Category: Viruses

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

 

Parvovirus B19 infection–persistence and genetic variation

Abstract:

53 patients with acute B19 infection were studied; symptoms at acute infection were rash and arthralgia (n = 26), rash (n = 7), arthralgia (n = 16), aplastic crisis (n = 3), and intrauterine fetal death (n = 1). These patients were followed for 26-85 months (mean 57 months) and re-assessed for persistent symptoms, anti-B19 antibodies, and B19 DNA. At follow-up, 7 individuals were positive for serum B19 DNA, compared with none of the controls (2-tailed p value = 0.016). All 7 of those persistently infected were women, 3 of whom had symptoms; 1 had a chronic haemolytic anaemia (initial presentation was aplastic crisis); 1 had persistent arthralgia in both knees (initial presentation was bilateral knee arthralgia); and 1 had arthralgia in one knee and chronic fatigue syndrome (initial presentation was bilateral arthralgia in knees and shoulders). For the 7 persistently infected patients, serum from the time of diagnosis of acute B19 infection was available for 4, all of which contained B19 DNA. With single-stranded conformational polymorphism (SSCP) assay of these 11 PCR products, identical SSCP types were demonstrated in 5 of 7 follow-up isolates. In 2 of the 4 cases for which both acute and follow-up PCR product was available, the SSCP type of the follow-up product was different from that of the acute product. Two B19 virus types were demonstrated in one patient (with persistent arthralgia and chronic fatigue syndrome) at follow-up assessment.

 

Source: Kerr JR, Curran MD, Moore JE, Murphy PG. Parvovirus B19 infection–persistence and genetic variation. Scand J Infect Dis. 1995;27(6):551-7. http://www.ncbi.nlm.nih.gov/pubmed/8685632

 

The Epstein-Barr virus and chronic fatigue syndrome

Abstract:

Lately discovered chronic fatigue syndrome is associated with Epstein-Barr virus infection. The objective of this paper was to detect this syndrome in our patients. 31 patients with cured acute infective mononucleosis were examined by questionnaire, physical check-up and laboratory analyses in order to detect disorders characteristic for chronic fatigue syndrome. Six months after they had been cured, out of 7 patients 5 patients complained of frequent sore throat, fatigue and exhaustion, and a year later, all 5 patients were sleepy and tired all the time. More than a year after the acute illness 19 patients were examined and in 5.6% frequent sore throat and enlarged neck lymph nodes occurred. The gathered results point to disorders characteristic for chronic fatigue syndrome in a high percentage. This pilot study should only be the beginning of examinations of this kind.

 

Source: Jovanović J, Cvjetković D, Brkić S, Madle-Samardzija N. The Epstein-Barr virus and chronic fatigue syndrome. Med Pregl. 1995;48(11-12):391-3. [Article in Croatian] http://www.ncbi.nlm.nih.gov/pubmed/8643052

 

Chronic fatigue syndrome–a controlled cross-sectional study

Abstract:

Twenty-one patients fulfilling the Center for Disease Control criteria for chronic fatigue syndrome (CFS) were examined in a controlled study. Viral antibodies and tests evaluating the immune system were investigated in the patients and in a control group of 21 sex- and age-matched individuals.

Production in vitro of the predominantly T-cell-derived cytokines interleukin-2 and interferon-gamma was significantly higher in patients with CFS compared the control group. Furthermore, the serum concentrations of IgA and IgE were significantly lower in patients with CFS; however, the values were within the normal reference range.

All other variables were similar in the two groups. This study does not suggest a clearly disordered immune system or a chronic viral infection as a major pathogenetic factor in CFS. Longitudinal studies of immunological and virological parameters in CFS are warranted as are studies on patients that are severely handicapped.

Comment in: [Chronic fatigue syndrome and angiotensin-converting enzyme]. [Ugeskr Laeger. 1995]

 

Source: Rasmussen AK, Nielsen H, Andersen V, Barington T, Bendtzen K, Hansen MB, Nielsen L, Pedersen BK, Wiik A. Chronic fatigue syndrome–a controlled cross-sectional study. Ugeskr Laeger. 1994 Nov 14;156(46):6836-40. [Article in Danish] http://www.ncbi.nlm.nih.gov/pubmed/7839498

 

Enteroviruses and the chronic fatigue syndrome

Abstract:

The possible role of enteroviral persistence in the etiology of the chronic fatigue syndrome (CFS) was investigated by serological testing, VP-1 antigen testing, and polymerase chain reaction (PCR) analysis of stool specimens as well as by viral cultures of stool–both direct and after acid treatment. No differences between 76 patients with disabling unexplained fatigue and 76 matched controls were found by serological or antigen testing.

Furthermore, no enteroviruses were isolated from any stool culture. Enterovirus was detected by PCR in one stool specimen from a patient with CFS but was not detectable in a second sample obtained from the same patient 3 months later. All stool specimens from controls were PCR-negative. These results argue against the hypothesis that enteroviruses persist in patients with CFS and that their persistence plays a role in the pathogenesis of this syndrome.

 

Source: Swanink CM, Melchers WJ, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM. Enteroviruses and the chronic fatigue syndrome. Clin Infect Dis. 1994 Nov;19(5):860-4. http://www.ncbi.nlm.nih.gov/pubmed/7893870

 

Stealth viruses as neuropathogens

Abstract:

Neuropsychiatric diseases viewed as multifaceted expression of a dysfunctional brain in which atypical responses are evoked by various sensory inputs. Disease entities have traditionally been classified according to the predominant manifestation ( ) without regard to the overlapping features of many of the diseases (+/-). Thus, mild to moderate pain, mood, cognitive, and neurosomatic symptoms are frequently present in chronic fatigue syndrome (CFS) patients. Fibromyalgia syndrome (FMS) is listed as an example of a predominantly chronic pain syndrome. Affect (mood) disorders include depression (Depress.), anxiety, panic reactions, blunted affect, mania, etc. Schizophrenia (Schizo.) is listed as an example of a major cognitive psychosis. Autism as well as various forms of dementia would be included in this category. Irritable bowel syndrome (IBS) is an example of a neurosomatic disease.

 

Source: Martin WJ. Stealth viruses as neuropathogens. CAP Today. 1994 Oct;8(10):67-70. http://www.ncbi.nlm.nih.gov/pubmed/10150189

 

Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?

Abstract:

As a test of the hypothesis that elevated titers of viral antibodies in patients with chronic fatigue syndrome (CFS) are due to a nonspecific polyclonal immune response, antibodies to Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and 14 enteroviruses in 20 patients with CFS and 20 age- and gender-matched controls were simultaneously measured.

Similarly, titers of IgG to herpes simplex virus (HSV) types 1 and 2 were measured in 18 of these cases and in the respective controls. IgG to EBV viral capsid antigen (VCA) was present at titers > or = 1:320 in 55% of cases vs. 15% of controls (P = .02).

The geometric mean titers of early antigen antibody to EBV, HHV-6 IgG, and HSV-1 and HSV-2 IgG were not significantly different among cases and controls. Of the 14 enteroviral antibodies tested for, only those to coxsackieviruses B1 and B4 were present at significant titers (> or = 1:8) in cases vs. controls (P = .02 and P = .001, respectively).

Of the cases, 19 (95%) had either an EBV VCA IgG titer > or = 1:320 or a coxsackievirus B1 or B4 antibody titer > or = 1:8, a percentage significantly higher than that of controls (40%; P = .0004). Titers of EBV VCA IgG and coxsackievirus B1 and B4 antibodies were simultaneously elevated in only 20% of cases.

There was no correlation between elevated titers of EBV VCA IgG and IgG to HHV-6, HSV-1, and HSV-2 or antibody to coxsackieviruses B1 and B4 in the cases. The prevalence of reported allergies to medications or other substances was identical in both groups (60%). These findings suggest that in the majority of cases of CFS, elevation of viral antibody titers is not due to a nonspecific polyclonal immune response.

Comment in: Viral antibodies in chronic fatigue syndrome. [Clin Infect Dis. 1995]

 

Source: Manian FA. Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response? Clin Infect Dis. 1994 Sep;19(3):448-53. http://www.ncbi.nlm.nih.gov/pubmed/7811864

 

Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome

Abstract:

An atypical virus, cytopathic for human and animal fibroblasts, was repeatedly cultured from a patient with chronic fatigue syndrome. Viral particles, suggestive of cytomegalovirus (CMV) were seen by electron microscopy. Infected cells did not, however, stain with antisera specific for CMV, herpes, simplex virus, or human herpes-virus-6. Polymerase chain reaction (PCR) assays for these viruses were also negative.

Two distinct products of approximately 1.5 kilobase pairs were amplified from virally infected cells using the human T lymphotropic virus-II tax gene reactive primer, SK44, in low stringency PCR. Sequencing of one of the amplified products showed a region of highly significant partial homology with the UL34 gene of CMV.

The sequence of the other PCR product did not correspond with CMV or any other virus. DNA was extracted from the material pelleted by ultracentrifugation of filtered culture supernatants. It migrated in agarose gels as a single band of approximately 20 kpb. The banded DNA was digested with EcoRI and cloned. A 2.2 kbp plasmid containing the CMV-related sequence identified within the PCR product was recovered.

Sequencing of this plasmid extended the region of partial sequence homology with CMV to include a portion of the UL35 gene of CMV. Initial sequencing of additional plasmids has confirmed the partial relatedness to CMV. The data indicate a novel type of CMV-related “stealth” virus that is able to establish a clinically persistent human infection.

 

Source: Martin WJ, Zeng LC, Ahmed K, Roy M. Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome. Am J Pathol. 1994 Aug;145(2):440-51. http://www.ncbi.nlm.nih.gov/pubmed/8053501

 

Biological and molecular characteristics of human herpesvirus 7: in vitro growth optimization and development of a syncytia inhibition test

Abstract:

Two isolates of human herpesvirus 7 (HHV-7) were recovered from phytohemagglutinin-activated peripheral blood mononuclear cells of a patient with chronic fatigue syndrome and of a healthy blood donor. A genetic polymorphism between the two isolates was detected by Southern blot analysis using a novel HHV-7 genomic clone (pVL8) as a probe. We developed optimized conditions for the in vitro propagation of HHV-7 by using enriched populations of activated CD4+ T lymphocytes derived from normal peripheral blood, resulting in the production of high-titered extracellular virus (> 10(6) cell culture infectious doses/ml). Bona fide syncytia formation was documented both in normal CD4+ T lymphocytes and in the Sup-T1 CD4+ T-cell line following infection with high-titered HHV-7. To identify neutralizing antibodies to HHV-7, a syncytia-inhibition test was developed. Variable titers of syncytia-neutralizing antibodies were detected in all the human sera tested, thus confirming the high prevalence of HHV-7 in the human population.

 

Source: Secchiero P, Berneman ZN, Gallo RC, Lusso P. Biological and molecular characteristics of human herpesvirus 7: in vitro growth optimization and development of a syncytia inhibition test. Virology. 1994 Jul;202(1):506-12. http://www.ncbi.nlm.nih.gov/pubmed/8009865

 

Human herpesvirus-7 (HHV-7)

Abstract:

HHV-7 first isolated in 1990 from a healthy individual, is a ubiquitous agent. The second independent isolation of HHV-7 from a chronic fatigue syndrome patient was reported in 1992. The seroepidemiology of HHV-7 suggested that its prevalence rate in the U.S.A. population is > 85%; however, in Japan a low prevalence rate has been reported. HHV-7 can be more readily isolated from the saliva than HHV-6. The primary infection of HHV-7 appears later in life than HHV-6. No disease has been reported that is etiologically linked to HHV-7. HHV-7 is more closely related to HHV-6 and the human cytomegalovirus than other members of the human herpesvirus family.

 

Source: Ablashi DV, Berneman ZN, Kramarsky B, Asano Y, Choudhury S, Pearson GR. Human herpesvirus-7 (HHV-7). In Vivo. 1994 Jul-Aug;8(4):549-54. http://www.ncbi.nlm.nih.gov/pubmed/7893982