Hepatitis B virus inhibits the expression of complement C3 and C4, in�vitro and in�vivo

Abstract

Abstract. The immune system serves an important function in Hepatitis B virus (HBV) infection, and the complement system is a major component of innate immunity. However, the regulatory effect of HBV on complement proteins has not yet been fully elucidated. The present study focused on investigating the impact of HBV on the expression of complement proteins C3 and C4. A total of 226 patients with a clinical diagnosis of HBV infection were enrolled in the study, including 153 with chronic hepatitis B (CHB) and 73 with hepatocellular carcinoma (HCC), whereas 116 healthy individuals were included as a control group. Immunoturbidimetric detection was performed to determine the levels of complement C3 and C4 in the serum of the patients with HBV and the control group. The results revealed that the mean ± standard deviation C3 and C4 content was 1.223±0.237 and 0.226±0.052 g/l for the control group, 0.687±0.150 and 0.145±0.070 g/l for the patients with CHB, and 0.829±0.332 and 0.174±0.088 g/l for the patients with HCC, respectively. The levels of complement C3 and C4 in the patients with CHB or HCC were significantly lower than the control group (P<0.05). The HBV infectious clone pHBV1.3 was used to transfect Huh7 cells; Huh7 cells transfected with the pBlue-ks empty vector were used as the blank control. The changes in mRNA and protein expression of complements C3 and C4 were detected by RT-PCR and western blotting. When compared with the control cells, the Huh7 cells transfected with pHBV1.3 exhibited reduced C3 and C4 mRNA and protein expression levels. It was concluded that HBV can inhibit the expression of complement C3 and C4 in vitro and in vivo, which may lay the foundation for revealing the pathogenesis of HBV. IntroductionHepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family with an enveloped nucleocapsid containing a partially double-stranded relaxed circular DNA of ~3.2 kb in length with four partially overlapping open-reading frames (S/PreS, C/PreC, P and X) that encode for the viral proteins (1). HBV infection can cause acute and chronic infection, which may ultimately lead to cirrhosis and hepatocellular carcinoma (HCC) (2-4). Worldwide, more than two billion people are infected with HBV, of which 350 million are chronic HBV carriers. Chronic HBV infection is a major risk factor for liver disease, including liver cancer. The total number of people dying from liver fibrosis and HCC caused by HBV each year has reached one million (5,6).The mechanisms involved in the progression and development of HBV-related HCC are not fully understood. Currently, the pathogenicity of HBV is not considered to be attributable to the direct killing of liver cells; instead, it is attributed to the immune dysfunction that occurs subsequent to HBV infection (7). The complement system consists of a group of globulins with enzymatic activity and no heat tolerance; the most important components of the complement system are C3 and C4. As part of the body's innate immune system, these components are involve...

Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients

“…Besides, multivariate Cox regression analysis also showed that C3 levels are an independent predictor of mortality of HBV‐ACLF patients 31 . Similarly, Zhu et al also found that levels of C3 and C4 of CHB patients were significantly lower than those of healthy controls and Huh7 cells transfected with pHBV1.3 displayed lower C3 and C4 expression 32 . Gai et al reported that serum levels of C3 and C4 were significantly higher in patients with HBV‑related compensated cirrhosis compared to decompensated cirrhosis and treatment with entecavir could increase C3 and C4 expression 33 .…”

Association between splenectomy and portal hypertension in the development of pulmonary hypertension

“…Liver function impairment would not only lead to the decreased expression of C3 and C4, 16 but also result in lower synthesis of anti-coagulation factors, including plasma protein C, protein S, and antithrombin-III. Furthermore, splenectomy itself would lead to a loss of splenic filtering function and result in the accumulation of abnormal erythrocytes in circulation, thus potentially exposing phosphatidylserine on cell surfaces and activating coagulation.…”

Plasma proteome plus site‐specific N‐glycoprofiling for hepatobiliary carcinomas

“…Cleaved complement C3 triggers activation of the complement cascade, which augments host immune functions including lysis of bacteria and cells by forming membrane‐attack complex, opsonization, and chemotaxis of leukocytes . It is not surprising that downregulation of complement C3 was detected in patients with HCC because of their compromised immune system during hepatocarcinogenesis. However, beyond empirical speculation, we found that the level of complement C3 correlated positively with poor differentiation of tumor cells and an unfavorable prognosis of HCC.…”