The Influence of Virus Infection on Microglia and Accelerated Brain Aging

Filgueira, Luis; Larionov, Alexey; Lannes, Nils

doi:10.3390/cells10071836

Cited by 38 publications

(21 citation statements)

References 246 publications

(314 reference statements)

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“…As cell-cell fusion is a major trigger of cellular senescence, viruses may have developed the ability to exploit host fusogens, promoting premature aging ( Gal et al., 2019 ). Indeed, epidemiological and research data have associated neurotropic viruses with accelerated brain aging and neurodegenerative disorders ( Mavrikaki et al., 2021 ; Sait et al., 2021 ; Filgueira et al., 2021 ; Dowd and McKernan, 2021 ). Along these lines, herpes simplex virus 1 (HSV-1) and human herpesvirus 6 (HHV-6) have been associated with Alzheimer’s disease (AD) and multiple sclerosis (MS) respectively, while human immunodeficiency virus type 1 (HIV-1) contributes to HIV-associated neurocognitive disorders (HAND, 18-19).…”

Section: Introductionmentioning

confidence: 99%

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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A growing body of epidemiological and research data has associated neurotropic viruses with accelerated brain aging and increased risk of neurodegenerative disorders. Many viruses replicate optimally in senescent cells, as they offer a hospitable microenvironment with persistently elevated cytosolic calcium, abundant intracellular iron, and low interferon type I. As cell-cell fusion is a major driver of cellular senescence, many viruses have developed the ability to promote this phenotype by forming syncytia. Cell-cell fusion is associated with immunosuppression mediated by phosphatidylserine externalization that enable viruses to evade host defenses. In hosts, virus-induced immune dysfunction and premature cellular senescence may predispose to neurodegenerative disorders. This concept is supported by novel studies that found postinfectious cognitive dysfunction in several viral illnesses, including human immunodeficiency virus-1, herpes simplex virus-1, and SARS-CoV-2. Virus-induced pathological syncytia may provide a unified framework for conceptualizing neuronal cell cycle reentry, aneuploidy, somatic mosaicism, viral spreading of pathological Tau and elimination of viable synapses and neurons by neurotoxic astrocytes and microglia. In this narrative review, we take a closer look at cell-cell fusion and vesicular merger in the pathogenesis of neurodegenerative disorders. We present a “decentralized” information processing model that conceptualizes neurodegeneration as a systemic illness, triggered by cytoskeletal pathology. We also discuss strategies for reversing cell-cell fusion, including, TMEM16F inhibitors, calcium channel blockers, senolytics, and tubulin stabilizing agents. Finally, going beyond neurodegeneration, we examine the potential benefit of harnessing fusion as a therapeutic strategy in regenerative medicine.

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Section: Introductionmentioning

confidence: 99%

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Altered microbiota composition has also been associated with the development of NDs, therefore microbiome-microglia interactions might influence NDs pathogenesis ( 68 ). Viruses which are also associated with the development of NDs and can also interfere with microglia functions ( 91 ). Therefore, since alternation in microbiota can influence microglia immune responses against viral infection, microbiota-virus-microglia interactions could also influence the pathogenesis of NDs.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effects of microbiota-derived metabolites at the crossroad of neurodegenerative diseases and viral infection: network-based bioinformatics insights

Onisiforou

Spyrou

2022

Front. Immunol.

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Bidirectional cross-talk between commensal microbiota and the immune system is essential for the regulation of immune responses and the formation of immunological memory. Perturbations of microbiome-immune system interactions can lead to dysregulated immune responses against invading pathogens and/or to the loss of self-tolerance, leading to systemic inflammation and genesis of several immune-mediated pathologies, including neurodegeneration. In this paper, we first investigated the contribution of the immunomodulatory effects of microbiota (bacteria and fungi) in shaping immune responses and influencing the formation of immunological memory cells using a network-based bioinformatics approach. In addition, we investigated the possible role of microbiota-host-immune system interactions and of microbiota-virus interactions in a group of neurodegenerative diseases (NDs): Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our analysis highlighted various aspects of the innate and adaptive immune response systems that can be modulated by microbiota, including the activation and maturation of microglia which are implicated in the development of NDs. It also led to the identification of specific microbiota components which might be able to influence immune system processes (ISPs) involved in the pathogenesis of NDs. In addition, it indicated that the impact of microbiota-derived metabolites in influencing disease-associated ISPs, is higher in MS disease, than in AD, PD and ALS suggesting a more important role of microbiota mediated-immune effects in MS.

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“…The enrichment studies observed an increased population of myeloid cells (in the pancreas, intestine, kidney, lung, liver) and microglia (in the brain), which form part of the innate immune response against the virus. These cell types have a known role in phagocytosis and anti-inflammation, biochemical pathways commonly observed in response to viral infection [119, 120]. Antigen-presenting cells (A.P.C.)…”

Section: Discussionmentioning

confidence: 99%

In Silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions

Sen

Kaur

2022

Preprint

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COVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. The host response to SARS-CoV-2 infection is not clearly understood. Patients infected with SARS-CoV-2 exhibit heterogeneous intensity of symptoms, i.e., asymptomatic, mild, and severe. Moreover, effects on organs also vary from person to person. These heterogeneous responses pose pragmatic hurdles for implementing appropriate therapy and management of COVID-19 patients. Post-COVID complications pose another major challenge in managing the health of these patients. Thus, understanding the impact of disease severity at the molecular level is vital to delineate the precise host response and management. In the current study, we performed a comprehensive transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients. Exploratory data analysis using Principal Component Analysis (PCA) showed the distinct clusters of asymptomatic and severe patients. Subsequently, the differential gene expression analysis using DESeq2 identified 1,224 significantly upregulated genes (logFC>= 1.5, p-adjusted value <0.05) and 268 significantly downregulated genes (logFC<= -1.5, p-adjusted value <0.05) in severe samples in comparison to asymptomatic samples. Eventually, Gene Set Enrichment Analysis (GSEA) of upregulated genes revealed significant enrichment of terms, i.e., anti-viral and anti-inflammatory pathways, secondary infections, Iron homeostasis, anemia, cardiac-related, etc. Gene set enrichment analysis of downregulated genes indicates lipid metabolism, adaptive immune response, translation, recurrent respiratory infections, heme-biosynthetic pathways, etc. In summary, severe COVID-19 patients are more susceptible to other health issues/concerns, non-viral pathogenic infections, atherosclerosis, autoinflammatory diseases, anemia, male infertility, etc. And eventually, these findings provide insight into the precise therapeutic management of severe COVID-19 patients and efficient disease management.

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The Influence of Virus Infection on Microglia and Accelerated Brain Aging

Cited by 38 publications

References 246 publications

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Immunomodulatory effects of microbiota-derived metabolites at the crossroad of neurodegenerative diseases and viral infection: network-based bioinformatics insights

In Silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions

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