scholarly journals A Human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo

Hepatology ◽  
2011 ◽  
Vol 55 (2) ◽  
pp. 364-372 ◽  
Author(s):  
Philip Meuleman ◽  
Maria Teresa Catanese ◽  
Lieven Verhoye ◽  
Isabelle Desombere ◽  
Ali Farhoudi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Scavenger Receptor ◽  
Type I ◽  
Hepatitis C Virus Infection ◽  
Viral Spread ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Scavenger Receptor Class B Type I and Hepatitis C Virus Infection of Primary Tupaia Hepatocytes

2005 ◽  
Vol 79 (9) ◽  
pp. 5774-5785 ◽  
Author(s):  
Heidi Barth ◽  
Raffaele Cerino ◽  
Mirko Arcuri ◽  
Marco Hoffmann ◽  
Peter Schürmann ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Surface ◽  
Scavenger Receptor ◽  
Hcv Infection ◽  
Type I ◽  
Scavenger Receptor Class ◽  
Class B

ABSTRACT Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. The study of early steps during HCV infection has been hampered by the lack of suitable in vitro or in vivo models. Primary Tupaia hepatocytes (PTH) have been shown to be susceptible to HCV infection in vitro and in vivo. Human scavenger receptor class B type I (SR-BI) represents an HCV receptor candidate mediating the cellular binding of E2 glycoprotein to HepG2 hepatoma cells. However, the function of SR-BI for viral infection of hepatocytes is unknown. In this study, we used PTH to assess the functional role of SR-BI as a putative HCV receptor. Sequence analysis of cloned tupaia SR-BI revealed a high homology between tupaia and human SR-BI. Transfection of CHO cells with human or tupaia SR-BI but not mouse SR-BI cDNA resulted in cellular E2 binding, suggesting that E2-binding domains between human and tupaia SR-BI are highly conserved. Preincubation of PTH with anti-SR-BI antibodies resulted in marked inhibition of E2 or HCV-like particle binding. However, anti-SR-BI antibodies were not able to block HCV infection of PTH. In conclusion, our results demonstrate that SR-BI represents an important cell surface molecule for the binding of the HCV envelope to hepatocytes and suggest that other or additional cell surface molecules are required for the initiation of HCV infection. Furthermore, the structural and functional similarities between human and tupaia SR-BI indicate that PTH represent a useful model system to characterize the molecular interaction of the HCV envelope and SR-BI on primary hepatocytes.

scholarly journals p21-activated Kinase-1 (PAK1) Inhibition of the Human Scavenger Receptor Class B, Type I Promoter in Macrophages Is Independent of PAK1 Kinase Activity, but Requires the GTPase-binding Domain

2001 ◽  
Vol 276 (50) ◽  
pp. 46807-46814 ◽  
Author(s):  
Thomas G. Hullinger ◽  
Robert L. Panek ◽  
Xiangyang Xu ◽  
Sotirios K. Karathanasis
Keyword(s):  
High Density Lipoprotein ◽  
Promoter Activity ◽  
Kinase Activity ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Type I ◽  
Down Regulation ◽  
Scavenger Receptor Class ◽  
Class B

Scavenger receptor class B, type I (SR-BI), is a high density lipoprotein receptor that mediates the flux of cholesterol between high density lipoprotein and cells. Recent evidence suggests that SR-BI plays a role in atherosclerosis and that inflammatory mediators down-regulate SR-BI in the macrophage. The purpose of this study was to evaluate the ability of lipopolysaccharide (LPS) to down-regulate the activity of the human SR-BI promoter in the macrophage and to delineate the mechanisms involved. Experiments with cultured cells andin vivoderived macrophages showed that LPS has a powerful suppressive effect on SR-BI expression bothin vitroandin vivo. Transient transfection studies demonstrated that LPS represses SR-BI promoter activity in the macrophage cell line RAW 264.7. Cotransfection with either a constitutively active p21-activated protein kinase-1 (PAK1) construct (T423E) or a kinase-deficient PAK1 construct (K299R) resulted in repression of the SR-BI promoter, similar to LPS. These results demonstrate that PAK1-mediated down-regulation of the SR-BI promoter is independent of PAK1 kinase activity and suggest that PAK1 mediates the LPS-induced decrease in promoter activity. Cotransfection with constitutively active Cdc42 or Rac expression constructs also resulted in down-regulation of the promoter; whereas the dominant-negative Cdc42 and Rac constructs elevated basal promoter activity and blunted the LPS response. Cotransfection of PAK1 constructs containing mutations in both the kinase domain and the Cdc42/Rac-binding domain attenuated the PAK1-mediated down-regulation of the promoter, suggesting that Rac and Cdc42 are required for PAK1-mediated decreases in SR-BI promoter activity. 5′-Deletion analysis and gel shift data suggest that LPS inhibits binding of a novel transcription factor to a myeloid zing finger protein-1-like element (−476 to −456) in the human SR-BI promoter. These results demonstrate that the PAK1 pathway down-regulates the SR-BI promoter and suggest that activation of this pathway may play an important role in cholesterol trafficking in the vessel wall.

scholarly journals Scavenger Receptor Class B Type I Is More Conducive to Hepatitis C Virus Invasion Compared with Low-Density Lipoprotein Receptor

2020 ◽  
Author(s):  
Xiangyi Cao ◽  
Qiong Kang ◽  
Deng Jiang ◽  
Jun Xiao ◽  
Yanyu Zhang ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Type I ◽  
Lipoprotein Receptor ◽  
Scavenger Receptor Class ◽  
Recombinant Cells ◽  
Class B ◽  
Density Lipoprotein Receptor

Abstract Background: Hepatitis C virus is the major cause of chronic hepatitis which may deteriorate into liver cirrhosis or hepatocellular carcinoma. A number of studies have demonstrated that HCV cell entry is a complex multi-step process involving several cellular proteins, such as scavenger receptor class B type I (SR-BI), tetraspanin CD81, tight junction protein claudin-1 (CLDN-1) and occludin (OCLN). The low-density lipoprotein receptor (LDLR) is an important factor during the initial HCV particle-binding step, which interacts with the complex formed between the virus particle and the lipoprotein in the blood. However, the process of HCV early infection is not well-established, with many details remaining to be elucidated.This research aimed to study the early entry stage of HCV virus particles and the role of LDLR more effectively.Methods: Recombinant murine cell models of HCV infection in vitro was constructed, that expressed human HCV receptors, such as LDLR, CD81, SR BI, CLDN-1, and OCLN. These factors were also introduced to mice by hydrodynamic delivery to construct a humanized mouse model of HCV infection in vivo.Expression levels of the mRNA of HCV entry factors in recombinant cells were measured by qRT-PCR.Western blotting was used to determine whether the recombinant cells successfully expressed cellular proteins. HCV RNA was assayed by q-PCR following the incublation of HCVsd and HCVcc with the transgenice.Results: Transgenic murine cell lines and mice were developed successfully, and expressed four or five human HCV entry factors in tandem or individually, respectively. We found that all of these transgenic cells and mice were susceptible to HCV, and five entry factors (5EF) rendered higher infectivity. Additionally, we observed that four entry factors (4EF/hLDLR-) could facilitate abundant HCV entry, but four other factors (4EF/hSR-BI-) were less effective.Conclusions: Whether in vitro or in vivo, SR-BI is an essential factor in HCV invasion, and target cells and mice were more vulnerable to the virus in the presence of SR-BI than LDLR. These results suggested that SR-BI may be a potential drug target to inhibit HCV early infection, and the absence of LDLR could reduce the infectivity to the virus.

scholarly journals The postbinding activity of scavenger receptor class B type I mediates initiation of hepatitis C virus infection and viral dissemination

Hepatology ◽  
2012 ◽  
Vol 57 (2) ◽  
pp. 492-504 ◽  
Author(s):  
Muhammad N. Zahid ◽  
Marine Turek ◽  
Fei Xiao ◽  
Viet Loan Dao Thi ◽  
Maryse Guérin ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Scavenger Receptor ◽  
Type I ◽  
Hepatitis C Virus Infection ◽  
Viral Dissemination ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Respective contributions of intestinal Niemann-Pick C1-like 1 and scavenger receptor class B type I to cholesterol and tocopherol uptake: in vivov. in vitro studies

2011 ◽  
Vol 107 (9) ◽  
pp. 1296-1304 ◽  
Author(s):  
Emmanuelle Reboul ◽  
Zeina Soayfane ◽  
Aurélie Goncalves ◽  
Michela Cantiello ◽  
Romain Bott ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Scavenger Receptor ◽  
Special Focus ◽  
Type I ◽  
Cholesterol Uptake ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Niemann Pick ◽  
Distal Jejunum

The intestinal absorption of cholesterol and lipid micronutrients such as vitamin E has been shown to share some common pathways. The present study aims to further compare the uptake of cholesterol ([3H]cholesterol v. 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3-ol (NBD-cholesterol)) and tocopherol in Caco-2 TC-7 cells and in mouse intestine, with special focus on the respective roles of scavenger receptor class B type I (SR-BI) and Niemann-Pick C1-like 1 (NPC1L1). Conversely to NBD-cholesterol, the uptakes of [3H]cholesterol and tocopherol by Caco-2 cells were impaired by both block lipid transport-1 and ezetimibe, which inhibit SR-BI and NPC1L1, respectively. These inhibitions occurred only when cholesterol or tocopherol was delivered to cells included in micelles that contained biliary acid and at least oleic acid as a lipid. In vivo, after 2 h of digestion in mice, the uptake of the two cholesterol analogues and of tocopherol all showed distinct patterns along the duodenum–jejunum axis. [3H]Cholesterol uptake, which correlated closely to NPC1L1 mRNA expression in wild-type (wt) mice, was strongly inhibited by ezetimibe. Intestinal SR-BI overexpression did not change NPC1L1 expression and led to a significant increase in [3H]cholesterol uptake in the distal jejunum. Conversely, neither ezetimibe treatment nor SR-BI overexpression had an effect on NBD-cholesterol uptake. However, in contrast with SR-BI mRNA expression, tocopherol absorption increased strongly up to the distal jejunum in wt mice where it was specifically inhibited by ezetimibe, and was increased in the proximal intestine of intestinal SR-BI-overexpressing mice. Thus, cholesterol and tocopherol uptakes share common pathways in cell culture models, but display different in vivo absorption patterns associated with distinct contributions of SR-BI and NPC1L1.

scholarly journals In vitro and in vivo studies of nanoparticles of chitosan-Pandanus tectorius fruit extract as new alternative treatment for hypercholesterolemia via Scavenger Receptor Class B type 1 pathway

2020 ◽  
Vol 28 (10) ◽  
pp. 1263-1275
Author(s):  
Efriyana Oksal ◽  
Inten Pangestika ◽  
Tengku Sifzizul Tengku Muhammad ◽  
Habsah Mohamad ◽  
Hermansyah Amir ◽  
...  
Keyword(s):  
Alternative Treatment ◽  
Scavenger Receptor ◽  
In Vivo Studies ◽  
Fruit Extract ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Pandanus Tectorius

scholarly journals Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81

Hepatology ◽  
2007 ◽  
Vol 46 (6) ◽  
pp. 1722-1731 ◽  
Author(s):  
Mirjam B. Zeisel ◽  
George Koutsoudakis ◽  
Eva K. Schnober ◽  
Anita Haberstroh ◽  
Hubert E. Blum ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Scavenger Receptor ◽  
Host Factor ◽  
Type I ◽  
Hepatitis C Virus Infection ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Successful anti-scavenger receptor class B type I (SR-BI) monoclonal antibody therapy in humanized mice after challenge with HCV variants within vitroresistance to SR-BI-targeting agents

Hepatology ◽  
2014 ◽  
Vol 60 (5) ◽  
pp. 1508-1518 ◽  
Author(s):  
Koen Vercauteren ◽  
Naomi Van Den Eede ◽  
Ahmed Atef Mesalam ◽  
Sandrine Belouzard ◽  
Maria Teresa Catanese ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Scavenger Receptor ◽  
Antibody Therapy ◽  
Humanized Mice ◽  
Type I ◽  
Monoclonal Antibody Therapy ◽  
Scavenger Receptor Class ◽  
Class B
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