Inhibitory Effect Of Hepatitis B Virus Core Antibody IgG On Hepatitis B Virus Replication

Hepatitis B virus (hepatitis B virus, HBV) is one of the most common human viruses that cause persistent infection, within about 2 billion people worldwide have been infected or are infected with hepatitis B virus, of which 240 million chronic hepatitis B HIV, up to the global burden of disease study in 2010 showed that infection with hepatitis B virus resulted in about 78.6 million deaths annually ranked as one of the 10 leading causes of death. Because some countries and regions still do not promote the hepatitis B vaccine immunization and vaccine nonresponse emerging, as well as antiviral drugs are expensive, long-term use can cause serious side effects and drug-resistant strains emerge and other reasons, in addition to population movements worldwide and chronic hepatitis B virus infection progress to cirrhosis and liver cancer in high-risk, making hepatitis B virus infection is still one of the important problems which threaten the health of the world’s population.Hepatitis B virus infection is mainly dependent on the outcome of the interaction between the virus and the immune system, the study of the immune response to hepatitis B virus clearance mechanisms to seek an effective target for treatment of hepatitis B virus infection is very important. In a study of hepatitis B virus found antibodies against the hepatitis B virus core protein is an antibody infection first appeared, almost all of hepatitis B infection will occur in vivo and can be life-long presence in infected individuals. Many on core antibody-positive hepatitis B infection separate study showed that the majority of these patients in the low viral replication or occult infection status. Therefore, we speculate that the persistence of core antibody inhibits the replication of hepatitis B virus replication leads to this low state. In this study, the use of purified human-derived hepatitis B virus core antibody IgG treatment can stably express HBV viral HepG2.2.15 cell, core antibody IgG possible mechanism of inhibition of intracellular HBV replication was discussed. First, we use immunoblotting techniques and pepsin IgG immunoglobulin specific hydrolysis core antibody IgG can prove via FcRn (Fc receptor segment)-mediated into the liver cells. Secondly, the use of laser scanning confocal microscopy and immunoblotting demonstrated that the core IgG antibodies can enter cells and core antigen to form immune complexes and accumulate in the cytoplasm side of the nuclear membrane, thereby affecting core antibody subcellular distribution. As the core protein nucleic acid molecules can be used as nuclear transfer shuttle vector, viral RNA transcription intermediate cccDNA carry into the cytoplasm; another core protein or a combination of important structural protein cccDNA formation of micro-chromosomes, can promote cccDNA molecules by binding to CpG islands HBV replication and transcription. So core antibody IgG molecules into cells combines core antigen is bound to affect its function, thereby inhibiting HBV replication. Third, we use a chemiluminescent microparticle immunoassay, fluorescent quantitative real-time PCR technology and real-time fluorescence quantitative RT-PCR technique to give 96 hours of core antibody-treated cell culture supernatant HepG2.2.15 hepatitis B virus surface antigen, e antigen, HBV DNA closed circular DNA (cccDNA) and pregenomic RNA (pgRNA) the concentration of intracellular HBV covalent and were determined. The results showed that:compared with the control group, the core surface antigen antibody treatment group, e and pgRNA intracellular antigen 72 hours after the appearance significantly decreased, with obvious time and dose dependent. Compared with the control group, the core antibody IgG-treated group when the culture supernatant HBV DNA72 hours increased slightly, a significant decrease in 96 hours. The levels of intracellular HBV cccDNA within 96 hours did not appear to change significantly. The first study found that hepatitis B virus core antibody IgG as a classic addition to hepatitis B virus infection serological markers, but also be able to inhibit the replication of hepatitis B virus in the cell. And preliminary evidence of liver cells into the core antibodies inhibit viral replication mechanisms may play a role by interfering with viral replication in the core protein to achieve. This topic is more comprehensive understanding of the hepatitis B virus and the immune system interactions, and chronic hepatitis B virus infection provides a new perspective.