High level of serum cholesteryl ester transfer protein in active hepatitis C virus infection

Satoh, Keisuke; Nagano, Tomohisa; Seki, Nobuyoshi; Tomita, Yoichi; Aida, Yuta; Sugita, Tomonori; Itagaki, Munenori; Sutoh, Satoshi; Abe, Hiroshi; Aizawa, Yoshifusa

doi:10.4254/wjh.v8.i5.291

Cited by 8 publications

(6 citation statements)

References 39 publications

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“…CL is subsequently redistributed amongst all apoB lipoprotein classes by cholesteryl ester transfer protein (CETP) activity, mediating CL transfer from HDL to apoB containing lipoproteins as well, which are subsequently trafficked back to the liver 32 . CETP is increased in active HCV infection 33 . Up-regulated reverse cholesterol transport to the liver may be a compensatory homeostatic response to decreased endogenous cholesterol synthesis in HCV-G3 infection.…”

Section: Discussionmentioning

confidence: 99%

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Sheridan

Shawa

Thomas

et al. 2022

Sci Rep

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Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3.

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Section: Discussionmentioning

confidence: 99%

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Sheridan

Shawa

Thomas

et al. 2022

Sci Rep

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“…Among them, CETP was up-regulated in the serum of asymptomatic individuals, as previously seen in COVID-19 patients with mild symptoms (Liu et al 2021 ), while in the serum of critical patients this protein appeared down-regulated (Shu et al 2020 ). CETP mediates lipid exchange (Satoh et al 2016 ), but it also inhibits prolonged inflammation. Thus, CETP upregulation might correlate with the alteration of lipids after viral infection (membrane fusion, vesicles, etc.)…”

Section: Discussionmentioning

confidence: 99%

The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo

Beltrán-Camacho

Eslava-Alcon

Rojas-Torres

et al. 2022

Mol Med

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 million deaths worldwide. While asymptomatic individuals are responsible of many potential transmissions, the difficulty to identify and isolate them at the high peak of infection constitutes still a real challenge. Moreover, SARS-CoV-2 provokes severe vascular damage and thromboembolic events in critical COVID-19 patients, deriving in many related deaths and long-hauler symptoms. Understanding how these processes are triggered as well as the potential long-term sequelae, even in asymptomatic individuals, becomes essential. Methods We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum from COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Healthy CACs were incubated ex-vivo with the serum of either COVID-19 negative (PCR −/IgG −, n:8) or COVID-19 positive asymptomatic donors, at different infective stages: PCR +/IgG − (n:8) and PCR −/IgG + (n:8). Also, a label free quantitative approach was applied to identify and quantify protein differences between these serums. Finally, machine learning algorithms were applied to validate the differential protein patterns in CACs. Results Our results confirmed that SARS-CoV-2 promotes changes at the protein level in the serum of infected asymptomatic individuals, mainly correlated with altered coagulation and inflammatory processes (Fibrinogen, Von Willebrand Factor, Thrombospondin-1). At the cellular level, proteins like ICAM-1, TLR2 or Ezrin/Radixin were only up-regulated in CACs treated with the serum of asymptomatic patients at the highest peak of infection (PCR + /IgG −), but not with the serum of PCR −/IgG + individuals. Several proteins stood out as significantly discriminating markers in CACs in response to PCR or IgG + serums. Many of these proteins particiArticle title: Kindly check and confirm the edit made in the article title.pate in the initial endothelial response against the virus. Conclusions The ex vivo incubation of CACs with the serum of asymptomatic COVID-19 donors at different stages of infection promoted protein changes representative of the endothelial dysfunction and inflammatory response after viral infection, together with activation of the coagulation process. The current approach constitutes an optimal model to study the response of vascular cells to SARS-CoV-2 infection, and an alternative platform to test potential inhibitors targeting either the virus entry pathway or the immune responses following SARS-CoV-2 infection.

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“…Down-regulation of this protein has been observed in many viral infections . Cholesteryl ester transfer protein (CETP) can mediate the exchange of CE in HDL to TG in other lipoproteins . It is speculated that the up-regulation of CETP may be due to the important role of lipids in virus infection.…”

Section: Discussionmentioning

confidence: 99%

Proteomics Analysis of Serum from COVID-19 Patients

Liu

Cao

et al. 2021

ACS Omega

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Coronavirus disease 2019 (COVID-19) is a worldwide pandemic. To understand the changes in plasma proteomics upon SARS-CoV-2 infection, we analyzed the protein profiles of plasma samples from 10 COVID-19 patients and 10 healthy volunteers by using the DIA quantitative proteomics technology. We compared and identified differential proteins whose abundance changed upon SARS-CoV-2 infection. Bioinformatic analyses were then conducted for these identified differential proteins. The GO/KEEG database was used for functional annotation and enrichment analysis. The interaction relationship of differential proteins was evaluated with the STRING database, and Cytoscape software was used to conduct network analysis of the obtained data. A total of 323 proteins were detected in all samples. Difference between patients and healthy donors was found in 44 plasma proteins, among which 36 proteins were up-regulated and 8 proteins were down-regulated. GO functional annotation showed that these proteins mostly composed of cellular anatomical entities and proteins involved in biological regulation, cellular processes, transport, and other processes. KEEG functional annotation further showed that these proteins were mainly involved in complement system activation and infectious disease processes. Importantly, a KEEG pathway (natural killer cell-mediated cytotoxicity) was enriched, with three important activators of this pathway, ICAM1/2 and IgG, being up-regulated. Protein–protein interaction (PPI) statistics indicated that, among these 44 proteins, 6 were the most significantly up-regulated (DBH, SHGB, TF, ICAM2, THBS1, and C1RL) while 2 were the most significantly down-regulated (APCS and ORM1). Results from this study showed that a few proteins associated with immune activation were up-regulated in patient plasma. In addition, this study established a method for extraction and quantitative determination of plasma components in convalescent plasma from COVID-19 patients.

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High level of serum cholesteryl ester transfer protein in active hepatitis C virus infection

Abstract: Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.

Cited by 8 publications

References 39 publications

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo

Proteomics Analysis of Serum from COVID-19 Patients

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