bims-mevinf 2024-11-17 papers

Fish Shellfish Immunol. 2024 Nov 09. pii: S1050-4648(24)00665-X. [Epub ahead of print]155 110020

Grass Carp Reovirus (GCRV) infection activates the PERK-eIF2α pathway to promote the viral replication.

Zeen Shen, Yanling Qi, Wenbin Yu, Song Li, Zhuo Liu, Liuyang Li, Min Zhu, Chengliang Gong, Xiaolong Hu.

Grass carp reovirus (GCRV) belongs to the genus Aquareovirus and is responsible for causing serious hemorrhagic disease in grass carp (Ctenopharyngodon idella), characterized by high mortality rates. Numerous animal viruses have been shown to activate endoplasmic reticulum stress (ERS). However, the potential for GCRV infection to induce ERS and its implications for viral infection remain unclear. In this study, we demonstrated that GCRV infection induces ERS, activates the protein kinase R-like ER kinase (PERK) pathway, and inhibits both the inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6) pathways within the unfolded protein response (UPR). Additionally, we modulated the levels of ERS and UPR pathways in CIK cells through drug treatment and small interfering RNAs (siRNAs). Our findings revealed that the onset of ERS accelerated GCRV infection, while the ATF6 and IRE1 pathways within the UPR negatively regulated GCRV infection. Conversely, the PERK pathway facilitated GCRV infection. Furthermore, we showed that GCRV infection induced oxidative stress, with the production of reactive oxygen species (ROS) being positively regulated by the PERK pathway and the downstream gene endoplasmic reticulum oxidoreductase-1α (ERO1α). Notably, ROS promoted GCRV infection. Collectively, our findings indicate that GCRV infection activates ERS, which in turn promotes viral infection through the PERK-ERO1α-ROS signaling pathway. Thus, the PERK pathway may serve as a novel antiviral target for the prevention of GCRV infection.

Keywords: Endoplasmic reticulum stress; GCRV; Grass carp; PERK pathway

DOI: https://doi.org/10.1016/j.fsi.2024.110020

Cells. 2024 Oct 29. pii: 1789. [Epub ahead of print]13(21):

Mitochondrial Dysfunction and Metabolic Disturbances Induced by Viral Infections.

Sandra E Pérez, Monika Gooz, Eduardo N Maldonado.

Viruses are intracellular parasites that utilize organelles, signaling pathways, and the bioenergetics machinery of the cell to replicate the genome and synthesize proteins to build up new viral particles. Mitochondria are key to supporting the virus life cycle by sustaining energy production, metabolism, and synthesis of macromolecules. Mitochondria also contribute to the antiviral innate immune response. Here, we describe the different mechanisms involved in virus-mitochondria interactions. We analyze the effects of viral infections on the metabolism of glucose in the Warburg phenotype, glutamine, and fatty acids. We also describe how viruses directly regulate mitochondrial function through modulation of the activity of the electron transport chain, the generation of reactive oxygen species, the balance between fission and fusion, and the regulation of voltage-dependent anion channels. In addition, we discuss the evasion strategies used to avoid mitochondrial-associated mechanisms that inhibit viral replication. Overall, this review aims to provide a comprehensive view of how viruses modulate mitochondrial function to maintain their replicative capabilities.

Keywords: VDACs; Warburg; electron transport chain; fatty acids; glucose; glutamine; innate immunity; metabolic reprogramming; mitochondria; reactive oxygen species; virus

DOI: https://doi.org/10.3390/cells13211789

Cell Mol Biol Lett. 2024 Nov 08. 29(1): 138

The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death.

Jiufeng Xie, Cui Yuan, Sen Yang, Zhenling Ma, Wenqing Li, Lin Mao, Pengtao Jiao, Wei Liu.

Coronavirus disease 2019 (COVID-19) represents the novel respiratory infectious disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by rapid spread throughout the world. Reactive oxygen species (ROS) account for cellular metabolic by-products, and excessive ROS accumulation can induce oxidative stress due to insufficient endogenous antioxidant ability. In the case of oxidative stress, ROS production exceeds the cellular antioxidant capacity, thus leading to cell death. SARS-CoV-2 can activate different cell death pathways in the context of infection in host cells, such as neutrophil extracellular trap (NET)osis, ferroptosis, apoptosis, pyroptosis, necroptosis and autophagy, which are closely related to ROS signalling and control. In this review, we comprehensively elucidated the relationship between ROS generation and the death of host cells after SARS-CoV-2 infection, which leads to the development of COVID-19, aiming to provide a reasonable basis for the existing interventions and further development of novel therapies against SARS-CoV-2.

Keywords: Antiviral therapy; COVID-19; Cell death; Reactive oxygen species; SARS-CoV-2

DOI: https://doi.org/10.1186/s11658-024-00659-6

Int J Biol Macromol. 2024 Nov 09. pii: S0141-8130(24)08293-X. [Epub ahead of print] 137484

1α,25-hydroxyvitamin D3 alleviated rotavirus infection induced ferroptosis in IPEC-J2 cells by regulating the ATF3-SLC7A11-GPX4 axis.

Ye Zhao, Xiaoxiao Zhu, Qingyuan Lan, Ziang Wei, Pan Shang, Lei Song, Shijie Hu, Lei Chen, Mailin Gan, Lili Niu, Yan Wang, Linyuan Shen, Li Zhu.

Rotavirus (RV) mainly infects mature intestinal epithelial cells and impairs intestinal absorption function, which leads to the death of infected cells and eventually fatal diarrhea. Ferroptosis is a novel regulatory cell death pattern, which can be caused by virus infection. 1α,25-hydroxyvitamin D3 (1,25D3) has an anti-RV infection effect and can regulate ferroptosis. However, whether RV infection can induce ferroptosis, and whether 1,25D3 can inhibit RV infection by regulating ferroptosis has not yet been studied. Present study shows that RV infection or erastin treatment induces IPEC-J2 cell death, which results in mitochondrial shrinkage, decreased mitochondrial membrane potential (MMP) and glutathione (GSH) content, increased MMP, intracellular Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA) contents. Meanwhile, ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1), and deferoxamine (DFO) treatment can effectively reverse the increase of intracellular Fe2+, ROS and MDA levels induced by RV infection. Moreover, RV infection increases activating transcription factor 3 (ATF3) mRNA and protein expressions, and inhibited SLC7A11 and glutathione peroxidase 4 (GPX4) expressions, which was partially alleviated by siATF3. 1,25D3 treatment significantly eliminates RV induced ferroptosis via ATF3-SLC7A11-GPX4 axis. Therefore, our results reveals that RV infection induces ferroptosis in IPEC-J2 cell and 1,25D3 alleviates RV induced ferroptosis by regulating the ATF3-SLC7A11-GPX4 axis.

Keywords: 1α,25-hydroxyvitamin D(3); ATF3-SLC7A11-GPX4 axis; Ferroptosis; IPEC-J2 cell; Rotavirus

DOI: https://doi.org/10.1016/j.ijbiomac.2024.137484

Pulm Circ. 2024 Oct;14(4): e70009

The metabolic and physiologic impairments underlying long COVID associated exercise intolerance.

Brooks P Leitner, Phillip Joseph, Andres Figueroa Quast, Maria Alejandra Ramirez, Paul M Heerdt, Jose G Villalobos, Inderjit Singh.

Data from invasive CPET (iCPET) revealed long COVID patients have impaired systemic oxygen extraction (EO2), suggesting impaired mitochondrial ATP production. However, it remains uncertain whether the initial severity of SARS-CoV-2 infection has implications on EO2 and exercise capacity (VO2) nor has there been assessment of anerobic ATP generation in long COVID patients. iCPET was performed on 47 long COVID patients (i.e., full cohort; n = 8 with severe SARS-CoV-2 infection). In a subset of patients (i.e., metabolomic cohort; n = 26) metabolomics on venous and arterial blood samples during iCPET was performed. In the full cohort, long COVID patients exhibited reduced peak EO2 with reduced peak VO2 (90 ± 17% predicted) relative to cardiac output (118 ± 23% predicted). Peak VO2 [88% predicted (IQR 81% - 108%) vs. 70% predicted (IQR 64% - 89%); p = 0.02] and EO2 [0.59(IQR 0.53-0.62) vs. 0.53(IQR 0.50-0.48); p = 0.01) were lower in severe versus mild infection. In the metabolomic cohort, 12 metabolites were significantly consumed, and 41 metabolites were significantly released (p-values < 0.05). Quantitative metabolomics demonstrated significant increases in inosine and succinate arteriovenous gradients during exercise. Peak VO2 was significantly correlated with peak venous succinate (r = 0.68; p = 0.0008) and peak venous lactate (r = 0.49; p = 0.0004). Peak EO2 and consequently peak VO2 impact long COVID patients in a severity dependent manner. Exercise intolerance associated with long COVID is defined by impaired aerobic and anaerobic energy production. Peak venous succinate may serve as a potential biomarker in long COVID.

Keywords: PASC; invasive CPET; long COVID; metabolomic

DOI: https://doi.org/10.1002/pul2.70009