Tag: viral infection

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

Abstract:

Background: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.

Methods: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections’ contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).

Results: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a “moderate association” by Cohen’s d test) compared to both healthy and diseased controls.

Conclusion: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

Source: Hwang, JH., Lee, JS., Oh, HM. et al. Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis. J Transl Med 21, 763 (2023). https://doi.org/10.1186/s12967-023-04635-0 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04635-0 (Full text)

Loss of stress response as a consequence of viral infection: implications for disease and therapy

Abstract:

Herein, we propose that viral infection can induce a deficient cell stress response and thereby impairs stress tolerance and makes tissues vulnerable to damage. Having a valid paradigm to address the pathological impacts of viral infections could lead to effective new therapies for diseases that have previously been unresponsive to intervention. Host response to viral infections can also lead to autoimmune diseases like type 1 diabetes. In the case of Newcastle disease virus, the effects of viral infection on heat shock proteins may be leveraged as a therapy for cancer. Finally, the search for a specific virus being responsible for a condition like chronic fatigue syndrome may not be worthwhile if the disease is simply a nonspecific response to viral infection.

 

Source: Hooper PL, Hightower LE, Hooper PL. Loss of stress response as a consequence of viral infection: implications for disease and therapy. Cell Stress Chaperones. 2012 Nov;17(6):647-55. doi: 10.1007/s12192-012-0352-4. Epub 2012 Jul 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468676/ (Full article)

 

An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue

Abstract:

BACKGROUND: Chronic fatigue syndrome is an idiopathic syndrome widely suspected of having an infectious or immune etiology. We applied an unbiased metagenomic approach to try to identify known or novel infectious agents in the serum of 45 cases with chronic fatigue syndrome or idiopathic chronic fatigue. Controls were the unaffected monozygotic co-twins of cases, and serum samples were obtained at the same place and time.

RESULTS: No novel DNA or RNA viral signatures were confidently identified. Four affected twins and no unaffected twins evidenced viremia with GB virus C (8.9% vs. 0%, p = 0.019), and one affected twin had previously undetected hepatitis C viremia. An excess of GB virus C viremia in cases with chronic fatigue requires confirmation.

CONCLUSIONS: Current, impairing chronic fatigue was not robustly associated with viremia detectable in serum.

 

Source: Sullivan PF, Allander T, Lysholm F, Goh S, Persson B, Jacks A, Evengård B, Pedersen NL, Andersson B. An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue. BMC Microbiol. 2011 Jan 2;11:2. doi: 10.1186/1471-2180-11-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022642/ (Full article)

 

Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: The authors have previously reported genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) based on expression of 88 human genes.

AIM: To attempt to reproduce these findings, determine the specificity of this signature to CFS/ME, and test for associations between CFS/ME subtype and infection.

METHODS: Expression levels of 88 human genes were determined in blood of 62 new patients with idiopathic CFS/ME (according to Fukuda criteria), six patients with Q-fever-associated CFS/ME from the Birmingham Q-fever outbreak (according to Fukuda criteria), 14 patients with endogenous depression (according to DSM-IV criteria) and 29 normal blood donors.

RESULTS: In patients with CFS/ME, differential expression was confirmed for all 88 genes. Q-CFS/ME had similar patterns of gene expression to idiopathic CFS/ME. Gene expression in patients with endogenous depression was similar to that in the normal controls, except for upregulation of five genes (APP, CREBBP, GNAS, PDCD2 and PDCD6). Clustering of combined gene data in CFS/ME patients for this and the authors’ previous study (117 CFS/ME patients) revealed genomic subtypes with distinct differences in SF36 scores, clinical phenotypes, severity and geographical distribution. Antibody testing for Epstein-Barr virus, enterovirus, Coxiella burnetii and parvovirus B19 revealed evidence of subtype-specific relationships for Epstein-Barr virus and enterovirus, the two most common infectious triggers of CFS/ME.

CONCLUSIONS: This study confirms the involvement of these genes in CFS/ME.

 

Source: Zhang L, Gough J, Christmas D, Mattey DL, Richards SC, Main J, Enlander D, Honeybourne D, Ayres JG, Nutt DJ, Kerr JR. Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis. J Clin Pathol. 2010 Feb;63(2):156-64. doi: 10.1136/jcp.2009.072561. Epub 2009 Dec 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921262/ (Full article)

 

Viral infections in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous illness in which patients can have different, overlapping signs and symptoms. No single underlying cause has been established for all CFS patients. Epidemiological studies reveal that a flu-like sickness precedes the onset in the majority of cases. The major hypothesis of the pathogenesis of CFS is that infectious agents such as viruses, may trigger and lead to chronic activation of the immune system with abnormal regulation of cytokine production. Many studies have been performed to identify the possible microbial triggers and to understand the epidemiological microbial agents. We have summarized the recent progressive literature of virus, rickettsia, and mycoplasma implicated in the pathogenesis of CFS.

 

Source: Sairenji T, Nagata K. Viral infections in chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):991-6. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561687

 

A longitudinal study of the relationship between psychological distress and recurrence of upper respiratory tract infections in chronic fatigue syndrome

Abstract:

OBJECTIVES: Previous research has found that chronic fatigue syndrome (CFS) patients report increased susceptibility to upper respiratory tract illnesses (URTIs) when compared with healthy volunteers. This study aimed to replicate and extend this research by investigating the role of psychological distress (stress and negative mood) in the recurrence of URTIs in CFS patients as well as its role in the recurrence of CFS symptoms.

DESIGN: A 15-week diary study.

METHODS: Measures of psychological stress, negative mood, recurrence of URTIs and symptoms were recorded each week for a 15-week period. CFS patients (N=21), who had been assessed and diagnosed according to the Oxford criteria, were recruited from the Cardiff Chronic Fatigue Clinic and compared with a matched group of healthy controls (N=18). Frequency of occurrence of infectious illness and the relationship between psychological stress/negative mood and occurrence of illness were assessed.

RESULTS: CFS patients reported more URTIs than the controls. Stress scores (and negative mood) were significantly higher in the week prior to the occurrence of URTIs than in weeks when no subsequent illness occurred. High levels of psychological stress also preceded the severity of reported symptoms of fatigue in the CFS group.

CONCLUSIONS: CFS patients reported more frequent URTIs than healthy controls and these recurrences were preceded by high levels of psychological stress. High levels of stress were also associated with greater subsequent fatigue. Possible explanations of these results are discussed.

 

Source: Faulkner S, Smith A. A longitudinal study of the relationship between psychological distress and recurrence of upper respiratory tract infections in chronic fatigue syndrome. Br J Health Psychol. 2008 Feb;13(Pt 1):177-86. https://www.ncbi.nlm.nih.gov/pubmed/17535488

 

Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a multisystem disease, the pathogenesis of which remains undetermined.

AIMS: To test the hypothesis that there are reproducible abnormalities of gene expression in patients with CFS compared with normal healthy persons.

METHODS: To gain further insight into the pathogenesis of this disease, gene expression was analysed in peripheral blood mononuclear cells from 25 patients with CFS diagnosed according to the Centers for Disease Control criteria and 25 normal blood donors matched for age, sex, and geographical location, using a single colour microarray representing 9522 human genes. After normalisation, average difference values for each gene were compared between test and control groups using a cutoff fold difference of expression > or = 1.5 and a p value of 0.001. Genes showing differential expression were further analysed using Taqman real time polymerase chain reaction (PCR) in fresh samples.

RESULTS: Analysis of microarray data revealed differential expression of 35 genes. Real time PCR confirmed differential expression in the same direction as array results for 16 of these genes, 15 of which were upregulated (ABCD4, PRKCL1, MRPL23, CD2BP2, GSN, NTE, POLR2G, PEX16, EIF2B4, EIF4G1, ANAPC11, PDCD2, KHSRP, BRMS1, and GABARAPL1) and one of which was downregulated (IL-10RA). This profile suggests T cell activation and perturbation of neuronal and mitochondrial function. Upregulation of neuropathy target esterase and eukaryotic translation initiation factor 4G1 may suggest links with organophosphate exposure and virus infection, respectively.

CONCLUSION: These results suggest that patients with CFS have reproducible alterations in gene regulation.

 

Source: Kaushik N, Fear D, Richards SC, McDermott CR, Nuwaysir EF, Kellam P, Harrison TJ, Wilkinson RJ, Tyrrell DA, Holgate ST, Kerr JR. Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome. J Clin Pathol. 2005 Aug;58(8):826-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770875/ (Full article)

 

Diagnostic evaluation of 2′, 5′-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan

Abstract:

To investigate the association of viral infections with chronic fatigue syndrome (CFS), we assayed 2′, 5′-oligoadenylate synthetase (2-5AS) activities in peripheral blood mononuclear cells from CFS patients in Japan. These patients were diagnosed in two hospitals, H1 and H2, located in different areas of the country.

The activities were detected in 19 (86%) and 7 (32%) of each of the 22 patients in H1 and H2, respectively, while they were detected in only four (11%) out of the 38 healthy controls. IFN-alpha was similarly detected in a few CFS patients and healthy controls.

We also assayed the antibody titers against Epstein-Barr virus (EBV) and Coxiella burnetii in these patients. The EBV anti-EA-IgG antibodies were detected in two (9%) and seven (32%) of each of the 22 patients in H1 and H2, respectively. Anti-C. burnetii IgG antibodies were detected in six (27%) out of 22 patients in H1 but not in 22 patients in H2, while they were detected in one (11%) of the nine healthy controls.

Some CFS patients may be associated with EBV or C. burnetii infection. There were some statistical correlations between the 2-5AS activities and antibody titers of EA-IgG (P < 0.05, Student’s t-test) but not to the antibody titers of C. burnetii. The up-regulation of 2-5AS activities suggests immunological dysfunctions with some virus infections in the CFS patients. Our results indicate that 2-5AS activities are useful for a diagnostic marker of CFS and for exploring the complicated pathogenesis of CFS.

 

Source: Ikuta K, Yamada T, Shimomura T, Kuratsune H, Kawahara R, Ikawa S, Ohnishi E, Sokawa Y, Fukushi H, Hirai K, Watanabe Y, Kurata T, Kitani T, Sairenji T. Diagnostic evaluation of 2′, 5′-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan. Microbes Infect. 2003 Oct;5(12):1096-102. http://www.ncbi.nlm.nih.gov/pubmed/14554250

 

Diverse etiologies for chronic fatigue syndrome

Comment on: Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome. [Clin Infect Dis. 2002]

 

SIR—Koelle et al.  recently studied 22 pairs of identical twins discordant for chronic fatigue syndrome and concluded that there was no major contribution for viral infections in the perpetuation of chronic fatigue syndrome (CFS). The authors should be commended for their methodology and the use of well-matched control subjects. However, the study raised several issues.

First, similar to previous studies, the approach of Koelle et al.  was to look for statistical differences among the well-matched pairs with respect to the presence of viral antibodies and, more specifically, the presence of DNA of the viruses studied. Although these viruses were no more prevalent among the patients with CFS than among their healthy twins, one cannot conclude that these viruses are not the cause of CFS in a small subset of patients. CFS has been described in a small number of patients who had had well-documented acute Epstein-Barr virus (EBV), cytomegalovirus (CMV), and parvovirus B19 infections, and many of the patients responded to specific antiviral therapy. Of the first 200 patients with CFS who we evaluated for viral etiologies , only ∼10% had etiologies that were attributed to the viruses studied by Koelle et al. Chlamydia pneumoniae infection, an uncommon, although treatable, cause of CFS, was also dismissed in a previous, smaller study .

You can read the rest of this comment here: http://cid.oxfordjournals.org/content/36/5/671.long

 

Source: Chia JK, Chia A. Diverse etiologies for chronic fatigue syndrome. Clin Infect Dis. 2003 Mar 1;36(5):671-2; author reply 672-3. http://cid.oxfordjournals.org/content/36/5/671.long (Full article)

 

Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

To estimate the prevalence of viruses associated with chronic fatigue syndrome (CFS) and to control for genetic and environmental factors, we conducted a co-twin control study of 22 monozygotic twin pairs, of which one twin met criteria for CFS and the other twin was healthy. Levels of antibodies to human herpesvirus (HHV)-8, cytomegalovirus, herpes simplex virus 1 and 2, and hepatitis C virus were measured. Polymerase chain reaction (PCR) assays for viral DNA were performed on peripheral blood mononuclear cell specimens to detect infection with HHV-6, HHV-7, HHV-8, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, varicella zoster virus, JC virus, BK virus, and parvovirus B19. To detect lytic infection, plasma was tested by PCR for HHV-6, HHV-8, cytomegalovirus, and Epstein-Barr virus DNA, and saliva was examined for HHV-8 DNA. For all assays, results did not differ between the group of twins with CFS and the healthy twins.

Comment in: Diverse etiologies for chronic fatigue syndrome. [Clin Infect Dis. 2003]

 

Source: Koelle DM, Barcy S, Huang ML, Ashley RL, Corey L, Zeh J, Ashton S, Buchwald D. Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome. Clin Infect Dis. 2002 Sep 1;35(5):518-25. Epub 2002 Jul 31. http://cid.oxfordjournals.org/content/35/5/518.long (Full article)