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.
Effect of garlic (Allium sativum) on lipid profiles, antioxidant activity and expression of scavenger receptor class B type I (SR-BI) in liver and intestine of hypercholesterolemic mice
