WHSC1L1-mediated epigenetic downregulation of VMP1 participates in herpes simplex virus 1 infection-induced mitophagy impairment and neuroinflammation

Yao, Yan; Gu, Juxian; Li, Meng; Li, Guoce; Ai, Jingyi; Zhao, Li

doi:10.1016/j.molimm.2023.09.012

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…Additionally, Herpes Simplex Virus Type 1 infection triggers microglial activation and neuroinflammation through the downregulation of VMP1 and upregulation of WHSC1L1, a shift that impairs mitophagy and amplifies neuroinflammation. This process is mediated by the epigenetic modification of VMP1, where WHSC1L1-induced H3K36me2 recruits DNMT3A, a DNA methylation enzyme, to repress VMP1 transcription, potentially involving methylation modifications of the VMP1 RNA ( Yao et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology

Tong,

Wang,

Gao

et al. 2024

Front. Cell Dev. Biol.

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Vacuole membrane protein 1 (VMP1) is an integral membrane protein that plays a pivotal role in cellular processes, particularly in the regulation of autophagy. Autophagy, a self-degradative mechanism, is essential for maintaining cellular homeostasis by degradation and recycling damaged organelles and proteins. VMP1 involved in the autophagic processes include the formation of autophagosomes and the subsequent fusion with lysosomes. Moreover, VMP1 modulates endoplasmic reticulum (ER) calcium levels, which is significant for various cellular functions, including protein folding and cellular signaling. Recent studies have also linked VMP1 to the cellular response against viral infections and lipid droplet (LD). Dysregulation of VMP1 has been observed in several pathological conditions, including neurodegenerative diseases such as Parkinson’s disease (PD), pancreatitis, hepatitis, and tumorogenesis, underscoring its potential as a therapeutic target. This review aims to provide an overview of VMP1’s multifaceted roles and its implications in disease pathology.

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Section: Introductionmentioning

confidence: 99%

VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology

Tong,

Wang,

Gao

et al. 2024

Front. Cell Dev. Biol.

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The scramblases VMP1 and TMEM41B are required for primitive endoderm specification by targeting WNT signaling

Holzner,

Sonicki,

Hunn

et al. 2024

Cell Death Differ

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The ER-resident proteins VMP1 and TMEM41B share a conserved DedA domain, which confers lipid scramblase activity. Loss of either gene results in embryonic lethality in mice and defects in autophagy and lipid droplet metabolism. To investigate their role in pluripotency and lineage specification, we generated Vmp1 and Tmem41b mutations in mouse embryonic stem cells (ESCs). We observed that ESCs carrying mutations in Vmp1 and Tmem41b show robust self-renewal and an unperturbed pluripotent expression profile but accumulate LC3-positive autophagosomes and lipid droplets consistent with defects in autophagy and lipid metabolism. ESCs carrying combined mutations in Vmp1 and Tmem41b can differentiate into a wide range of embryonic cell types. However, differentiation into primitive endoderm-like cells in culture is impaired, and the establishment of extra-embryonic endoderm stem (XEN) cells is delayed. Mechanistically, we show the deregulation of genes that are associated with WNT signaling. This is further confirmed by cell surface proteome profiling, which identified a significant reduction of the WNT-receptor FZD2 at the plasma membrane in Vmp1 and Tmem41b double mutant ESCs. Importantly, we show that transgenic expression of Fzd2 rescues XEN differentiation. Our findings identify the role of the lipid scramblases VMP1 and TMEM41B in WNT signaling during extra-embryonic endoderm development and characterize their distinct and overlapping functions.

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Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine

Park,

Shin,

Jeon

et al. 2024

Biomol Ther (Seoul)

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Viral infections are increasingly recognized as triggers for depressive disorders, particularly following the SARS-CoV-2 pandemic and the rise of long COVID. Viruses such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV) are linked to depression through complex neurobiological mechanisms. These include immune system dysregulation, chronic inflammation, and neurotransmitter imbalances that affect brain function and mood regulation. Viral activation of the immune system leads to the release of pro-inflammatory cytokines, resulting in neuroinflammation and associated depressive symptoms. Furthermore, specific viruses can disrupt neurotransmitter systems, including serotonin, dopamine, and glutamate, all of which are essential for mood stabilization. The unique interactions of different viruses with these systems underscore the need for virus-specific therapeutic approaches. Current broad-spectrum treatments often overlook the precise neurobiological pathways involved in post-viral depression, reducing their efficacy. This review emphasizes the need to understand these virus-specific interactions to create tailored interventions that directly address the neurobiological effects induced by each type of virus. These interventions may include immunomodulatory treatments that target persistent inflammation, antiviral therapies to reduce the viral load, or neuroprotective strategies that restore neurotransmitter balance. Precision medicine offers promising avenues for the effective management of virus-induced depression, providing patient-specific approaches that address the specific biological mechanisms involved. By focusing on the development of these targeted treatments, this review aims to pave the way for a new era in psychiatric care that fully addresses the root causes of depression induced by viral infections.

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WHSC1L1-mediated epigenetic downregulation of VMP1 participates in herpes simplex virus 1 infection-induced mitophagy impairment and neuroinflammation

Cited by 3 publications

References 36 publications

VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology

VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology

The scramblases VMP1 and TMEM41B are required for primitive endoderm specification by targeting WNT signaling

Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine

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