV-6) were found in 75% of the patients as compared to 53% of a control group and more patients than controls were strongly seropositive.

Some patients with chronic fatigue have a pattern of illness which suggests glandular fever, although acute infection with Epstein-Barr virus (EBV) is not demonstrated. Primary or reactivation infection with HHV-6 may have a role in this syndrome.

 

Source:  Read R, Larson E, Harvey J, Edwards A, Thomson B, Briggs M, Fox J. Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome. J Infect. 1990 Sep;21(2):157-65. http://www.ncbi.nlm.nih.gov/pubmed/2172387