At present, it is generally considered that liver cells damage is not directly associated with CHB pathogenesis, but caused by inflammatory reaction and immune response of the body after HBV infection . Studies showed that HBV infection could regulate the changes of numerous protein expression, including interleukins 27 (IL-27), IL-29, IL-8 and cyclooxygenase (COX-2), etc. [2, 6].
HepG2.2.15 cell line is a kind of hepatoma cell line stably transfected with the HBV genome, and can express viral RNA and protein, synthetise and secrete the complete virus-like particles. To further explore the pathogenesis of CHB, differential expression genes in HepG2.2.15 and HepG2 cells were screened by gene chip, a series of differentially expressed proteins were found, such as ApoA1. A previous research results indicated that HBV inhibited the synthesis and secretion of ApoB by the regulation of microsomal triglyceride transfer protein (MTP) expression .
Gene chip technology has the characteristics of high flux and high sensitivity, but there are certain false positive and false negative at the same time. We confirmed the result of gene chip by RT-PCR and Western-blot. Many studies have shown that the level of circulating ApoA1 correlates with CHB and CHB related disease [3, 8–10]. Our results suggested HBV inhibited the expression of ApoA1 mRNA and protein. Furthermore we detected the serum ApoA1 level in CHB patients and healthy controls. The decrease of serum ApoA1 levels indicated that HBV could inhibit the expression of ApoA1 mRNA and protein in vitro. ApoA1 is the carrier of free cholesterol in vivo, and the major structural protein of HDL-C. The serological level of HDL-C in these two groups was further tested. The serum levels of HDL-C in CHB patients were lower than that in the healthy controls, which demonstrated that HBV affected the serum HDL-C levels by inhibiting the expression of ApoA1.
To explore the molecular mechanism of ApoA1 expression regulated by HBV, we achieved ApoA1 promoter (−474 + 7) by PCR amplification, cloned it to pGL3-basic vector with luciferase reporter gene and constructed ApoA1 promoter luciferase reporter gene pApoA1-Luc . The regulation of HBV on ApoA1 promoter was measured with fluorescent reporter gene system, and the change of ApoA1 mRNA and protein expression was detected by RT-PCR and Western-blot. ApoA1 expression in promoter, mRNA and protein levels, were inhibited by HBV, in a dose-dependent effect. All these indicated that HBV was likely to down regulate the activity of ApoA1 promoter to inhibit ApoA1 mRNA and protein expression. However, the signal pathway of the regulation of HBV on ApoA1 expression and its exact mechanism remained unknown.
A number of studies had shown that viral infections could cause the disorder of lipoprotein metabolism in vivo, such as ApoA1, ApoB, HDL-C, low density lipoprotein cholesterol (LDL-C), total triglyceride (TG) and other apolipoproteins, and lipoprotein levels in serum were reduced after heptatitis C virus (HCV) infection [12–14]. In other studies, an inverse correlation between HBV and ApoA1 was found in two hepatoma cell lines  and plasma ApoA1 was decreased in chronic hepatitis B patients . Consistent with these findings, in our research, we investigated the effect of HBV on ApoA1 expression, and found out that HBV inhibited the synthesis and secretion of ApoA1 and HDL-C at the same time. HBV infection could cause acute or chronic inflammation of the body and studies have confirmed the anti-inflammatory effect of HDL-C . HBV might suppress the synthesis and secretion of HDL-C by inhibiting ApoA1 expression, and then promote the inflammatory response. Information from previous research of HBV effect on ApoB expression and this current research make it clear that HBV infection can also lead to the disorders of lipid metabolism. However, whether HBV infection as well as HCV infection is able to cause liver steatosis remains unclear.