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

 

Severe chronic active Epstein-Barr virus infection syndrome and adenovirus type-2 infection

Abstract:

Four patients from 4 to 24 years of age (3 males, 1 female) with generalized lymphadenopathy, hepatosplenomegaly, and intermittent fever associated with chronic active Epstein-Barr virus (EBV) infection were investigated.

Laboratory data showed polyclonal gammopathy and a tendency for bone marrow suppression. Noteworthy were the extremely elevated immunoglobulin G (IgG) antibody titers to Epstein-Barr viral capsid antigen (VCA) (range, 10,240-81,920) and early antigen (EA) (range, 1,280-40,960). All patients had IgA antibodies to VCA and EA. Subtle, heterogeneous immune functional defects were observed in all four patients. Another unusual feature was our inability to establish spontaneous or B95-8 EBV-immortalized lymphoblastoid cell lines (LCLs) due to a marked cytopathic effect (CPE). Thus, we investigated for other viruses.

Both IgG and IgM antibodies to adenovirus type-2 (Ad-2) were positive by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) test, suggesting recent or activated Ad-2 infection had occurred. Dual active EBV and Ad-2 infections were likely etiologic in this severe chronic active EBV infection syndrome.

 

Source: Okano M, Thiele GM, Purtilo DT. Severe chronic active Epstein-Barr virus infection syndrome and adenovirus type-2 infection. Am J Pediatr Hematol Oncol. 1990 Summer;12(2):168-73. http://www.ncbi.nlm.nih.gov/pubmed/2165745

 

Patient management of post-viral fatigue syndrome

Abstract:

A case definition for post-viral fatigue syndrome is proposed within which various subgroups of patients exist. Any one treatment may not apply to all the subgroups. In particular, patients’ experiences do not show that avoidance of exercise is maladaptive. It is proposed that the recently ill often try to exercise to fitness whereas the chronically ill have learnt to avoid exercise. Recovery is more likely to be achieved if patients learn about their illness and do not exhaust their available energy.

 

Source: Ho-Yen DO. Patient management of post-viral fatigue syndrome. Br J Gen Pract. 1990 Jan;40(330):37-9. http://www.ncbi.nlm.nih.gov/pubmed/2107839

Note: You may read the full article here:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1371214/

 

Usefulness of a standard battery of laboratory tests in investigating chronic fatigue in adults

Abstract:

Twenty-two adults with chronic fatigue were studied to determine the clinical usefulness of commonly applied laboratory tests. Subjects with the chief complaint of fatigue persisting for more than one year were followed for an average of seven months at a university family health centre.

During this time a group of commonly recommended tests were carried out and the patients had repeated physical examinations. Physical diseases and laboratory abnormalities were few, and patients with abnormal values and active problems were followed until their fatigue resolved or their abnormalities reverted to normal following therapy. The study demonstrated that the presence of an abnormal laboratory result in a fatigued individual does not necessarily indicate the cause of fatigue.

A psychiatric history was also performed and patients were tested with the symptom check list 90-R (SCL-90-R), a 90-item psychological symptom check list. Seven patients were receiving psychotherapy when they enrolled in the study. Two additional subjects entered therapy after the start of the study. Results on the symptom check list for the study group were largely abnormal, with a majority scoring in the highest quartile for depression, paranoid ideation and psychoticism.

It is concluded that the investigation of patients with fatigue which has lasted for longer than one year should focus on psychological causes. In this group of patients laboratory abnormalities are not useful in guiding evaluation or treatment for their fatigue.

 

Source: Valdini A, Steinhardt S, Feldman E. Usefulness of a standard battery of laboratory tests in investigating chronic fatigue in adults. Fam Pract. 1989 Dec;6(4):286-91. http://www.ncbi.nlm.nih.gov/pubmed/2632306

 

Postviral syndrome–how can a diagnosis be made? A study of patients undergoing a Monospot test

Abstract:

Eighty-nine of 150 patients having a Monospot test filled out a questionnaire about their illness, and the General Health Questionnaire. They completed a follow-up questionnaire 6 months later.

Twelve (8%) had a positive Monospot. Twenty-eight of 83 serum samples tested (34%) were positive for VP1 enteroviral antigen. Forty of the patients had a self limiting illness, 13 had a definite diagnosis (excepting glandular fever), 14 had a possible postviral syndrome, 10 had recurrent sore throats/flu, and 12 had a chronic non-specific illness.

Patients with a specific diagnosis were less likely to complain of aching muscles/joints, sore throat, tiredness or loss of concentration. Their GHQ scores were lower, although this just failed to reach significance (P = 0.08), and they scored significantly lower on the somatic symptoms subscale (P = 0.022). Overall 72% scored above the GHQ threshold for ‘psychological caseness’ which is higher than in other studies. Sixty-five per cent of the sample questioned at 6 months felt that their illness started with a viral infection.

The methodological problems involved in making a diagnosis of postviral syndrome are discussed.

 

Source:  Bowman SJ, Brostoff J, Newman S, Mowbray JF. Postviral syndrome–how can a diagnosis be made? A study of patients undergoing a Monospot test. J R Soc Med. 1989 Dec;82(12):712-6. http://www.ncbi.nlm.nih.gov/pubmed/2614761

Note: You may read the full article here:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292411/

 

A flight surgeon’s personal view of an emerging illness

Abstract:

The personal experience of a retired Air Force flight surgeon and instrument-rated civilian pilot with an illness that has achieved recent prominence in both the popular and medical press is recounted. The author believes that the illness is widely prevalent and its incidence is increasing. His experience and conviction is that, during certain phases of the illness, both cognitive dysfunction and orthostatic intolerance occur that can pose grave safety risks in the aviation environment, and must be taken seriously by the practicing flight surgeon. As in all emerging illnesses, clinical experience and judgment must precede more definitive proof of the effects of this illness.

 

Source: Harvey WT. A flight surgeon’s personal view of an emerging illness. Aviat Space Environ Med. 1989 Dec;60(12):1199-201. http://www.ncbi.nlm.nih.gov/pubmed/2604676

 

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

 

Myalgic encephalomyelitis: postviral fatigue and the heart

Note: This letter appeared in the November 11, 1989 issue of the British Medical Journal.

 

SIR, The controversial subject of myalgic encephalomyelitis has surfaced once more,(1) and I would like to contribute to the debate about its viral origins.

Persistent virus infections impair the specialised functions of cells. These include the synthesis of specific products such as heavy and light myosin chains, melanin, hormones, and immune functions.(2) Evidence of persistent enterovirus infection has been found in both dilated cardiomyopathy,(3-5) an organic disease discussed at a recent symposium,(3) and the more controversial myalgic encephalomyelitis.(6,7)

In murine myocarditis induced by Coxsackie viruses, more severe and lasting disease is associated with immunopathological processes, which include virus specific, cross reactive, and autoimmune reactions.(3, 8, 9) In Coxsackie viral myocarditis and cardiomyopathy of humans the antibodies that cross react with Coxsackie B antigens are reported.(3) Serum samples from patients with.cardiomyopathy may react with cardiac ,B adrenoreceptors, with mitochondrial ADP/ATP carriers, and with cell surface protein of the calcium channel causing calcium overload of myocytes and consequent dysfunction.(3) Thus a complex pattern of pathogenic mechanisms is emerging to explain dilated cardiomyopathy, which was formerly considered to be idiopathic but is now recognised as a late sequel of a proportion of cardiac infections with certain enteroviruses, particularly those of the Coxsackie B group. This does not exclude the possible role of other viruses-for example, arboviruses where these are prevalent-as initiators of such pathogenic processes.

It seems likely that similar immunological and metabolic disturbances in myalgic encephalomyelitis may also result from chronic infection, usually with enteroviruses, providing the organic basis of the postviral fatigue syndrome.(10) This condition is characterised by severe fatiguability and recuperation through rest. The myocardium, however, cannot rest-except terminally. Does “postviral dilated cardiomyopathy” represent the result of postviral fatigue syndrome of the unresting heart?

~NORMAN R GRIST Communicable Diseases (Scotland) Unit, Ruchill Hospital, Glasgow G20 9NB

 

References

1 Harris F, Taitz LS. Damaging diagnoses of myalgic encephalitis in children. BrMedj 1989;299:790. (23 September.)

2 Southern P, Oldstone MBA. Medical consequences of persistent viral infection. N Englj Med 1986;314:359-67.

3 Schultheiss HP, ed. New concepts in viral heart disease. Berlin: Springer, 1988.

4 Bowles NE, Richardson PJ, Olsen EGJ, Archard LC. Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet 1986;i: 1120-3.

5 Kandolf R, Kirschner P, Amies D, et al. Enteroviral heart disease: diagnosis by in situ hybridization. In: Schultheiss HP, ed. New concepts in viral heart disease. Berlin: Springer, 1988:337-48.

6 Yousef GE, Mann GF, Smith DG, et al. Chronic enterovirus infection in patients with postviral fatigue syndrome. Lancet 1988;i: 146-50.

7 Archard LC, Bowles NE, Behan PO, Bell EJ, Doyle D. Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatinine kinase. J R Soc Med 1988;81:326-9.

8 Huber SA. The role of immune mechanisms in pathogenesis. In: Bendinelli M, Friedman H, eds. Coxsackieviruses, a general update. New York: Plenum, 1988:103-16.

9 Beisel KW, Rose NR. Relationship of coxsackievirus to cardiac autoimmnunity. In: Bendinelli M, Friedmann H, eds. Coxsackievinruses, a general update. New York: Plenum, 1988:271-92.

10 Behan PO, Behan WMH, Bell EJ. The post-viral fatigue syndrome-an analysis of the findings in 50 cases. J Infect 1985;10:21 1-22.

 

Source:  N. R. Grist. Myalgic encephalomyelitis: postviral fatigue and the heart. BMJ. 1989 Nov 11; 299(6709): 1219. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1838100/pdf/bmj00258-0049b.pdf

 

The chronic fatigue syndrome: definition, current studies and lessons for fibromyalgia research

Abstract:

Chronic fatigue syndrome (CFS) is characterized by chronic, debilitating fatigue lasting greater than 6 months. Frequent chronic and recurrent findings include fever, pharyngitis, myalgias, adenopathy, arthralgias, difficulties in cognition and disorders of mood. In the majority of patients, the illness starts suddenly with an acute, “flu-like” illness.

The following laboratory abnormalities are seen with some frequency, although none are seen in all patients: lymphocytosis, atypical lymphocytosis, monocytosis, elevation of hepatocellular enzymes, low levels of antinuclear antibodies, varying levels of antithyroid antibodies, partial hypergammaglobulinemia, elevated CD4:CD8 ratio, decreased cytolytic activity of natural killer cells, and low levels of immune complexes. Clinical and serologic studies suggest an association of CFS with all of the human herpesviruses, particularly Epstein-Barr virus (EBV) and the recently discovered human B lymphotropic virus (HBLV) or human herpesvirus 6; neither EBV nor HBLV has yet been shown to play a causal role in the illness.

Preliminary evidence suggests that many of these features of CFS also are seen in patients with fibromyalgia.

 

Source: Komaroff AL, Goldenberg D. The chronic fatigue syndrome: definition, current studies and lessons for fibromyalgia research. J Rheumatol Suppl. 1989 Nov;19:23-7. http://www.ncbi.nlm.nih.gov/pubmed/2691680

 

Nonrestorative sleep and symptoms after a febrile illness in patients with fibrositis and chronic fatigue syndromes

Abstract:

This review summarizes the physiologic and clinical evidence that shows nonrestorative sleep to be associated with chronic fatigue and diffuse myalgia after a flulike illness. Such a febrile illness may trigger alteration in sleep-wake brain and immune functions in patients with fibrositis or chronic fatigue syndromes.

 

Source: Moldofsky H. Nonrestorative sleep and symptoms after a febrile illness in patients with fibrositis and chronic fatigue syndromes. J Rheumatol Suppl. 1989 Nov;19:150-3. http://www.ncbi.nlm.nih.gov/pubmed/2691676