Study On The Biological Traits And Function Of Cytidine Deaminase APOBEC3G

It is widely accepted that carcinogenesis undergoes a series of sequential events which involved with a collection of exterior and internal factors. The environmental etiology of cancer includes chemical, physical and pathogenic factors. The molecular mechanisms of pathogenic factors especially viral ones have become one of the hottest fields in the etiology of cancer. It was shown that over 15-20% cases of cancer have been closely related with viral infection, such as cervix cancer and HPV infection, HCC and HBV, Human T-cell leukemia and HTLV-I, Kaposi and HIV, et al.With the further study on the etiology of cancer, prevention should be most powerful weapon against cancer. The intervention and management of HBV/HIV may prevent or delay the progression of chronic hepatitis B or AIDS, thus will reduce the incidence of cancers related with HBV/HIV infection.Human APOBEC3G (apolipoprotein B-editing catalytic polypeptide 3G) belongs to the cytidine deaminase superfamily. Recently, it was identified as a host factor that inhibits the replication of retroviruses as HIV, SIV, murine leukemia virus (MLV) and hepatitis B virus (HBV). This important finding may lead to complete understanding of the mechanism of human viral infection and provide basis for efficient prevention or clinical treatment of viral infection.During the replication of HIV, AP0BEC3G induces excessive cytosines (C) to uracils (U) deamination of the newly synthesized viral minus-strand DNA which leads to the abortion of viral infection. To counteract the antiviral activity of APOBEC3G, HIV-encoded protein vif mediates APOBEC3G ubiquitination and proteasome-dependent degradation. Since the ability of viral suppression of APOBEC3G is dose-dependent, high expression level of APOBEC3G may also contribute to certain degree of viral suppression in the presence of vif. Therefore, the interactions between viral proteins and AP0BEC3G might be a crucial determinant of HIV susceptibility, viral mutation and the outcome of viral infection. Either inducement of APOBEC3G expression level or blockage of the counteraction function of vif may provide efficient intervention and treatment of HIV infection. However, there were few reports on the expression and regulation of APOBEC3G.HBV replication has also been inhibited by APOBEC3G independent of its deamination activity. It was shown that APOBEC3G and HBcAg may form a complex, thus HBV pregenomic RNA (pgRNA) were prevented to packaged into virion and severed as replication templates. Recently, two groups have demonstrated that AP0BEC3G can inhibit HBV replication in cotransfection system. However, whether it can also inhibit viral replication in a stable HBV-producing cell culture has never been reported.Apart from its antiviral function, the physiological or pathological function and mechanism of AP0BEC3G have not been reported. However, over-expression of APOBEC1 and AID in human and transgene animals was associated with carcinogenesis. Since APOBEC3G can also function as cytidine deaminase and its structure is highly similar to APOBEC1 and AID, whether its over- expression can leads to genomic instability and carcinogenesis should be further investigated.CD4+T cells are the key factor of the body's immune system. During HIV infection, the CD4+T cells are infected and destroyed by the virus. In this way, the body's immune system is significantly weakened from the moment of infection and the inability of the immune system to fight against other virus infection (HSV-8 and EBV, et al.) will opens the door to the malignant tumors such as Kaposi sarcoma and HumanT-cell leukemia, et al. The most important role of hepatitis B virus (HBV) infection in causing HCC is well established. Several lines of evidence point to this strong association. The frequency of HCC correlates with over 80%of chronic HBV infection. The risk of developing HCC was 300 times higher among people who had chronic HBV infection as compared to those without chronic HBV infection. Low efficacy, undesirable side-effects and the occurrence of resistant HIV/ H...