Epstein-Barr Virus-Induced Genes and Endogenous Retroviruses in Immortalized B Cells from Patients with Multiple Sclerosis

Wieland, Lisa; Schwarz, Tommy; Engel, Kristina; Volkmer, Ines; Krüger, Anna; Tarabuko, Alexander; Junghans, Jutta; Kornhuber, Malte; Hoffmann, F.; Staege, Martin S.; Emmer, Alexander

doi:10.3390/cells11223619

Cited by 15 publications

(7 citation statements)

References 75 publications

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“…The scenario is reminiscent of a chain-reaction, where one virus triggers a second virus, as exemplified by SARS-CoV-2 triggering EBV ( 10 ), and human endogenous retroviruses (HERVs). Activation of HERV by EBV might be the missing link between an initial EBV infection and the later onset of multiple sclerosis (MS) ( 15 ). There are considerable phenotypic and neuroimmune elements overlapping in ME/CFS and MS, including anti-EBNA1 IgG elevation ( 10 , 16 – 18 ).…”

Section: Discussionmentioning

confidence: 99%

Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa

et al. 2023

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The post-viral fatigue syndromes long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have multiple, potentially overlapping, pathological processes. These include persisting reservoirs of virus, e.g., SARS-CoV-2 in long COVID patient’s tissues, immune dysregulation with or without reactivation of underlying pathogens, such as Epstein–Barr virus (EBV) and human herpesvirus 6 (HHV6), as we recently described in ME/CFS, and possibly yet unidentified viruses. In the present study we tested saliva samples from two cohorts for IgG against human adenovirus (HAdV): patients with ME/CFS (n = 84) and healthy controls (n = 94), with either mild/asymptomatic SARS-CoV-2 infection or no infection. A significantly elevated anti-HAdV IgG response after SARS-CoV-2 infection was detected exclusively in the patient cohort. Longitudinal/time analysis, before and after COVID-19, in the very same individuals confirmed HAdV IgG elevation after. In plasma there was no HAdV IgG elevation. We conclude that COVID-19 triggered reactivation of dormant HAdV in the oral mucosa of chronic fatigue patients indicating an exhausted dysfunctional antiviral immune response in ME/CFS, allowing reactivation of adenovirus upon stress encounter such as COVID-19. These novel findings should be considered in clinical practice for identification of patients that may benefit from therapy that targets HAdV as well.

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Section: Discussionmentioning

confidence: 99%

Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa

et al. 2023

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“…HERV-K Gag is also activated in EBV-triggered immortalized cells from patients with multiple sclerosis (MS) ( Wieland et al., 2022 ). Regarding HERV-W, which is strongly associated with MS pathogenesis, there is evidence of HERV-W gp350 transactivation by EBV infection in peripheral blood mononuclear cells (PBMC) from MS patients ( Mameli et al., 2012 ).…”

Section: Exogenous Viruses and Hervsmentioning

confidence: 99%

Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology

da Silva,

Guedes,

Santos

et al. 2024

Front. Cell. Infect. Microbiol.

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The notion that viruses played a crucial role in the evolution of life is not a new concept. However, more recent insights suggest that this perception might be even more expansive, highlighting the ongoing impact of viruses on host evolution. Endogenous retroviruses (ERVs) are considered genomic remnants of ancient viral infections acquired throughout vertebrate evolution. Their exogenous counterparts once infected the host’s germline cells, eventually leading to the permanent endogenization of their respective proviruses. The success of ERV colonization is evident so that it constitutes 8% of the human genome. Emerging genomic studies indicate that endogenous retroviruses are not merely remnants of past infections but rather play a corollary role, despite not fully understood, in host genetic regulation. This review presents some evidence supporting the crucial role of endogenous retroviruses in regulating host genetics. We explore the involvement of human ERVs (HERVs) in key physiological processes, from their precise and orchestrated activities during cellular differentiation and pluripotency to their contributions to aging and cellular senescence. Additionally, we discuss the costs associated with hosting a substantial amount of preserved viral genetic material.

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“…RNAseq data was generated from 1 µg RNA by Novogene (Cambridge, UK) using the Illumina Novaseq6000 system. A further data procedure was conducted, essentially as described [37], using the Galaxy server (https://usegalaxy.eu/ (accessed on 24 November 2022)). Reads were mapped against the human reference genome HG38 using HISAT2, and quantification was performed using htseq-count.…”

Section: Rnaseq Analysismentioning

confidence: 99%

Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells

Schildhauer,

Selke,

Staege

et al. 2023

Cells

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Glioblastoma (GBM) is a highly aggressive brain tumor that often utilizes aerobic glycolysis for energy production (Warburg effect), resulting in increased methylglyoxal (MGO) production. MGO, a reactive dicarbonyl compound, causes protein alterations and cellular dysfunction via glycation. In this study, we investigated the effect of glycation on sialylation, a common post-translational modification implicated in cancer. Our experiments using glioma cell lines, human astrocytes (hA), and primary glioma samples revealed different gene expressions of sialyltransferases among cells, highlighting the complexity of the system. Glycation has a differential effect on sialyltransferase expression, upregulating ST8SIA4 in the LN229 and U251 cell lines and decreasing the expression in normal hA. Subsequently, polysialylation increased in the LN229 and U251 cell lines and decreased in hA. This increase in polysialylation could lead to a more aggressive phenotype due to its involvement in cancer hallmark processes such as immune evasion, resistance to apoptosis, and enhancing invasion. Our findings provide insights into the mechanisms underlying GBM aggressiveness and suggest that targeting glycation and sialylation could be a potential therapeutic strategy.

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Epstein-Barr Virus-Induced Genes and Endogenous Retroviruses in Immortalized B Cells from Patients with Multiple Sclerosis

Cited by 15 publications

References 75 publications

Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa

Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa

Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology

Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells

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