Mitochondrial Abnormalities in Patients with HIV-HCV Co-infection as Compared to Patients with HCV Mono-infection

Chapplain, Jean-Marc; Tattevin, Pierre; Guyader, Dominique; Bégué, Jean-Marc; Beillot, J.; Turlin, Bruno; Souala, Faouzi; Arvieux, Cédric; Rochcongar, P.; Michelet, Christian

doi:10.1310/hct1201-54

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…Two possible explanations for the non-significant changes in TAOs among all groups are: 1) induction of antioxidant mechanisms because of the disease to counteract the generated oxidative stressors, and 2) the increases in the highly antioxidant bilirubin in patients. TAOs and MDA showed a significant negative correlation in HCV-NE patients similar to previous studies [6,9,11,28]. In the cirrhotic patients, there was a positive significant correlation between TAOs and total peroxides.…”

Section: Discussionsupporting

confidence: 88%

“…HCV infection induces transcriptional downregulations that affects mainly mitochondrial respiratory chain complex core subunit genes. This induces metabolic reprogramming and aerobic glycolysis with lactate accumulation and enhanced generation of reactive oxygen species [11,16]. HCV viral-protein expression and infection severely impair mitochondrial oxidative phosphorylation leading to major reliance on nonoxidative glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…The resultant multiple areas of hypoxia increase lactate accumulation and reduce its clearance. In such a scenario, hypoxia seems to be a systemic as well as a local problem, as reflected by the induced systemic angiogenesis [11][12][13][14][15][16]. Hypoxia-induced vascular endothelial growth factors (VEGF) and their counteracting soluble receptors (sVEGFRs) are major pathophysiological players.…”

Section: Introductionmentioning

confidence: 99%

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Oxidative stress, immunological and cellular hypoxia biomarkers in hepatitis C treatment-naïve and cirrhotic patients

et al. 2021

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Introduction: Hepatitis C virus (HCV) is the main cause of chronic liver disease, with calamitous complications. Its highest rate is recorded in Egypt. This study investigated whether oxidative stress, immunological chaos and cellular hypoxia are implicated in the pathophysiology of the disease. Material and methods: This cross-sectional study aimed to evaluate the changes in blood oxidative stress, cellular hypoxia/angiogenesis and cellular immunological biomarkers in hospital-diagnosed treatment-naïve HCV-infected Upper Egyptian chronic liver disease patients vs. healthy controls (n = 40). The consecutively included patients comprised 120 with normal serum enzymes (HCV-NE) and 130 with high serum enzymes (HCV-HE), along with 120 cirrhotic patients. Results: Oxidative stress biomarkers-malondialdehyde (MDA), total peroxides and oxidative stress index (OSI)-were significantly lower in controls vs. each of the patient groups. Cirrhotic patients presented the highest levels. However, total antioxidants (TAO) showed non-significant differences among the four groups. The cellular hypoxia/angiogenesis biomarkers-lactate, vascular endothelial cell growth factor (VEGF) and its soluble receptor 1 (sVEG-FR1)-vs. controls were massively increased in patient groups. VEGF was lowest while sVEGFR1 was highest among cirrhotic patients. Immunological biomarkers,-granulocyte/monocyte-colony stimulating factor (GM-CSF) and total immunoglobulin G (IgG)-were massively increased in patient groups vs. controls. GM-CSF was lowest in HCV-HE and IgG was highest in cirrhotic patients. sVEGFR1 correlated with the progression towards cirrhosis. Conclusions: Oxidative stress is implicated in the progress of HCV infection with marked induction of cellular hypoxia and dysfunctional angiogenesis, and a futile immunological reaction. sVEGFR1 level correlated with progression towards HCV-induced liver fibrosis.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxidative stress, immunological and cellular hypoxia biomarkers in hepatitis C treatment-naïve and cirrhotic patients

et al. 2021

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“…Although this is the first time that alterations on respiratory complexes are investigated in SinV infection, it was shown recently that patients infected with hepatitis C virus and HIV presented alterations on liver mitochondrial respiratory functions due to a decrease in Complex IV (CIV) activity [44]. Since CI- and CII-dependent ETS capacity deteriorated as SinV infection progresses and was severely compromised at 24 h, a defect on CIV might be suggested [34].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Bioenergetic Alterations in Mouse Neuroblastoma Cells Infected with Sindbis Virus: Implications to Viral Replication and Neuronal Death

et al. 2012

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The metabolic resources crucial for viral replication are provided by the host. Details of the mechanisms by which viruses interact with host metabolism, altering and recruiting high free-energy molecules for their own replication, remain unknown. Sindbis virus, the prototype of and most widespread alphavirus, causes outbreaks of arthritis in humans and serves as a model for the study of the pathogenesis of neurological diseases induced by alphaviruses in mice. In this work, respirometric analysis was used to evaluate the effects of Sindbis virus infection on mitochondrial bioenergetics of a mouse neuroblastoma cell lineage, Neuro 2a. The modulation of mitochondrial functions affected cellular ATP content and this was synchronous with Sindbis virus replication cycle and cell death. At 15 h, irrespective of effects on cell viability, viral replication induced a decrease in oxygen consumption uncoupled to ATP synthesis and a 36% decrease in maximum uncoupled respiration, which led to an increase of 30% in the fraction of oxygen consumption used for ATP synthesis. Decreased proton leak associated to complex I respiration contributed to the apparent improvement of mitochondrial function. Cellular ATP content was not affected by infection. After 24 h, mitochondria dysfunction was clearly observed as maximum uncoupled respiration reduced 65%, along with a decrease in the fraction of oxygen consumption used for ATP synthesis. Suppressed respiration driven by complexes I- and II-related substrates seemed to play a role in mitochondrial dysfunction. Despite the increase in glucose uptake and glycolytic flux, these changes were followed by a 30% decrease in ATP content and neuronal death. Taken together, mitochondrial bioenergetics is modulated during Sindbis virus infection in such a way as to favor ATP synthesis required to support active viral replication. These early changes in metabolism of Neuro 2a cells may form the molecular basis of neuronal dysfunction and Sindbis virus-induced encephalitis.

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“…For example, the core protein of HCV reduces the activity of electron transport protein Cx I and stimulates the production of ROS in liver mitochondria . Similarly, patients coinfected with HIV and HCV display more serious metabolic aberrations in liver mitochondria due to compromised Cx IV activity than do patients infected with HCV alone . Similarly, infection with rabies virus increases the activity of Cx I and Cx IV in neurons , and an increase in Cx I activity correlates with susceptibility to rabies virus infection and the presence of a rabies virus phosphoprotein, together with mitochondrial dysfunction and ROS generation .…”

Section: Discussionmentioning

confidence: 99%

Cellular proteomic analysis of porcine circovirus type 2 and classical swine fever virus coinfection in porcine kidney‐15 cells using isobaric tags for relative and absolute quantitation‐coupled LC‐MS/MS

et al. 2017

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Viral coinfection or superinfection in host has caused public health concern and huge economic losses of farming industry. The influence of viral coinfection on cellular protein abundance is essential for viral pathogenesis. Based on a coinfection model for porcine circovirus type 2 (PCV2) and classical swine fever virus (CSFV) developed previously by our laboratory, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled LC-MS/MS proteomic profiling was performed to explore the host cell responses to PCV2-CSFV coinfection. Totally, 3932 proteins were identified in three independent mass spectrometry analyses. Compared with uninfected cells, 304 proteins increased (fold change >1.2) and 198 decreased (fold change <0.833) their abundance in PCV2-infected cells (p < 0.05), 60 and 61 were more and less abundant in CSFV-infected cells, and 196 and 158 were more and less abundant, respectively in cells coinfected with PCV2 and CSFV. Representative differentially abundant proteins were validated by quantitative real-time PCR, Western blotting and confocal laser scanning microscopy. Bioinformatic analyses confirmed the dominant role of PCV2, and indicated that mitochondrial dysfunction, nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated oxidative stress response and apoptosis signaling pathways might be the specifical targets during PCV2-CSFV coinfection.

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Mitochondrial Abnormalities in Patients with HIV-HCV Co-infection as Compared to Patients with HCV Mono-infection

Abstract: HCV has deleterious effects on liver mitochondrial metabolism, notably on respiratory chain complex IV. No significant interaction with HIV was observed.

Cited by 6 publications

References 33 publications

Oxidative stress, immunological and cellular hypoxia biomarkers in hepatitis C treatment-naïve and cirrhotic patients

Oxidative stress, immunological and cellular hypoxia biomarkers in hepatitis C treatment-naïve and cirrhotic patients

Mitochondrial Bioenergetic Alterations in Mouse Neuroblastoma Cells Infected with Sindbis Virus: Implications to Viral Replication and Neuronal Death

Cellular proteomic analysis of porcine circovirus type 2 and classical swine fever virus coinfection in porcine kidney‐15 cells using isobaric tags for relative and absolute quantitation‐coupled LC‐MS/MS

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