Interaction of HERVs with PAMPs in Dysregulation of Immune Response Cascade Upon SARS-CoV-2 Infections DOI Open Access
Marijana Turčić, Sandra Kraljević Pavelić, Dragan Trivanović

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13360 - 13360

Published: Dec. 12, 2024

Human endogenous retroviruses (HERVs) are genomic fragments integrated into human DNA from germline infections by exogenous that threatened primates early in their evolution and inherited vertically the germline. So far, HERVs have been studied context of extensive immunopathogenic, neuropathogenic even oncogenic effects within host. In particular, our paper, we elaborate on aspects related to possible correlation transposable HERV elements’ activation SARS-CoV-2 spike protein’s presence cells COVID-19 patients or upon vaccination with implications for natural adaptive immunity. release cytokines TNF-α, IL-1β IL-6 occurs such cases plays a notable role sustaining chronic inflammation. Moreover, well-known interindividual variations might partially account interpersonal variability symptoms unwanted events post-vaccination. Accordingly, further studies required clarify triggering HERVs.

Language: Английский

Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infection DOI Creative Commons
Xuefei Guo, Yang Zhao, Fuping You

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 5, 2024

Endogenous retroviruses (ERVs) derived from the long terminal repeat (LTR) family of transposons constitute a significant portion mammalian genome, with origins tracing back to ancient viral infections. Despite comprising approximately 8% human specific role ERVs in pathogenesis COVID-19 remains unclear. In this study, we conducted genome-wide identification peripheral blood mononuclear cells (hPBMCs) and primary lung epithelial monkeys mice, both infected uninfected SARS-CoV-2. We identified 405, 283, 206 significantly up-regulated transposable elements (TEs) hPBMCs, monkeys, respectively. This included 254, 119, 68, 28 found hPBMCs severe mild patients, transgenic mice expressing ACE2 receptor (hACE2) Furthermore, analysis using Genomic Regions Enrichment Annotations Tool (GREAT) revealed certain parental genomic sequences these patients may be involved various biological processes, including histone modification replication. Of particular interest, 210 specifically group. The genes associated differentially expressed were enriched processes such as immune response activation modification. HERV1_I-int: ERV1:LTR LTR7Y: highlighted potential biomarkers for evaluating severity COVID-19. Additionally, validation our findings RT-qPCR Bone Marrow-Derived Macrophages (BMDMs) by HSV-1 VSV provided further support results. study offers insights into expression patterns roles following infection, providing valuable resource future studies on their interaction

Language: Английский

Citations

6
Blood Biomarkers of Long COVID: A Systematic Review DOI
Callum Thomas, Mark A. Faghy, Corinna Chidley

et al.

Molecular Diagnosis & Therapy, Journal Year: 2024, Volume and Issue: 28(5), P. 537 - 574

Published: Aug. 5, 2024

Language: Английский

Citations

6
An unexpected IgE anti-receptor binding domain response following natural infection and different types of SARS-CoV-2 vaccines DOI Creative Commons
Amanda Izeli Portilho, Valéria Oliveira Silva, Hernan Hermes Monteiro da Costa

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 28, 2024

Humoral response to SARS-CoV-2 has been studied, predominantly the classical IgG and its subclasses. Although IgE antibodies are typically specific allergens or parasites, a few reports describe their production in other viruses. Here, we investigated receptor binding domain (RBD) of Brazilian cohort following natural infection vaccination. Samples from 59 volunteers were assessed after (COVID-19), primary immunization with vectored (ChAdOx1) inactivated (CoronaVac) vaccines, booster mRNA (BNT162b2) vaccine. Natural COVID-19 induced IgE, but vaccination increased levels. Subjects vaccinated two doses ChAdOx1 exhibited more robust than those immunized CoronaVac; however, boosting BNT162b2, all groups presented similar showed intermediate-to-high avidity, especially We also found IgG4 antibodies, mainly booster, they moderately correlated IgE. ELISA results confirmed by control assays, using depletion protein G lack reactivity heterologous antigen. In our cohort, no clinical data could be associated response. advocate for further research on role viral immunity, extending beyond allergies parasitic infections.

Language: Английский

Citations

5
Patients with psychosis spectrum disorders hospitalized during the COVID-19 pandemic unravel overlooked SARS-CoV-2 past infection clustering with HERV-W ENV expression and chronic inflammation DOI Creative Commons
Ryad Tamouza, Urs Meyer, Alexandre Lucas

et al.

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: July 31, 2023

Abstract Epidemiology has repeatedly associated certain infections with a risk of further developing psychiatric diseases. Such can activate retro-transposable genetic elements (HERV) known to trigger immune receptors and impair synaptic plasticity neuroreceptors. Since the HERV-W ENV protein was recently shown co-cluster pro-inflammatory cytokines in subgroup patients schizophrenia or bipolar disorder, we questioned influence COVID-19 pandemic on psychosis spectrum disorders (PSD). Present results revealed that (i) SARS-CoV-2 serology shows high prevalence titers antibodies PSD, (ii) is detected seropositive individuals only (iii) positivity co-clustered serum levels psychotic patients. These thus suggest infection many now admitted psychiatry department did not cause severe COVID-19. They also confirm previously reported association elevated In context pandemic, this cluster found PSD cases, suggesting dominant virus cytokine expression, and/or patients’ greater susceptibility infection. Further investigation an interplay between viral clinical evolution such needed. However, defined phenotype HERV expression calls for differential therapeutic approach psychoses, therefore precision medicine development.

Language: Английский

Citations

12
Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses DOI Creative Commons

Eirini Apostolou,

Anders Rosén

Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 296(1), P. 93 - 115

Published: May 1, 2024

Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease presenting with severe fatigue, post‐exertional malaise, and cognitive disturbances—among spectrum of symptoms—that collectively render the patient housebound or bedbound. Epigenetic studies in ME/CFS confirm alterations and/or malfunctions cellular organismal physiology associated immune responses, metabolism, cell death proliferation, neuronal endothelial function. The sudden onset follows major stress factor that, approximately 70% cases, involves viral infection, symptoms overlap those long COVID. Viruses primarily linked to pathology are symbiotic herpesviruses, which follow bivalent latent–lytic lifecycle. complex interaction between viruses hosts strategies from both sides: evasion persistence by viruses, activation clearance host. This dynamic imperative for herpesviruses that facilitate their through epigenetic regulation own host genome. In current article, we provide an overview signatures demonstrated focus on potential latent viruses—particularly Epstein–Barr virus—may employ long‐term reprograming ME/CFS. could aid elucidating relevant biological pathways impacted reflect physiological variations among patients stem environmental triggers, including exogenous altered activity.

Language: Английский

Citations

4
Cognitive Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Aetiology and Potential Treatments DOI Open Access
Amolak S. Bansal, Katharine A. Seton, J.C. Brooks

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1896 - 1896

Published: Feb. 22, 2025

Systemic infection and inflammation impair mental function through a combination of altered attention cognition. Here, we comprehensively review the relevant literature report personal clinical observations to discuss relationship between infection, peripheral inflammation, cerebral cognitive dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Cognitive ME/CFS could result from low-grade persistent associated raised pro-inflammatory cytokines. This may be caused by both infectious non-infectious stimuli lead regional blood flow accompanied disturbed neuronal function. Immune dysregulation that manifests as subtle immunodeficiency or autoimmunity targeting one more receptors also contributing factor. Efforts reduce systemic viral reactivation improve mitochondrial energy generation have potential this highly disabling condition.

Language: Английский

Citations

0
Anti‐SARS‐CoV‐2 Antibodies in Long‐COVID—Markers of Protection or Elevated Risk? A Systematic Review DOI Open Access
Sylvia Mink,

F.X. Wilhelm,

Janne Cadamuro

et al.

Reviews in Medical Virology, Journal Year: 2025, Volume and Issue: 35(2)

Published: Feb. 24, 2025

Long-COVID affects a significant number of COVID-19 survivors, profoundly impacting daily life and work. Although research suggests potential link between antibody levels long-COVID risk, findings remain inconclusive. Understanding dynamics could support the identification patients at improve diagnosis, guide protective strategies such as vaccination. Despite growing evidence, no systematic review has yet evaluated current literature on this topic. We therefore aimed to synthesise evaluate existing evidence association anti-SARS-CoV-2 titres long-COVID, with goal clarifying their role in predicting guiding patient management, informing future directions. Studies published PubMed/Medline databases January 2020 October 2024 were included without language restrictions. body fluids other than serum/blood excluded. Study selection quality assessment was conducted independently by two researchers. After screening 949 studies, 58 studies encompassing 53,739 individuals, 7812 patients, included. Evidence highly heterogenous but most reported an anti-SARS-CoV-2-spike antibodies although nature appeared be dependent time from acute infection. Low during associated increased risk long-COVID. The low that maintaining sufficiently high may protective. However, level is further sufficient power are required confirm potentially determine cutoffs.

Language: Английский

Citations

0
HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity DOI Open Access
Karen Giménez-Orenga,

Eva Martín‐Martínez,

Lubov Nathanson

et al.

Published: Feb. 5, 2025

Research of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), two acquired chronic illnesses affecting mainly females, has failed to ascertain their frequent co-appearance etiology. Despite prior detection human endogenous retrovirus (HERV) activation in these diseases, the potential biomarker value HERV expression profiles for diagnosis, relationship with patient immune systems symptoms had remained unexplored. By using HERV-V3 high-density microarrays (including over 350k elements more than 1500 immune-related genes) interrogate transcriptomes peripheral blood mononuclear cells from female patients diagnosed ME/CFS, FM or both, matched healthy controls (n=43), this study fills gap knowledge. Hierarchical clustering strikingly allowed perfect participant assignment into four distinct groups: FM, co-diagnosed, healthy, pointing at a potent differentiate between hard-to-diagnose syndromes. Differentially expressed HERV-immune-gene modules revealed unique each groups highlighting decreased γδ T cells, increased plasma resting CD4 memory correlating symptom severity ME/CFS. Moreover, sequences coincided enrichment binding targeted by transcription factors which recruit SETDB1 TRIM28, known epigenetic silencers HERV, offering mechanistic explanation findings. Unexpectedly, appeared minimally affected co-diagnosed denoting new nosological entity low impact, seemingly relevant aspect diagnosis treatment prevalent group patients.

Language: Английский

Citations

0
HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity DOI Open Access
Karen Giménez-Orenga,

Eva Martín‐Martínez,

Lubov Nathanson

et al.

Published: Feb. 5, 2025

Research of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), two acquired chronic illnesses affecting mainly females, has failed to ascertain their frequent co-appearance etiology. Despite prior detection human endogenous retrovirus (HERV) activation in these diseases, the potential biomarker value HERV expression profiles for diagnosis, relationship with patient immune systems symptoms had remained unexplored. By using HERV-V3 high-density microarrays (including over 350k elements more than 1500 immune-related genes) interrogate transcriptomes peripheral blood mononuclear cells from female patients diagnosed ME/CFS, FM or both, matched healthy controls (n=43), this study fills gap knowledge. Hierarchical clustering strikingly allowed perfect participant assignment into four distinct groups: FM, co-diagnosed, healthy, pointing at a potent differentiate between hard-to-diagnose syndromes. Differentially expressed HERV-immune-gene modules revealed unique each groups highlighting decreased γδ T cells, increased plasma resting CD4 memory correlating symptom severity ME/CFS. Moreover, sequences coincided enrichment binding targeted by transcription factors which recruit SETDB1 TRIM28, known epigenetic silencers HERV, offering mechanistic explanation findings. Unexpectedly, appeared minimally affected co-diagnosed denoting new nosological entity low impact, seemingly relevant aspect diagnosis treatment prevalent group patients.

Language: Английский

Citations

0
Recapitulation and reversal of neuropsychiatric phenotypes in a mouse model of human endogenous retrovirus type W expression DOI Creative Commons
Felisa Herrero, Celine Heeb,

Michelle G. Meier

et al.

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Human endogenous retroviruses (HERVs) are inherited genetic elements derived from exogenous retroviral infections occurring throughout evolution. Accumulating evidence implicates increased expression of HERV type W envelope (HERV-W ENV) in psychiatric and neurodevelopmental disorders. To gain more mechanistic insights into the neurobiological disease pathways affected by HERV-W ENV expression, we took advantage a mouse model that recapitulates human-specific protein. Behavioral cognitive phenotyping transgenic (TG) mice expressing wild-type (WT) controls showed this caused deficits numerous functional domains, including repetitive behavior, social object recognition memory, sensorimotor gating. Genome-wide RNA sequencing hippocampal tissue demonstrated led to transcriptomic alterations highly relevant for disorders, functions, synaptic development. Differential gene TG encompassed downregulation several genes associated with schizophrenia autism spectrum disorder, Setd1a , Cacna1g Ank3 Shank3 as well histone methyltransferase belong Set1-like H3 lysine 4 (H3K4) family ( Kmt2a Kmt2b Kmt2d ). Concomitant latter, displayed enzymatic activity lysine-specific demethylase-1 (LSD1), H3K4 mono-methylation, decreased di- tri-methylation hippocampus. Importantly, pharmacological inhibition LSD1 through oral ORY-1001 treatment normalized abnormal methylation rescued behavioral mice. In conclusion, our study suggests has capacity disrupt various functions alter brain transcriptome manner is Moreover, identified epigenetic may offer avenues interventions against induced HERW-W expression.

Language: Английский

Citations

0