Lipoprotein lipase mediates hepatitis C virus (HCV) cell entry and inhibits HCV infection

2007 ◽  
Vol 9 (10) ◽  
pp. 2445-2456 ◽  
Author(s):  
Ursula Andréo ◽  
Patrick Maillard ◽  
Olga Kalinina ◽  
Marine Walic ◽  
Eliane Meurs ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Lipoprotein Lipase ◽  
Hcv Infection ◽  
Cell Entry

scholarly journals Lipoprotein Lipase Inhibits Hepatitis C Virus (HCV) Infection by Blocking Virus Cell Entry

PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e26637 ◽  
Author(s):  
Patrick Maillard ◽  
Marine Walic ◽  
Philip Meuleman ◽  
Farzin Roohvand ◽  
Thierry Huby ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Lipoprotein Lipase ◽  
Hcv Infection ◽  
Cell Entry

scholarly journals Diverse Hepatitis C Virus Glycoproteins Mediate Viral Infection in a CD81-Dependent Manner

2004 ◽  
Vol 78 (16) ◽  
pp. 8496-8505 ◽  
Author(s):  
J. A. McKeating ◽  
L. Q. Zhang ◽  
C. Logvinoff ◽  
M. Flint ◽  
J. Zhang ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepg2 Cells ◽  
Current Model ◽  
Critical Role ◽  
Hcv Infection ◽  
Lymphoid Cells ◽  
Cell Entry ◽  
Virus Infectivity ◽  
Dependent Manner

ABSTRACT We recently reported that retroviral pseudotypes bearing the hepatitis C virus (HCV) strain H and Con1 glycoproteins, genotype 1a and 1b, respectively, require CD81 as a coreceptor for virus-cell entry and infection. Soluble truncated E2 cloned from a number of diverse HCV genotypes fail to interact with CD81, suggesting that viruses of diverse origin may utilize different receptors and display altered cell tropism. We have used the pseudotyping system to study the tropism of viruses bearing diverse HCV glycoproteins. Viruses bearing these glycoproteins showed a 150-fold range in infectivity for hepatoma cells and failed to infect lymphoid cells. The level of glycoprotein incorporation into particles varied considerably between strains, generally reflecting the E2 expression level within transfected cells. However, differences in glycoprotein incorporation were not associated with virus infectivity, suggesting that infectivity is not limited by the absolute level of glycoprotein. All HCV pseudotypes failed to infect HepG2 cells and yet infected the same cells after transduction to express human CD81, confirming the critical role of CD81 in HCV infection. Interestingly, these HCV pseudotypes differed in their ability to infect HepG2 cells expressing a panel of CD81 variants, suggesting subtle differences in the interaction of CD81 residues with diverse viral glycoproteins. Our current model of HCV infection suggests that CD81, together with additional unknown liver specific receptor(s), mediate the virus-cell entry process.

scholarly journals Determinants in the Ig Variable Domain of Human HAVCR1 (TIM-1) Are Required To Enhance Hepatitis C Virus Entry

2018 ◽  
Vol 92 (6) ◽  
pp. e01742-17 ◽  
Author(s):  
Alla Kachko ◽  
Maria Isabel Costafreda ◽  
Iryna Zubkova ◽  
Jerome Jacques ◽  
Kazuyo Takeda ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Hcv Infection ◽  
Cell Entry ◽  
Cellular Receptor ◽  
Phospholipid Binding ◽  
Human Hepatitis ◽  
Binding Function

ABSTRACTHepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. Several host molecules participate in HCV cell entry, but this process remains unclear. The complete unraveling of the HCV entry process is important to further understand viral pathogenesis and develop therapeutics. Human hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, functions as a phospholipid receptor involved in cell entry of several enveloped viruses. Here, we studied the role of HAVCR1 in HCV infection. HAVCR1 antibody inhibited entry in a dose-dependent manner. HAVCR1 soluble constructs neutralized HCV, which did not require the HAVCR1 mucinlike region and was abrogated by a mutation of N to A at position 94 (N94A) in the Ig variable (IgV) domain phospholipid-binding pocket, indicating a direct interaction of the HAVCR1 IgV domain with HCV virions. However, knockout of HAVCR1 in Huh7 cells reduced but did not prevent HCV growth. Interestingly, the mouse HAVCR1 ortholog, also a phospholipid receptor, did not enhance infection and a soluble form failed to neutralize HCV, although replacement of the mouse IgV domain with the human HAVCR1 IgV domain restored the enhancement of HCV infection. Mutations in the cytoplasmic tail revealed that direct HAVCR1 signaling is not required to enhance HCV infection. Our data show that the phospholipid-binding function and other determinant(s) in the IgV domain of human HAVCR1 enhance HCV infection. Although the exact mechanism is not known, it is possible that HAVCR1 facilitates entry by stabilizing or enhancing attachment, leading to direct interactions with specific receptors, such as CD81.IMPORTANCEHepatitis C virus (HCV) enters cells through a multifaceted process. We identified the human hepatitis A virus cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, as a facilitator of HCV entry. Antibody blocking and silencing or knockout of HAVCR1 in hepatoma cells reduced HCV entry. Our findings that the interaction of HAVCR1 with HCV early during infection enhances entry but is not required for infection support the hypothesis that HAVCR1 facilitates entry by stabilizing or enhancing virus binding to the cell surface membrane and allowing the correct virus-receptor positioning for interaction with the main HCV receptors. Furthermore, our data show that in addition to the phospholipid-binding function of HAVCR1, the enhancement of HCV infection involves other determinants in the IgV domain of HAVCR1. These findings expand the repertoire of molecules that HCV uses for cell entry, adding to the already complex mechanism of HCV infection and pathogenesis.

Position Paper on Treatment of Hepatitis C in Romania, 2017. Part One

2017 ◽  
Vol 26 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranţa Iacob ◽  
Roxana Şirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Limit Of Detection ◽  
Position Paper ◽  
Hcv Infection ◽  
Fixed Dose ◽  
Diagnostic Tools ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the first of the two parts of our Society’s recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.Abbreviations: DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESLD: End-stage liver disease; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; EASL: European Association for the Study of the Liver; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: Fixed-dose combination; GT: Genotype; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; LLD: Lower limit of detection; MELD score: Mayo-Clinic End-Stage Liver Disease score; ANMDM: National Agency of Medicines and Medical Devices; PPIs: Proton pump inhibitors; PWID: People who inject drugs; RCT: Randomized controlled trial; RDT: Rapid diagnostic test; RAS: Resistance-associated substitution; SRGH: Romanian Society of Gastroenterology and Hepatology; SAE: serious adverse events; SPC: Summary of Product Characteristics; SVR: Sustained virologic response.

Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two

2017 ◽  
Vol 26 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranța Iacob ◽  
Roxana Șirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Real Life ◽  
Virologic Response ◽  
Position Paper ◽  
Hcv Infection ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the second part of the Society’s recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania. Abbreviations: CKD: Chronic kidney disease; DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESDL: End-stage liver disease; FCH: Fibrosing cholestatic hepatitis; GT: Genotype; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; MELD score: Mayo-Clinic End-Stage Liver Disease score; PDC: Premature discontinuation; PWID: Persons who inject drugs; RASs: Resistance associated substitutions; RBV: Ribavirin; RCT: Randomized controlled trial; SAE: Serious adverse events; SRGH: Romanian Society of Gastroenterology and Hepatology; SVR: Sustained virologic response.

Prevalence and Risk Factors of Hepatitis C Virus (HCV) in Tehsil Batkhela District Malakand, KPK, Pakistan

2018 ◽  
Vol 9 (06) ◽  
pp. 20251-20256
Author(s):  
Mudassir Khan ◽  
Shahrukh Khan ◽  
Shohra Haider ◽  
Fazal Jalil ◽  
Muhsin Jamal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Skin Color ◽  
Significant Risk ◽  
Rapid Test ◽  
Prevalence Ratio ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Common Symptom

Background: Prevalence of Hepatitis C viral infection and its major risk factors has been found out in population of Batkhela, Khyber Pakhtunkhwa, Pakistan by taking number of volunteers from the interested area. HCV prevalence has not been researched in recent time here in this area, so that’s why we contributed. Materials and Methods: Ab rapid test cassette serum/plasma (USA) kit has been used for the mentioned purpose following by ELISA and finally PCR to find out active infection of virus. ICT positive individuals were reconfirmed by ELISA and then ELISA positive samples were carefully investigated by RT-PCR for Hepatitis C Virus. Results: The study population was of 770 volunteers belonging to the mentioned area of research, 453 males and 317 females. The overall prevalence was found to be 5.32% of HCV in Batkhela. This prevalence ratio was 3.12% in males and 2.20 % in females. 3rd generation ELISA was used to refine ICT positive samples which showed that 37 of the ICT positive samples had antibodies detected by ELISA. To find out active HCV infection, ELISA positive samples were refined by real time PCR which showed 2.98% of prevalence of active HCV infection in Batkhela based on HCV RNA in their blood. Principle Conclusion: Overall prevalence was found 5.32%, contaminated reused syringes and blades at Barbour’s shop, blood transfusion, surgical operations and unhygienic food in stalls etc were found significant risk factors for acquiring HCV infection. Body weakness and pale yellow skin color was common symptom in HCV positive volunteers. Safe sexual activities, blood screening before donation and sterilizing surgical equipment’s can protect us from Hepatitis C Virus.

Genetic polymorphisms as the predictors of response to antiviral treatment in chronic hepatitis C virus infection

2011 ◽  
Vol 152 (22) ◽  
pp. 876-881
Author(s):  
Alajos Pár
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Polymorphisms ◽  
Chronic Hepatitis C ◽  
Genome Wide Association Study ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Snp Analysis ◽  
Chronic Hcv

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.

A Serological Storm

1970 ◽  
Vol 9 (2) ◽  
Author(s):  
Bertha Wong MD ◽  
Maria Bagovich MD ◽  
Ivan Blasutig PhD ◽  
Simon Carette MD MPhil
Keyword(s):  
Differential Diagnosis ◽  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Clinical Context ◽  
Autoantibody Profile ◽  
Life Threatening ◽  
Clinically Significant ◽  
Sensory Polyneuropathy

This article describes a patient presenting with a sensory polyneuropathy and multiple autoantibodies, leading to the diagnosis of hepatitis C virus (HCV) infection. His widely positive autoantibody profile in the absence of clinically significant rheumatic disease illustrates the importance of interpreting autoimmune serology in the appropriate clinical context and the concept of HCV being a non-specific activator of the immune system. In addition, it highlights the importance of considering untreated HCV infection in the differential diagnosis of rheumatic complaints, particularly if the workup reveals multiple autoantibodies, as HCV is a potentially severe and life-threatening disease, which can be appropriately managed with effective antiviral therapy.

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