scholarly journals Characterization of the inhibition of hepatitis C virus entry byIn vitro-generated and patient-derived oxidized low-density lipoprotein

Hepatology ◽  
2013 ◽  
Vol 57 (5) ◽  
pp. 1716-1724 ◽  
Author(s):  
Sandra Westhaus ◽  
Dorothea Bankwitz ◽  
Stefanie Ernst ◽  
Katrin Rohrmann ◽  
Ilka Wappler ◽  
...  
2002 ◽  
Vol 76 (14) ◽  
pp. 6919-6928 ◽  
Author(s):  
P. André ◽  
F. Komurian-Pradel ◽  
S. Deforges ◽  
M. Perret ◽  
J. L. Berland ◽  
...  

ABSTRACT The presence of hepatitis C virus (HCV) RNA-containing particles in the low-density fractions of plasma has been associated with high infectivity. However, the nature of circulating HCV particles and their association with immunoglobulins or lipoproteins as well as the characterization of cell entry have all been subject to conflicting reports. For a better analysis of HCV RNA-containing particles, we quantified HCV RNA in the low-density fractions of plasma corresponding to the very-low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) fractions from untreated chronically HCV-infected patients. HCV RNA was always found in at least one of these fractions and represented 8 to 95% of the total plasma HCV RNA. Surprisingly, immunoglobulins G and M were also found in the low-density fractions and could be used to purify the HCV RNA-containing particles (lipo-viro-particles [LVP]). Purified LVP were rich in triglycerides; contained at least apolipoprotein B, HCV RNA, and core protein; and appeared as large spherical particles with a diameter of more than 100 nm and with internal structures. Delipidation of these particles resulted in capsid-like structures recognized by anti-HCV core protein antibody. Purified LVP efficiently bind and enter hepatocyte cell lines, while serum or whole-density fractions do not. Binding of these particles was competed out by VLDL and LDL from noninfected donors and was blocked by anti-apolipoprotein B and E antibodies, whereas upregulation of the LDL receptor increased their internalization. These results suggest that the infectivity of LVP is mediated by endogenous proteins rather than by viral components providing a mechanism of escape from the humoral immune response.


2007 ◽  
Vol 194 (1) ◽  
pp. 284
Author(s):  
Soren Nielsen ◽  
Margaret Bassendine ◽  
Dermot Neely ◽  
Siti Ibrahim ◽  
Geoffrey Toms

Hepatology ◽  
2006 ◽  
Vol 43 (5) ◽  
pp. 932-942 ◽  
Author(s):  
Thomas von Hahn ◽  
Brett D. Lindenbach ◽  
Agnès Boullier ◽  
Oswald Quehenberger ◽  
Matthew Paulson ◽  
...  

2011 ◽  
Vol 6 (6) ◽  
pp. 933-945 ◽  
Author(s):  
Sandrine Belouzard ◽  
Laurence Cocquerel ◽  
Jean Dubuisson

AbstractHepatitis C virus (HCV) is a small enveloped virus with a positive stranded RNA genome belonging to the Flaviviridae family. The virion has the unique ability of forming a complex with lipoproteins, which is known as the lipoviroparticle. Lipoprotein components as well as the envelope proteins, E1 and E2, play a key role in virus entry into the hepatocyte. HCV entry is a complex multistep process involving sequential interactions with several cell surface proteins. The virus relies on glycosaminoglycans and possibly the low-density lipoprotein receptors to attach to cells. Furthermore, four specific entry factors are involved in the following steps which lead to virus internalization and fusion in early endosomes. These molecules are the scavenger receptor SRB1, tetraspanin CD81 and two tight junction proteins, Claudin-1 and Occludin. Although they are essential to HCV entry, the precise role of these molecules is not completely understood. Finally, hepatocytes are highly polarized cells and which likely affects the entry process. Our current knowledge on HCV entry is summarized in this review.


2010 ◽  
Vol 84 (22) ◽  
pp. 12048-12057 ◽  
Author(s):  
Takayuki Hishiki ◽  
Yuko Shimizu ◽  
Reiri Tobita ◽  
Kazuo Sugiyama ◽  
Kazuya Ogawa ◽  
...  

ABSTRACT Hepatitis C virus (HCV) is a causative agent of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV in circulating blood associates with lipoproteins such as very low density lipoprotein (VLDL) and low-density lipoprotein (LDL). Although these associations suggest that lipoproteins are important for HCV infectivity, the roles of lipoproteins in HCV production and infectivity are not fully understood. To clarify the roles of lipoprotein in the HCV life cycle, we analyzed the effect of apolipoprotein E (ApoE), a component of lipoprotein, on virus production and infectivity. The production of infectious HCV was significantly reduced by the knockdown of ApoE. When an ApoE mutant that fails to be secreted into the culture medium was used, the amount of infectious HCV in the culture medium was dramatically reduced; the infectious HCV accumulated inside these cells, suggesting that infectious HCV must associate with ApoE prior to virus release. We performed rescue experiments in which ApoE isoforms were ectopically expressed in cells depleted of endogenous ApoE. The ectopic expression of the ApoE2 isoform, which has low affinity for the LDL receptor (LDLR), resulted in poor recovery of infectious HCV, whereas the expression of other isoforms, ApoE3 and ApoE4, rescued the production of infectious virus, raising it to an almost normal level. Furthermore, we found that the infectivity of HCV required both the LDLR and scavenger receptor class B, member I (SR-BI), ligands for ApoE. These findings indicate that ApoE is an essential apolipoprotein for HCV infectivity.


2016 ◽  
Vol 122 (3) ◽  
pp. 287-293 ◽  
Author(s):  
Miyuki Kumano-Kuramochi ◽  
Takashi Fujimura ◽  
Shiro Komba ◽  
Mari Maeda-Yamamoto ◽  
Sachiko Machida

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