Abstract:
BACKGROUND & AIMS:In the sera of infected patients, hepatitis C virus (HCV) particles display heterogeneous forms with low-buoyant densities (<1.08), underscoring their lipidation via association with apoB-containing lipoproteins, which was proposed to occur during assembly or secretion from infected hepatocytes. However, the mechanisms inducing this association remain poorly-defined and most cell culture grown HCV (HCVcc) particles exhibit higher density (>1.08) and poor/no association with apoB. We aimed to elucidate the mechanisms of lipidation and to produce HCVcc particles resembling those in infected sera. METHODS:We produced HCVcc particles of Jc1 or H77 strains from Huh-7.5 hepatoma cells cultured in standard conditions (10%-fetal calf serum) vs. in serum-free or human serum conditions before comparing their density profiles to patient-derived virus. We also characterized wild-type and Jc1/H77 hypervariable region 1 (HVR1)-swapped mutant HCVcc particles produced in serum-free media and incubated with different serum types or with purified lipoproteins. RESULTS:Compared to serum-free or fetal calf serum conditions, production with human serum redistributed most HCVcc infectious particles to low density (<1.08) or very-low density (<1.04) ranges. In addition, short-time incubation with human serum was sufficient to shift HCVcc physical particles to low-density fractions, in time- and dose-dependent manners, which increased their specific infectivity, promoted apoB-association and induced neutralization-resistance. Moreover, compared to Jc1, we detected higher levels of H77 HCVcc infectious particles in very-low-density fractions, which could unambiguously be attributed to strain-specific features of the HVR1 sequence. Finally, all 3 lipoprotein classes, i.e., very-low-density, low-density and high-density lipoproteins, could synergistically induce low-density shift of HCV particles; yet, this required additional non-lipid serum factor(s) that include albumin. CONCLUSIONS:The association of HCV particles with lipids may occur in the extracellular milieu. The lipidation level depends on serum composition as well as on HVR1-specific properties. These simple culture conditions allow production of infectious HCV particles resembling those of chronically-infected patients. LAY SUMMARY:Hepatitis C virus (HCV) particles may associate with apoB and acquire neutral lipids after exiting cells, giving them low-buoyant density. The hypervariable region 1 (HVR1) is a majorviral determinant of E2 that controls this process. Besides lipoproteins, specific serum factors including albumin promote extracellular maturation of HCV virions. HCV particle production in vitro, with media of defined serum conditions, enables production of infectious particles resembling those of chronically infected patients.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Denolly S,Granier C,Fontaine N,Pozzetto B,Bourlet T,Guérin M,Cosset FLdoi
10.1016/j.jhep.2018.11.033subject
Has Abstractpub_date
2019-04-01 00:00:00pages
626-638issue
4eissn
0168-8278issn
1600-0641pii
S0168-8278(18)32619-9journal_volume
70pub_type
杂志文章abstract:BACKGROUND/AIMS:Type 2 autoimmune hepatitis (AIH) is characterized by the presence of anti-liver kidney microsome (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. However, the correlation between these autoantibodies and the genetic background has not been studied. METHODS:Frequencies of HLA cl...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.07.034
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND/AIM:Smooth muscle antibodies and antinuclear antibodies characterize type 1 autoimmune hepatitis. Our aim was to correlate the appearance and disappearance of these autoantibodies with clinical and histological events. METHODS:One hundred and seven patients were evaluated successively over 128+/-9 months. A...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80096-8
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND/AIMS:Central nervous system abnormalities such as fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in many other causes of chronic liver disease. The finding that fatigue is unrelated to activity of hepatitis or mode of infection could indicate an independent eff...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00172-1
更新日期:2002-09-01 00:00:00
abstract:BACKGROUND/AIMS:The oral administration of the major transplant immunosuppressants cyclosporine A and tacrolimus leads to unpredictable drug levels requiring drug monitoring. Hepatic and extrahepatic metabolism of cyclosporine A and tacrolimus by cytochrome P450 proteins has been analyzed but metabolism and inactivatio...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00040-x
更新日期:2001-06-01 00:00:00
abstract::The clinical course of cirrhosis is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation and activation of systemic inflammation. Different disease states, encompassing compensated and decompensated cirrhosis and a late decompensated state, are related...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2017.10.020
更新日期:2018-03-01 00:00:00
abstract::Chronic cholestatic diseases, whether occurring in infancy, childhood or adulthood, are characterized by defective bile acid transport from the liver to the intestine, which is caused by primary damage to the biliary epithelium in most cases. In this article, approaches to diagnosis and management of the main specific...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(00)80421-3
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND/AIMS:The finer branches of the biliary tree play an important role in biliary regeneration. They are consistently escorted by microvessels. Defects in the vascularization of these structures could impair bile duct regeneration. Therefore, we investigated the pattern of the escorting microvessels during the d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.08.011
更新日期:2006-05-01 00:00:00
abstract::The present study was conducted to evaluate if the increased rate of apoptosis previously reported in the liver of ethanol-treated rats was accompanied by increased cell renewal. A quantitative analysis of apoptosis was performed in rats fed an ethanol-containing liquid diet for 5 weeks. S-phase cells were demonstrate...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80498-2
更新日期:1994-04-01 00:00:00
abstract:BACKGROUND & AIMS:The accuracy of creatinine-based estimated GFR (eGFR) in assessing the prevalence of chronic kidney disease (CKD) and associated mortality after liver transplantation (LTx) is unknown. Using measured GFR (mGFR) by iothalamate clearance, we determined the prevalence of the entire spectrum of renal dysf...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.03.034
更新日期:2014-08-01 00:00:00
abstract::We have studied the roles of immunoprophylaxis, patient selection policy and coexistent hepatitis D virus infection in the outcome of 56 HBsAg-positive elective liver transplant recipients. Twenty-nine unselected patients not treated with immunoprophylaxis formed group 1 and were compared to a recent consecutive serie...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(05)80396-4
更新日期:1994-08-01 00:00:00
abstract::Familial hypobetalipoproteinemia (FHBL) is an monogenic co-dominant disorder characterized by reduced plasma levels of cholesterol, low density lipoproteins (LDL) and apolipoprotein B (apoB) often associated with non-alcoholic fatty liver disease (NAFLD). It has been suggested that FHBL might predispose to gallstone d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.03.012
更新日期:2005-07-01 00:00:00
abstract::It has been postulated that one of the mechanisms of hypotension associated with cirrhosis is an attenuated responsiveness to catecholamines despite the increased activity of the sympathetic nervous system and the elevated plasma concentrations of the sympathetic neurotransmitter, norepinephrine. This abnormality was ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80531-8
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND & AIMS:Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. However, there are limited data on the prevalence and short-term outcomes of ACLF in patients with cirrhosis seen in the US...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.12.018
更新日期:2019-04-01 00:00:00
abstract::Hepatitis A virus (HAV) infection in adults is often symptomatic and disabling. The present article summarizes our experience with phase 2 studies of an inactivated hepatitis A virus vaccine. Pre- and post-exposure prophylaxis with immune globulin (IG) is only effective for 4-6 months. We compared the safety, tolerabi...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0168-8278(05)80375-7
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND & AIMS:Regulatory CD4(+) T cells (Tregs) are considered to affect outcomes of HCV infection, because they increase in number during chronic hepatitis C and can suppress T-cell functions. METHODS:Using microarray analysis, in situ immunofluorescence, ELISA, and flowcytometry, we characterised functional diff...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.04.011
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatocytes differentiated from human embryonic stem cells (hESCs) have the potential to overcome the shortage of primary hepatocytes for clinical use and drug development. Many strategies for this process have been reported, but the functionality of the resulting cells is incomplete. We hypothesize t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.02.028
更新日期:2016-06-01 00:00:00
abstract::The possible aggravation of liver injury by impaired cellular antioxidant function was investigated. A vitamin E-deficient diet (0.5 mg/kg alpha-tocopherol; control 100 mg/kg) significantly reduced rat liver alpha-tocopherol concentrations after 4 weeks (1.8 +/- 1.7 micrograms/g; control 34.4 +/- 2.4 micrograms/g, p <...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80665-8
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND/AIMS:We conducted an analysis of chromosomal numerical aberrations and their clinical significance in hepatocellular carcinoma. METHODS:We analyzed 87 hepatocellular carcinomas by array-based comparative genomic hybridization with an array containing 800 bacterial artificial chromosome clones. RESULTS:Freq...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.05.033
更新日期:2005-11-01 00:00:00
abstract:BACKGROUND/AIMS:The natural history of chronic hepatitis C infection during pregnancy has not been clearly established, and thus our aim was to assess serum alanine aminotransferase levels and serum HCV RNA levels during pregnancy. METHODS:Twenty-six pregnant women with chronic hepatitis C were studied. Serum alanine ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80075-6
更新日期:2000-02-01 00:00:00
abstract::The effectiveness of recombinant alpha-interferon was evaluated in chronic non-A, non-B hepatitis of parenteral transmission. Thirty patients were randomly allocated two groups: control group (without treatment) and treatment group (alpha-interferon 5 mega units thrice weekly for 2 months, and then 1.5 mega units unti...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0168-8278(90)90166-o
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatitis C virus (HCV) has been recognized as a major cause of liver disease, but little is known about its diffusion at population level. To estimate the prevalence and incidence of HCV infection and to explore potential risk factors at population level, an epidemiologic study was carried out. METHOD...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80276-0
更新日期:1997-07-01 00:00:00
abstract::The nucleocapsid antigens (HBc and HBe) are present on the membranes of HBV-infected hepatocytes from HBV carriers. In autologous cytotoxicity experiments we demonstrate that cytotoxic T cells sensitised to the nucleocapsid proteins of hepatitis B are present in HBe antigen-positive HBV carriers with chronic hepatitis...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80004-1
更新日期:1987-02-01 00:00:00
abstract:BACKGROUND/AIMS:To compare carotid intima-media thickness (IMT) - an index of early atherosclerosis - among patients with non-alcoholic steatohepatitis (NASH), patients with chronic hepatitis B (HBV) or C (HCV) and control subjects. METHODS:We studied 60 consecutive patients with biopsy-proven NASH, 60 patients with H...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.01.021
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND/AIM:The aim of this study was to sequence the precore region of HBV isolated from serum and tumorous and non-tumorous liver tissue from patients with hepatocellular carcinoma to identify mutations that might play a role in malignant transformation. METHODS:HBV DNA was extracted from 62 sera, 14 tumorous and...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80212-2
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND/AIMS:Excessive formation of nitric oxide may mediate the generalized vasorelaxation and hyporesponsiveness to vasoconstrictors observed in portal hypertensive states. Endotoxin, released from the bowel and detoxified by the liver, could stimulate inducible nitric oxide synthase directly or indirectly via the...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80266-9
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND & AIMS:In the Netherlands, transmission of hepatitis B virus occurs mainly within behavioural high-risk groups, such as in men who have sex with men. Therefore, a vaccination programme has targeted these high-risk groups. This study evaluates the impact of the vaccination programme targeting Amsterdam's larg...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.08.002
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND/AIM:Endothelin-1 plays an important role in the regulation of portal hypertension; endothelin antagonists have been extensively studied in portal hypertensive animals. We aimed to evaluate the efficacy of highly selective endothelin antagonists in partial portal vein ligated (PPVL) rats. METHODS:Four groups...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80303-7
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND & AIMS:Urgency-based allocation that relies on the MELD score prioritizes patients at the highest risk of waitlist mortality. However, identifying patients at greatest risk for short-term post-transplant mortality is needed in order to optimize the potential gains in overall survival obtained through improve...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.03.034
更新日期:2015-09-01 00:00:00
abstract::The EASL Monothematic Conference on Translational Research in Viral Hepatitis brought together a group of leading scientists and clinicians working on both, basic and clinical aspects of viral hepatitis, thereby building bridges from bench to bedside. This report recapitulates the presentations and discussions at the ...
journal_title:Journal of hepatology
pub_type:
doi:10.1016/j.jhep.2014.05.016
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND/AIMS:The aim of this study was to determine the outcome of asymptomatic liver hydatid cysts in a cohort of 33 out of 59 carriers by evaluating clinical and ultrasonographic (US) changes 10-12 years after initial diagnosis. METHODS:We compared US features and cyst size with the original descriptions from 198...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80066-x
更新日期:1999-02-01 00:00:00