Binding of human lipoproteins (low, very low, high density lipoproteins) to recombinant envelope proteins of hepatitis C virus

Monazahian, Masyar; Kippenberger, Serena; Müller, Anke; Seitz, H.; Böhme, Ingo; Grethe, Stefanie; Thomssen, R.

doi:10.1007/s004300000032

Cited by 64 publications

(73 citation statements)

References 33 publications

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“…6,18,19 The LDL-R has also been shown to play a role in HCV infection. 6 Wild-type HCV particles were found to be associated with LDL and vLDL in blood, [6][7][8] suggesting that the virus might "hitch a ride" into hepatocytes by binding to LDL. Loss of LDL receptor expression in primary cultured hepatocytes might account for the difficulty of infecting the cells with wild-type HCV (bound to LDL) in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…6 The HCV surface receptors, glycoproteins E1 and E2, have been shown to associate with LDL and vLDL. 7 The virus particle itself was shown to associate with the LDL-R expressed on HepG2 cells. 6,8 These results suggest that HCV might use the LDL-R to enter the cell and escape degradation.…”

mentioning

confidence: 99%

“…6 The HCV surface receptors, glycoproteins E1 and E2, have been shown to associate with LDL and vLDL. 7 The virus particle itself was shown to associate with the …”

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confidence: 99%

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Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes

et al. 2006

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Low-density lipoprotein (LDL) is an important carrier of plasma cholesterol and triglycerides whose concentration is regulated by the liver parenchymal cells. Abnormal LDL regulation is thought to cause atherosclerosis, while viral binding to LDL has been suggested to facilitate hepatitis C infection. Primary hepatocytes quickly lose the ability to clear LDL during in vitro culture. Here we show that the coculture of hepatocytes with liver sinusoidal endothelial cells (LSEC) significantly increases the ability of hepatocytes to uptake LDL in vitro. LDL uptake does not increase when hepatocytes are cocultured with other cell types such as fibroblasts or umbilical vein endothelial cells. We find that LSECs induce the hepatic expression of the LDL receptor and the epidermal growth factor receptor. In addition, while hepatocytes in single culture did not take up hepatitis C virus (HCV)-like particles, the hepatocytes cocultured with LSECs showed a high level of HCV-like particle uptake. We suggest that coculture with LSECs induces the emergence of a sinusoidal surface in primary hepatocytes conducive to the uptake of HCV-like particles. In conclusion, our findings describe a novel model of polarized hepatocytes in vitro that can be used for the study of LDL metabolism and hepatitis C infection. L ow-density lipoprotein (LDL) is a plasma-carried particle whose lipid component includes cholesterol and triglycerides. 1 LDL originates from very low-density lipoprotein (vLDL) synthesized by the liver with apoprotein B-100. The vLDL is converted to LDL by an endothelial lipase, which releases free fatty acids, increasing the density of the particle to form LDL. Excess LDL is then taken up by hepatocytes through LDL receptor (LDL-R)-mediated endocytosis. 1 Improper hepatic clearance of LDL results in elevated plasma levels of LDL which is a serious risk factor for the development of atherosclerosis. 2 One of the first steps in atherosclerosis is the passage of LDL into the vascular wall. Once trapped in the vessel wall, LDL can undergo oxidation. 3 Oxidized LDL is no longer a ligand for the LDL receptor. 4 Accumulation of oxidized LDL and LDL aggregates in the vessel wall stimulates an inflammatory response causing endothelial injury, macrophage recruitment, foam cell formation, and smooth muscle cell proliferation. 3 Current therapeutic intervention includes administration of statins, which block cholesterol production and increase expression of the LDL-R by the liver parenchymal cells, 2 removing LDL from circulation. 5 In addition, liver sinusoidal endothelial cells (LSECs) remove oxidized LDL from the circulation via the scavenger cell receptor. 5 LDL-and LDL-R-mediated pathways have also been shown to play a role in hepatitis C virus (HCV) infection. 6 The HCV surface receptors, glycoproteins E1 and E2, have been shown to associate with LDL and vLDL. 7 The virus particle itself was shown to associate with the

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes

et al. 2006

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“…In addition, lipoproteins play an important role in the process of HCV infection since complexing of the virus to the low-density lipoprotein (VLDL-C) or LDL-C could promote endocytosis of HCV via the LDL receptor (Agnello et al, 1999). HCV infection and hypobetalipoproteinemia is characteristic in patients with HCV infection (Monazahian et al, 1999;Monazahian et al, 2000;Perlemuter et al, 2002). There are a lower cholesterol (total cholesterol, HDL-C and LDL-C) and a lower triglycerides (TG) levels in CHC patients than those of normal subjects Siagris et al, 2006).…”

Section: Metabolic Disordersmentioning

confidence: 99%

Metabolic Aspects of Hepatitis C Virus Infection

Huang¹,

Yu²,

Dai³

et al. 2012

Molecular Virology

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“…La infección persistente parece ser debida a diversas estrategias virales de evasión y modificación de la respuesta inmune, como la variación antigénica, la asociación de las partículas virales con β-lipoproteínas y la infección de células del sistema inmune como linfocitos B y células dendríticas (3)(4)(5)(6).…”

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Producción y purificación de la proteína core del virus de la hepatitis C en el sistema de expresión del baculovirus para ensayos biológicos.

Rubio¹,

Cómbita²,

Ortiz-Reyes³

et al. 2005

biomedica

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Introducción. La infección por el virus de la hepatitis C (VHC) se caracteriza por la alta frecuencia de infección persistente. La capacidad del VHC para inducir alteraciones en la función de las células del sistema inmune, específicamente en las células dendríticas, parece ser una de las estrategias virales implicada en el establecimiento de la infección persistente. Esta estrategia parece estar mediada en gran parte por una de las proteínas estructurales codificada por el genoma del VHC, la proteína Core, unidad estructural de la cápside viral. Objetivo. Una de las limitantes para la evaluación de las propiedades de Core es la obtención y la purificación de la proteína nativa (191 aa). El objetivo de este estudio fue la producción y la purificación de la proteína Core completa en un sistema eucariote para evaluar las propiedades de la proteína en cultivos de células dendríticas humanas. Resultados. En este estudio se logró la producción de la proteína Core completa en el sistema de expresión de baculovirus y su purificación por la técnica de separación por punto isoeléctrico y electroelución. La pureza de la proteína obtenida se confirmó por Western blot y tinción con plata. Estos análisis mostraron dos bandas únicas correspondientes a las isoformas p23 y p21 de la proteína Core, previamente descritas en la literatura. Conclusiones. La proteína obtenida posee varias de las condiciones de la proteína Core nativa, como peso molecular, isoformas y localización subcelular. Los procedimientos descritos en este artículo son aplicables a proteínas asociadas a membranas producidas en sistemas de expresión eucarióticos. Palabras clave: virus de la hepatitis C, proteína Core, Baculovirus, sistema de expresión, isoelectroenfoque, purificación.Hepatitis C virus core protein production and purification in a baculovirus expression system for biological assays Background. The hepatitis C virus (HCV) commonly causes persistent infection. One of the viral mechanisms in preventing viral clearance is the ability of HCV to induce functional alterations of the immune system cells, specifically of dendritic cells. Viral proteins producing the dendritic cell functional alterations have been identified as the HCV core protein, which makes up the capsid structural unit. Objective. One of the limitations to evaluate core protein properties is the difficulty in obtaining and purifying the complete protein -consisting of 191 amino acids. The aim of the current study was to produce and purify the recombinant core protein in a eukaryotic system, and to evaluate its effect in human dendritic cell cultures. Results. The core protein p23 isoform was expressed in a baculovirus system and purified using isoelectric point separation and electroelution. The purity of the core protein was confirmed by silver stain and Western blot. These analyses showed the presence of two bands that correspond to p23 and p21 isoforms of core protein as previously reported. Conclusion. The expressed protein differed from naive core protein is terms of molecular we...

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Binding of human lipoproteins (low, very low, high density lipoproteins) to recombinant envelope proteins of hepatitis C virus

Cited by 64 publications

References 33 publications

Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes

Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes

Metabolic Aspects of Hepatitis C Virus Infection

Producción y purificación de la proteína core del virus de la hepatitis C en el sistema de expresión del baculovirus para ensayos biológicos.

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