Tag: persistent viral infection

Detection of herpes viruses in patients with myalgic encephalomyelitis /chronic fatigue syndrome in Belarus

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial chronic disease. The etiology and pathogenesis of ME/CFS are unknown. There are many theories for the occurrence of this disease. but the most convincing is the infectious or viral theory of the emergence of CFS.

The aim of this study is to detect of herpes viruses 6, 7 types and Epstein-Barr  to examine the prevalence HHV-6, HHV-7 and EBV infections in Belarus CFS patients.

We examined 30 patients with CFS in whom fatigue during  more than 2 years (7), more than 1 year (11) and more than 6 months (12). The diagnosis was made on clinical grounds using the Fukuda criteria.

The presence of markers the active forms  infection HHV-6 and HHV-7 in CFS patients with a long period of fatigue  were detected in 16.6% and 26.6% respectively. IgM  antibodies to HHV-6 and EBV. positive, in 16.6% and 6.7% respectively in patients with long-term illness. Detection of IgG antibodies indicates a quiet carrier state, latent phase.

Source: ORLOVA, Svetlana et al. Detection of herpes viruses in patients with myalgic encephalomyelitis /chronic fatigue syndrome in Belarus. Polish Journal of Applied Sciences, [S.l.], v. 6, n. 2, p. 50-53, dec. 2021. ISSN 2451-1544. Available at: <https://pjas.pwsip.edu.pl/index.php/pjas/article/view/176>. Date accessed: 10 jan. 2022. doi: https://doi.org/10.34668/PJAS.2020.6.2.08. (Full text)

The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease with huge social-economic impact. It has been suggested that immune dysregulation, nitrooxidative stress, and metabolic impairment might contribute to disease pathogenesis. However, the etiology of ME/CFS remains largely unclear, and diagnostic/prognostic disease markers are lacking. Several long noncoding RNAs (lncRNA, > 200 bp) have been reported to play roles in immunological diseases or in stress responses.

Methods: In our study, we examined the expression signature of 10 very long lncRNAs (> 5 kb, CR933609, His-RNA, AK124742, GNAS1-AS, EmX2OS, MIAT, TUG1, NEAT1, MALAT1, NTT) in the peripheral blood mononuclear cells of 44 ME/CFS patients.

Results: LncRNAs NTT, MIAT and EmX2OS levels were found to be significantly elevated in ME/CFS patients as compared with healthy controls. Furthermore, NTT and EmX2OS levels increased with disease severity. Stimulation of human monocytic cell line THP-1 and glioma cell line KALS1 with H2O2 (oxidative stress) and poly (I:C) (double strand RNA, representing viral activation) increased the expression levels of NTT and MIAT.

Conclusions: Our study revealed a ME/CFS-associated very long lncRNA expression signature, which might reflect the regulatory response in ME/CFS patients to oxidative stress, chronic viral infection and hypoxemia. Further investigations need to be done to uncover the functions and potential diagnostic value of these lncRNAs in ME/CFS.

Source: Yang CA, Bauer S, Ho YC, Sotzny F, Chang JG, Scheibenbogen C. The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2018 Aug 17;16(1):231. doi: 10.1186/s12967-018-1600-x. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x (Full article)

Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability.

METHODS: Immunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups.

RESULTS: CFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals.

CONCLUSIONS: Our findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS.

 

Source: Curriu M, Carrillo J, Massanella M, Rigau J, Alegre J, Puig J, Garcia-Quintana AM, Castro-Marrero J, Negredo E, Clotet B, Cabrera C, Blanco J. Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome. J Transl Med. 2013 Mar 20;11:68. doi: 10.1186/1479-5876-11-68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614537/ (Full article)

 

Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57) detects active infection in patients with chronic fatigue syndrome

Abstract:

AIMS: To investigate whether the use of recombinant early antigens for detection of antibodies to human cytomegalovirus (HCMV) gene products CM(2) (UL44, UL57) and p52 (UL44) is specific in the diagnosis and differentiation of active HCMV infection in a subset of patients with chronic fatigue syndrome (CFS), a diagnosis which is often missed by the current ELISA assay that uses crude viral lysate antigen.

METHODS: At a single clinic from 1999 to 2001, a total of 4774 serological tests were performed in 1135 patients with patients using two immunoassays, Copalis and ELISA. The Copalis immunoassay utilised HCMV early gene products of UL44 and UL57 recombinant antigens for detection of HCMV IgM antibody, and viral capsid antigen for detection of HCMV IgG antibody. The ELISA immunoassay utilised viral crude lysate as antigen for detection of both HCMV IgG and IgM.

RESULTS: 517 patients (45.6%) were positive for HCMV IgG by both assays. Of these, 12 (2.2%) were positive for HCMV(V) IgM serum antibody by HCMV ELISA assay, and 61 (11.8%) were positive for IgM HCMV serum antibody by Copalis assay. The Copalis assay that uses HCMV early recombinant gene products CM(2) (UL44, UL57) and p52 (UL44) in comparison with ELISA was 98% specific.

CONCLUSIONS: Immunoassays that use early antigen recombinant HCMV CM(2) and p52 are five times more sensitive than HCMV ELISA assay using viral lysate, and are specific in the detection and differentiation of active HCMV infection in a subset of patients with CFS.

 

Source: Beqaj SH, Lerner AM, Fitzgerald JT. Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57) detects active infection in patients with chronic fatigue syndrome. J Clin Pathol. 2008 May;61(5):623-6. Epub 2007 Nov 23. https://www.ncbi.nlm.nih.gov/pubmed/18037660

 

Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence

Abstract:

Since conducting follow-up studies of patients with acute symptomatic parvovirus B19 infection which showed that a significant proportion of patients develop prolonged arthritis and chronic fatigue syndrome (CFS), we have become interested in the mechanisms of this phenomenon. We showed that these cases have high levels of pro-inflammatory cytokines in their circulation and that this correlates with the symptoms. However, the underlying mechanisms were not apparent, and we have used various approaches to begin studying this phenomenon.

DNA polymorphisms were looked for and several were shown to be more common in these subjects compared with controls; these occur within genes of both the immune response [human leucocyte antigen (HLA)-DRB1, HLA-B, transforming growth factor (TGF)-beta1] and those involved in several other cellular functions (predominantly the cytoskeleton and cell adhesion). Interestingly, one particular single-nucleotide polymorphism (SNP) which is associated with symptomatic B19 infection occurs in the Ku80 gene which has recently been shown to be a B19 co-receptor. B19 persistence is probably the key to this phenomenon, and some new data are presented on short regions of sequence homology (17-26 bp) between human, mouse and rat parvoviruses and their respective hosts which occur in many host genes. This homology may provide a foothold for virus persistence and may also play a role in the genesis of disease through gene disruption.

Finally, we used microarrays and TaqMan real-time polymerase chain reaction in 108 normal persons to study human gene expression in persons who are B19-seropositive versus B19-seronegative (age- and sex-matched) to examine the hypothesis that gene regulation may be altered in subjects harbouring the B19 virus DNA. Six genes were found to be differentially expressed with roles in the cytoskeleton (SKIP, MACF1, SPAG7, FLOT1), integrin signalling (FLOT1, RASSF5), HLA class III (c6orf48), and tumour suppression (RASSF5). These results have implications not only for B19 but also for other persistent viruses as well and confirmation is required.

In conclusion, these disparate findings contribute to our understanding of the pathogenesis of B19 disease. We are using these studies as a starting point to study the phenomenon of chronic immune activation following B19 infection.

 

Source: Kerr JR. Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence. J Vet Med B Infect Dis Vet Public Health. 2005 Sep-Oct;52(7-8):335-9. http://www.ncbi.nlm.nih.gov/pubmed/16316396

 

Enterovirus infections in new disguise

Abstract:

Enteroviruses (Coxsackie A and B, echovirus, poliovirus) belong to a group of small RNA-viruses, picomavirus, which are widespread in nature. Enteroviruses cause a number of well known diseases and symptoms in humans, from subclinical infections and the common cold to poliomyelitis with paralysis. The development of polio vaccines is the greatest accomplishment within the field of enterovirus research and the background work was awarded the Nobel prize in 1954. New knowledge implies that enteroviruses play a more important part in the morbidity panorama than was previously thought. Chronic (persistent) enteroviruses were formerly unknown.

Serologic and molecular biology techniques have now demonstrated that enteroviral genomes, in certain situations, persist after the primary infection (which is often silent). Persistent enteroviral infection or recurrent infections and/or virus-stimulated autoimmunity might contribute to the development of diseases with hitherto unexplained pathogenesis, such as post polio syndrome, dilated cardiomyopathy, juvenile (type 1) diabetes and possibly some cases of chronic fatigue syndrome.

 

Source: Fohlman J, Friman G, Tuvemo T. Enterovirus infections in new disguise. Lakartidningen. 1997 Jul 9;94(28-29):2555-60. [Article in Swedish] http://www.ncbi.nlm.nih.gov/pubmed/9254324

 

GPs’ attitudes to a self diagnosis of myalgic encephalomyelitis. Evidence supports presence of encephalitis

Comment on: General practitioners’ attitudes to patients with a self diagnosis of myalgic encephalomyelitis. [BMJ. 1995]

 

EDITOR,-Although the precise pathoaetiology of myalgic encephalomyelitis remains the subject of debate, Shonagh Scott and colleagues are incorrect in asserting that “no evidence exists” of encephalitis. Buchwald et al carried out a large cohort study in which neurological symptoms, results of magnetic resonance imaging, and lymphocyte phenotyping suggested that the patients were experiencing “a chronic, immunologically mediated inflammatory process of the central nervous system.”2 More recently, Schwartz et al, who used single photon emission computed tomography, described abnormalities that were consistent with the hypothesis that “a chronic viral encephalitis” may be present.3 Furthermore, in the only postmortem study to have been published the polymerase chain reaction showed enteroviral sequences (compatible with coxsackie virus B3) in samples from the hypothalamus and brain stem,4 indicating that viral persistence within selective parts of the central nervous system may also play a part.

Given the uncertainties surrounding both the pathoaetiology and the diagnostic criteria for myalgic encephalomyelitis, it is not surprising to learn that self diagnosis produces difficulties in the doctor-patient relationship. The conclusions of and motives behind Scott and colleagues’ study must, however, be questioned in view of the fact that the fictitious patients had a list of vague symptoms that failed to satisfy diagnostic criteria for either a chronic fatigue syndrome (as defined by the International Chronic Fatigue Syndrome Study Group)5 or a postinfectious fatigue syndrome (as defined by current British criteria).6 Neither did the symptoms accord with those that patient support organisations would agree constitute a satisfactory diagnosis of myalgic encephalomyelitis.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2549699/pdf/bmj00593-0058b.pdf

 

Source: Shepherd C. GPs’ attitudes to a self diagnosis of myalgic encephalomyelitis. Evidence supports presence of encephalitis. BMJ. 1995 May 20;310(6990):1330. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2549699/

 

Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome

Abstract:

Levels of 2′,5′-oligoadenylate (2-5A) synthetase, bioactive 2-5A, and RNase L were measured in extracts of peripheral blood mononuclear cells (PBMCs) from 15 individuals with chronic fatigue syndrome (CFS) before and during therapy with the biological response modifier poly(I).poly(C12U) and were compared with levels in healthy controls.

Patients differed significantly from controls in having a lower mean basal level of latent 2-5A synthetase (P < .0001), a higher pretreatment level of bioactive 2-5A (P = .002), and a higher level of pretherapy RNase L activity (P < .0001). PBMC extracts from 10 persons with CFS had a mean basal level of activated 2-5A synthetase higher than the corresponding control value (P = .009). All seven pretherapy PBMC extracts tested were positive for the replication of human herpesvirus 6 (HHV-6).

Therapy with poly(I).poly(C12U) resulted in a significant decrease in HHV-6 activity (P < .01) and in downregulation of the 2-5A synthetase/RNase L pathway in temporal association with clinical and neuropsychological improvement. The upregulated 2-5A pathway in CFS before therapy is consistent with an activated immune state and a role for persistent viral infection in the pathogenesis of CFS. The response to therapy suggests direct or indirect antiviral activity of poly(I).poly(C12U) in this situation.

 

Source: Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Müller WE, Schröder HC, Carter WA, et al. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S96-104. http://www.ncbi.nlm.nih.gov/pubmed/8148461

 

Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome

Abstract:

AIMS: To investigate in detail various biochemical and pathophysiological indices of muscle pathology in acute onset post-viral fatigue syndrome (PVFS).

METHODS: Twenty three patients with PVFS (of mean duration 4.6 years) were subjected to needle biopsy for histomorphometry and total RNA contents. Plasma analysis included serology and creatine kinase activities. Indices of whole body mass were also measured–namely, whole body potassium content and plasma carnosinase activities.

RESULTS: About 80% of the patients had serology indicative of persistent enteroviral infection as determined by VP1 antigen assay. Only about 10% of that same group of patients had serological indications of current enterovirus infection by IgM assay; a separate subset of 10% showed antibody changes suggestive of reactivation of Epstein-Barr virus. Quantitative morphometric analysis of skeletal muscle fibres indicated that the quadriceps muscle was normal or displayed only minor abnormalities in 22 patients. The Quetelet’s Index (body mass index) and whole-body potassium values (index of lean body mass) were not affected in PVFS. The mean plasma carnosinase and creatinine kinase activities were also generally normal in these patients. The mean muscle RNA composition–mg RNA/mg DNA: was significantly reduced in acute onset PVFS by about 15%. The protein:DNA ratio was not significantly affected.

CONCLUSIONS: Patients with acute onset PVFS, therefore, lose muscle protein synthetic potential, but not muscle bulk. Histopathology is consistent with these observations. These perturbations may contribute to the apparent feature of perceived muscle weakness associated with the persistent viral infection in the muscle themselves.

 

Source: Preedy VR, Smith DG, Salisbury JR, Peters TJ. Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome. J Clin Pathol. 1993 Aug;46(8):722-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC501456/