COVID-19 Infection as a Possible Trigger for POLG-Related Mitochondrial Disease: A Case Report

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

A six-year-old child presented with an acute onset of refractory epileptic seizures during a coronavirus disease 2019 (COVID-19) infection. As her clinical condition progressed, she developed super-refractory status epilepticus, resulting in significant cognitive and motor impairments. Genetic analysis revealed homozygous mutation the DNA Polymerase Gamma, Catalytic Subunit (POLG) gene (c.1399G>A; p.Ala467Thr), confirming diagnosis Alpers-Huttenlocher syndrome. The course was characterized by developmental regression, it ultimately culminated liver failure multiorgan dysfunction, death. This case underscores critical importance early genetic evaluation children unexplained seizures, particularly for detecting underlying mitochondrial disorders such as POLG-related syndromes. Mitochondrial function is highly sensitive to physiological environmental stressors, including viral infections. Pathogens hepatitis viruses, influenza virus, HIV, respiratory syncytial virus (RSV), severe syndrome 2 (SARS-CoV-2) can exacerbate dysfunction. Therefore, identifying vulnerabilities these patients essential optimizing management strategies potentially mitigating rapid decline.

Language: Английский

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HTLV-1 Tax induces PINK1-Parkin-dependent mitophagy to mitigate activation of the cGAS-STING pathway

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Abstract Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult leukemia/lymphoma (ATLL) and neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax regulatory protein plays a critical role in persistence pathogenesis; however, underlying mechanisms are poorly understood. Here we show that dynamically regulates mitochondrial reactive oxygen species (ROS) membrane potential to trigger dysfunction. recruited damaged mitochondria through its interaction with IKK subunit NEMO directly engages ubiquitin-dependent PINK1-Parkin pathway induce mitophagy. also recruits autophagy receptors NDP52 p62/SQSTM1 Furthermore, requires Parkin limit extent cGAS-STING activation suppress I interferon (IFN). HTLV-1-transformed T cell lines PBMCs from HAM/TSP patients exhibit hallmarks chronic mitophagy which may contribute immune evasion pathogenesis. Collectively, our findings suggest manipulation represents new strategy.

Language: Английский

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Eastern Equine Encephalitis Virus: The Importance of Metabolism and Aging

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13318 - 13318

Published: Dec. 12, 2024

Eastern equine encephalitis virus (EEEV) is a mosquito-transmitted alphavirus that, among humans, can cause severe and often fatal illness. The zoonotic EEEV enzootic cycle involves of transmission between Culiseta melanura avian hosts, frequently resulting in spillover to dead-end vertebrate hosts such as humans horses. Interestingly, it has been described that the W132G mutation very low-density lipoprotein receptor (VLDLR), EEEV, significantly enhanced VLDLR-mediated cell attachment EEEV. patient’s metabolism plays pivotal role shaping complex landscape viral zoonosis. represents significant public health concern due its clinical outcomes, challenging epidemiological characteristics, certain risk factors heighten susceptibility specific populations or age groups. Age one several predictors impact outcome infection; juvenile animals appear be particularly vulnerable disease. This also observed natural infections, children are most severely impacted humans. aim this piece shed light on intricate relationship human virus.

Language: Английский

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