Tag: HHV6

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

 

Chronic fatigue in children: clinical features, Epstein-Barr virus and human herpesvirus 6 serology and long term follow-up

Abstract:

During a 2-year period, 23 patients (14 girls, 9 boys) with chronic fatigue were referred to the Pediatric Infectious Disease Clinic of a tertiary care center, representing 19% of all out-patients seen in that clinic during that time. The median age was 14 years and the median duration of symptoms before referral was 6 months; 65% had missed at least 2 weeks of school and 30% required a home tutor.

There were few positive physical findings and no elevation of white blood cell count (median, 7000/mm3) or erythrocyte sedimentation rate (median, 5 mm/hour). Twenty-five percent had no evidence of Epstein-Barr virus infection, 15% had current or recent infection and 60% had past infection; 33% of the latter had detectable antibody to early antigen but the titers were low. Human herpesvirus 6 titers in 8 patients were similar to those in age- and sex-matched controls.

Of 17 patients contacted after a median of 26 months, 76% reported definite improvement, although 38% of these still experienced occasional symptoms. In this referral population chronic fatigue was a common presenting complaint, was associated with marked degrees of dysfunction and bore no relationship to Epstein-Barr virus or human herpesvirus 6 infection. In most children the disorder was self-limited, although a minority were persistently or severely affected.

 

Source: Marshall GS, Gesser RM, Yamanishi K, Starr SE. Chronic fatigue in children: clinical features, Epstein-Barr virus and human herpesvirus 6 serology and long term follow-up. Pediatr Infect Dis J. 1991 Apr;10(4):287-90. http://www.ncbi.nlm.nih.gov/pubmed/1648198

 

A comprehensive immunological analysis in chronic fatigue syndrome

Abstract:

A detailed analysis of cell-mediated and antibody-mediated immunity was performed in 20 CDC-defined patients with chronic fatigue syndrome (CFS) and 20 age- and sex-matched healthy controls.

CD3+, CD4+, CD8+, and CD20+ lymphocytes were comparable in two groups. Natural killer cells as defined by CD16, CD56 and CD57 antigens were significantly reduced in CFS. A significant increase in the proportions of CD4+ ICAM 1+ T cells was observed in CFS. Monocytes from CFS displayed increased density (as determined by mean fluorescence channel numbers) of intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function associated antigen 1 (LFA-1), but showed decreased enhancing response to recombinant interferon-gamma in vitro.

The lymphocyte DNA synthesis in response to phytohaemoglobulin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) was normal but the response to soluble antigens was significantly reduced. Serum IgM, IgG, IgA, and IgG subclasses were normal. In vivo specific antibody response to pneumococcus vaccine was depressed in CFS.

Forty percent of patients showed titres of anti-human herpes virus 6 (anti-HHV-6) antibody higher than that in the controls (greater than or equal to 1/80). These data suggest immunological dysfunction in patients with chronic fatigue syndrome. The significance of these observations is discussed.

 

Source: Gupta S, Vayuvegula B. A comprehensive immunological analysis in chronic fatigue syndrome. Scand J Immunol. 1991 Mar;33(3):319-27. http://www.ncbi.nlm.nih.gov/pubmed/1849315

 

Chronic fatigue syndrome in northern Nevada

Abstract:

The clinical and laboratory findings from studies of patients with chronic fatigue syndrome (CFS) from northern Nevada are summarized. Physicians caring for these patients have estimated that greater than 400 patients with CFS from northern Nevada and nearby communities in California were identified between 1984 and 1988.

As a result of these studies, a cluster of clinical and laboratory features associated with the illness in moderately to severely affected patients has been identified: profound fatigue of prolonged duration; cervical lymphadenopathy; recurrent sore throat and/or symptoms of influenza; loss of cognitive function manifested by loss of memory and loss of ability to concentrate; myalgia; impairment of fine motor skills; abnormal findings on magnetic resonance imaging brain scan; depressed level of antibody to Epstein-Barr virus (EBV) nuclear antigen; elevated level of antibody to EBV early antigen restricted component; elevated ratio of CD4 helper to CD8 suppressor cells; and strong evidence of association of this syndrome with infection with human herpesvirus 6.

More-serious and longer-lasting neurologic impairments, including seizures, psychosis, and dementia, have also been observed in some of these patients.

 

Source: Daugherty SA, Henry BE, Peterson DL, Swarts RL, Bastien S, Thomas RS. Chronic fatigue syndrome in northern Nevada. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S39-44. http://www.ncbi.nlm.nih.gov/pubmed/1850542

 

Electrophoretic analysis of human herpesvirus 6 polypeptides immunoprecipitated from infected cells with human sera

Abstract:

Proteins of human herpesvirus 6 (HHV-6) eliciting human antibody responses were examined in serum from healthy adults and patients with AIDS, chronic fatigue syndrome, Hodgkin’s disease, and Sjögren’s syndrome.

HHV-6 IgG antibody titers measured by immunofluorescence (IF) ranged from 1:10 to 1:1280. Lysates of HHV-6-infected and uninfected cells labeled with [35S]methionine, [3H]glucosamine, and 125I were immunoprecipitated with sera and analyzed electophoretically. Sera with IF titers greater than or equal to 1:20 immunoprecipitated greater than 20 [35S]methionine-labeled HHV-6 polypeptides of approximately 26-180 kDa.

At least 10 HHV-6 glycoproteins and 8 HHV-6 polypeptides associated with the surfaces of infected cells were recognized by human sera. The approximate molecular masses of glycoproteins immunoprecipitated by human sera were similar to those immunoprecipitated by monoclonal antibodies.

The labeling intensity of HHV-6 protein bands increased with increasing IF titer, and the effect was most prominent for HHV-6 glycopolypeptides. No reactivities with specific HHV-6 polypeptide(s) were characteristic of a given patient group.

These findings suggest that HHV-6 glycoproteins are good targets for human antibody responses.

 

Source: Balachandran N, Tirawatnapong S, Pfeiffer B, Ablashi DV, Salahuddin SZ. Electrophoretic analysis of human herpesvirus 6 polypeptides immunoprecipitated from infected cells with human sera. J Infect Dis. 1991 Jan;163(1):29-34. http://www.ncbi.nlm.nih.gov/pubmed/1845808

 

A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6

Abstract:

A 17-year-old, previously healthy woman developed an acute “mononucleosis-like” illness with an associated “atypical” pneumonitis, followed by years of debilitating chronic fatigue, fevers, a 10-kg weight loss, night sweats, and neurocognitive symptoms. Thereafter, her sister developed a similar but less severe illness.

The patient developed marked, chronic lymphadenopathy and splenomegaly, with associated persistent relative lymphocytosis and atypical lymphocytosis and with thrombocytopenia. After 3 years of illness, a splenectomy was performed, which resulted in some symptomatic improvement, prompt weight gain, and resolution of all hematologic abnormalities. Serial immunologic studies revealed a strikingly elevated number of activated B lymphocytes and a T lymphopenia, which improved but did not return to normal postsplenectomy. No causal association was found with any of several infectious agents that could produce such a lymphoproliferative illness.

However, both the patient and her sister had evidence of active infection with the recently discovered human herpesvirus-6. Seven years after the onset of the illness, the patient and her sister remain chronically ill.

 

Source:  Buchwald D, Freedman AS, Ablashi DV, Sullivan JL, Caligiuri M, Weinberg DS, Hall CG, Ashley RL, Saxinger C, Balachandran N, et al. A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6. J Clin Immunol. 1990 Nov;10(6):335-44. http://www.ncbi.nlm.nih.gov/pubmed/1964694

 

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

 

Chronic fatigue syndrome

Abstract:

Reports on conditions of chronic fatigue associated with other somatopsychic symptoms after acute viral infections have led to the hypothesis of a “chronic fatigue syndrome” (CFS). Historical disease descriptions, like e.g. “myalgic encephalomyelitits”, were updated by means of modern virological diagnostic techniques and data analysis.

Several viral agents like enteroviruses, Epstein-Barr virus, Human-Herpesvirus 6 and other herpesviruses have been implicated for possible underlying infections. A preliminary disease definition by the Center for Disease Control (CDC) seeks to provide a rational basis for further etiological studies. In fact, there is growing consensus that the syndrome comprises various separate disease entities and causative agents.

Today we can tentatively differentiate a “chronic mononucleosis” after infection with Epstein-Barr virus, an etiologically undetermined “postviral fatigue syndrome” and a fatigue syndrome of the myalgic type after Coxsackie-B virus infection. Furthermore, a valid diagnosis of CFS must be based on the exclusion of defined other diseases and the awareness of dealing with a hypothetical concept. As a result, current knowledge does not yet allow specific therapeutic recommendations.

 

Source: Ewig S, Dengler HJ. Chronic fatigue syndrome. Klin Wochenschr. 1990 Aug 17;68(16):789-96. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/2170741

 

Isolation of human herpesvirus-6 from clinical specimens using human fibroblast cultures

Abstract:

The isolation and characterization of human herpesvirus-6 (HHV-6) has been hindered by the lack of cell lines useful for its rapid propagation. Recently, we have reported that the MRC-5 cell line (human diploid lung fibroblasts) was susceptible for HHV-6 infection.

In this study, we report on the isolation of HHV-6 from the peripheral blood or buffy coat of three chronic fatigue syndrome patients, one post-liver transplant patient, and one severe chronic active Epstein-Barr virus syndrome patient using the MRC-5 cell line.

Additionally, it was observed by Southern blot hybridization studies that four of five isolates had different restriction enzyme fragment patterns than the isolate obtained from the National Institutes of Health with Eco RI.

These data suggest the usefulness of the MRC-5 cell line in the isolation and characterization of HHV-6 from various patients.

 

Source: Luka J, Okano M, Thiele G. Isolation of human herpesvirus-6 from clinical specimens using human fibroblast cultures. J Clin Lab Anal. 1990;4(6):483-6. http://www.ncbi.nlm.nih.gov/pubmed/2178187

 

What’s new in human herpesvirus-6? Clinical immunopathology of the HHV-6 infection

Abstract:

Human herpesvirus-6 (HHV-6), formerly known as human B-lymphotropic virus (HBLV), was first isolated in 1986 from patients with lymphoproliferative disorders and AIDS. Antibody prevalence against HHV-6 varies between about 60-80% indicating a widespread latent infection.

Although HHV-6 infects in vivo primarily T-lymphocytes, it is associated with similar diseases as in infection with Epstein-Barr virus (EBV), a clearly B-lymphotropic virus. Reactivation of latent HHV-6 infection in patients with subnormal host defense may cause persistent active infection with so-called postinfectious chronic fatigue syndrome (PICFS) or may contribute to other pathologies such as immune deficiency itself, autoimmune disorders or progressive lymphoproliferation.

Coinfection of CD4 cells by HHV-6 and human immunodeficiency virus (HIV 1) in AIDS patients can aggravate HIV-induced acquired immune deficiency. These characteristics of the only recently detected new virus justify further intense investigation.

 

Source: Krueger GR, Sander C.  What’s new in human herpesvirus-6? Clinical immunopathology of the HHV-6 infection. Pathol Res Pract. 1989 Dec;185(6):915-29. http://www.ncbi.nlm.nih.gov/pubmed/2559396