Tag: herpes simplex

Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID

Abstract:

Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions.

Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS.

Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.

Source: Zheng Liu, Claudia Hollmann, Sharada Kalanidhi, Arnhild Grothey, Samuel Keating, Irene Mena-Palomo, Stephanie Lamer, Andreas Schlosser, Agnes Kaiping, Carsten Scheller, Franziska Sotzny, Anna Horn, Carolin Nuernberger, Vladimir Cejka, Boshra Afshar, Thomas Bahmer, Stefan Schreiber, Joerg Janne Vehreschild, Olga Milljukov, Christian Schaefer, Luzie Kretzler, Thomas Keil, Jens-Peter Reese, Felizitas A Eichner, Lena Schmidbauer, Peter U Heuschmann, Stefan Stoerk, Caroline Morbach, Gabriela Riemekasten, Niklas Beyersdorf, Carmen Scheibenbogen, Robert K Naviaux, Marshall Williams, Maria E Ariza, Bhupesh Kumar Prusty. Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID. medRxiv 2023.06.23.23291827; doi: https://doi.org/10.1101/2023.06.23.23291827 https://www.medrxiv.org/content/10.1101/2023.06.23.23291827v1 (Full text available as PDF file)

Gastric herpes simplex virus type 1 infection is associated with functional gastrointestinal disorders in the presence and absence of comorbid fibromyalgia: a pilot case-control study

Abstract:

Purpose: Animal studies have linked gastric herpesvirus infections to symptoms associated with functional gastrointestinal disorders (FGIDs). Herpesviruses have also been hypothesized to contribute to fibromyalgia (FM), a chronic pain syndrome frequently comorbid with FGIDs. The purpose of this study was to compare the prevalence of gastric herpesvirus infection in patients with FGIDs, with and without comorbid FM, to that of controls.

Methods: For this pilot case-control study, we enrolled 30 patients who met both the Rome IV diagnostic criteria for one or more FGIDs and the American College of Rheumatology 2010 criteria for FM, 15 patients with one or more FGIDs without comorbid FM, and 15 control patients. Following endoscopic examination, gastric biopsies were analyzed for herpesvirus DNA and protein, Helicobacter pylori infection, and histological evidence of gastritis. Importantly, the viral nonstructural protein ICP8 was used as a marker to differentiate cell-associated actively replicating virus from latent infection and/or free virus passing through the GI tract.

Results: Gastric herpes simplex virus type 1 (HSV-1) infection, as indicated by ICP8 presence, was significantly associated with FGIDs in the presence (OR 70.00, 95% CI 7.42-660.50; P < .001) and absence (OR 38.50, 95% CI 3.75-395.40; P < .001) of comorbid FM. Neither histological gastritis nor H. pylori infection were found to be associated with FGIDs or FM.

Conclusions: HSV-1 infection was identified in gastric mucosal biopsies from patients with diverse FGIDs, with and without comorbid FM. Larger, multi-center studies investigating the prevalence of this association are warranted.

Source: Duffy C, Pridgen WL, Whitley RJ. Gastric herpes simplex virus type 1 infection is associated with functional gastrointestinal disorders in the presence and absence of comorbid fibromyalgia: a pilot case-control study. Infection. 2022 Apr 21. doi: 10.1007/s15010-022-01823-w. Epub ahead of print. PMID: 35445970.  https://link.springer.com/article/10.1007/s15010-022-01823-w (Full text)

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

 

Human herpesvirus 6 and chronic fatigue syndrome

Abstract:

The cause of chronic fatigue syndrome (CFS) is still enigmatic. Using indirect immunofluorescence testing for measuring antibody against human herpesvirus 6 (HHV-6), this study investigated the association of CFS with infection by HHV-6. Seventeen patients (group A) fulfilling the Centers for Disease Control (CDC) definition for CFS were compared with eight patients (group B) with chronic fatigue but not meeting the CDC criteria.

No significant difference was found between the two groups for 30 parameters including sex, age, exposure to children and serology for Epstein-Barr virus, cytomegalovirus, herpes simplex virus, and toxoplasma. Univariate analysis showed that patients in group A complained more frequently of a sore throat, headache and of recurrent type of fatigue.

These three parameters are discriminant in identifying patients who will meet the CDC case definition of CFS. The titre of antibody against HHV-6 in group A (1:99) was significantly higher than in group B (1:15) (P=0.007). Elevated HHV-6 titres suggests that this virus could be a cofactor in the pathogenesis of CFS.

 

Source: Eymard D, Lebel F, Miller M, Turgeon F. Human herpesvirus 6 and chronic fatigue syndrome. Can J Infect Dis. 1993 Jul;4(4):199-202. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250792/  (Full article)

 

A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause?

Abstract:

A cluster of 134 patients who had undergone Epstein-Barr virus (EBV) serological testing because of suspected chronic EBV syndrome was investigated in Nevada.

Fifteen case-patients were identified who had severe, persistent fatigue of undetermined etiology for more than two months. When compared with the remaining 119 patients who had less severe illnesses and with 30 age-, sex-, and race-matched control-persons, these 15 patients had significantly higher antibody titers against various components of EBV and against cytomegalovirus and herpes simplex and measles viruses. Epstein-Barr virus serology could not reliably differentiate individual case-patients from the others, and the reproducibility of the tests within and among laboratories was poor.

As a group, the case-patients appear to have had a syndrome that is characterized by chronic fatigue, fever, sore throat, and lymphadenopathy. The relationship of this fatigue syndrome to EBV is unclear; further studies are needed to determine its etiology.

 

Source: Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, Schonberger LB. A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? JAMA. 1987 May 1;257(17):2297-302. http://www.ncbi.nlm.nih.gov/pubmed/3033337