Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Schreiner, Philipp; Harrer, Thomas; Scheibenbogen, Carmen; Lamer, Stephanie; Schlösser, Andreas; Naviaux, Robert K.; Prusty, Bhupesh K.

doi:10.4049/immunohorizons.2000006

Cited by 45 publications

(52 citation statements)

References 56 publications

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“…Additionally, Schreiner et al. showed that in patients with myalgic encephalomyelitis/chronic fatigue syndrome, mitochondria were strongly fragmented by human herpesvirus 6 (HHV-6) and HHV-7; this is believed to be the trigger of the disease ( 58 ). Whether such fragmentation of mitochondria that results in the production of mitochondrial antibody occurs with SARS-CoV-2 certainly deserves future investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Holder and Reddy (57) showed how interaction between SARS-CoV-2 and immune cells alters mitochondrial activities in host cells, providing a receptive intracellular environment for viral replication in infected cells that may contribute to the progression of the disease in COVID-19 patients (57). Additionally, Schreiner et al showed that in patients with myalgic encephalomyelitis/chronic fatigue syndrome, mitochondria were strongly fragmented by human herpesvirus 6 (HHV-6) and HHV-7; this is believed to be the trigger of the disease (58). Whether such fragmentation of mitochondria that results in the production of mitochondrial antibody occurs with SARS-CoV-2 certainly deserves future investigation.…”

Section: Discussionmentioning

confidence: 99%

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Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

Vojdani²,

2021

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We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

Vojdani²,

2021

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“…Other reports have identified a deficit in Complex V (ATP synthase) activity of the electron transport chain (ETC) in lymphocytes, with a compensatory up-regulation of respiratory capacity ( 96 , 97 ), and a decrease in mitochondrial membrane potential in CD8+ T cells ( 98 ). Serum from ME/CFS patients reportedly contains a factor that induces mitochondrial fragmentation ( 99 ).…”

Section: Impaired Energy Metabolism In Covid-19 and Me/cfsmentioning

confidence: 99%

Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome

Paul

Lemle

Komaroff

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

179

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Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called “long COVID-19,” reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.

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“…Short-term changes in mitochondrial function that are reversible can lead to long-term benefits over a lifetime. For example, in the context of microbial infection, reduction in mitochondrial bioenergetic capacity is part of the natural antiviral response [81].…”

Section: Discussionmentioning

confidence: 99%

Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder

et al. 2021

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Since 2012, studies in mice, rats, and humans have suggested that abnormalities in purinergic signaling may be a final common pathway for many genetic and environmental causes of autism spectrum disorder (ASD). The current study in mice was conducted to characterize the bioenergetic, metabolomic, breathomic, and behavioral features of acute hyperpurinergia triggered by systemic injection of the purinergic agonist and danger signal, extracellular ATP (eATP). Responses were studied in C57BL/6J mice in the maternal immune activation (MIA) model and controls. Basal metabolic rates and locomotor activity were measured in CLAMS cages. Plasma metabolomics measured 401 metabolites. Breathomics measured 98 volatile organic compounds. Intraperitoneal eATP dropped basal metabolic rate measured by whole body oxygen consumption by 74% ± 6% (mean ± SEM) and rectal temperature by 6.2˚ ± 0.3˚C in 30 minutes. Over 200 metabolites from 37 different biochemical pathways where changed. Breathomics showed an increase in exhaled carbon monoxide, dimethylsulfide, and isoprene. Metabolomics revealed an acute increase in lactate, citrate, purines, urea, dopamine, eicosanoids, microbiome metabolites, oxidized glutathione, thiamine, niacinamide, and pyridoxic acid, and decreased folate-methylation-1-carbon intermediates, amino acids, short and medium chain acyl-carnitines, phospholipids, ceramides, sphingomyelins, cholesterol, bile acids, and vitamin D similar to some children with ASD. MIA animals were hypersensitive to postnatal exposure to eATP or poly(IC), which produced a rebound increase in body temperature that lasted several weeks before returning to baseline. Acute hyperpurinergia produced metabolic and behavioral changes in mice. The behaviors and metabolic changes produced by ATP injection were associated with mitochondrial functional changes that were profound but reversible.

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Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Cited by 45 publications

References 56 publications

Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome

Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder

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