Up-regulation of interferon-a/APOBEC3G signal pathway potently inactivates HIV-1 infectivity in resting CD4-T cells

Background: Interferon (IFN) system, including various IFNsand IFN-inducible gene products, is well known for its potentinnate immunity against wide-range viruses. Recently, a family ofcytidine deaminases, functioning as another innate immunityagainst retroviral infection, has been identified. However, itsregulation remains largely unknown.Methods: IFN-a was added to the culture of resting CD4 Tcells.The expression of APOBEC3G was detected with realtime RT-PCR and Western blotting. The promoter of APOBEC3Gwas analyzed by luciferase expression. The effect ofIFN-a/APOBEC3G upon HIV-1 was examined by treating thecells with APOBEC3G-specific siRNA.Results: We have demonstrated that, through a regular IFN-asignal transduction pathway, IFN-a can significantly enhance theexpression of APOBEC3G in human primary resting but notactivated CD4 T-cells, and the amounts of APOBEC3Gassociated with a low molecular mass (LMM). Interestingly,short-time treatments of newly-infected resting CD4 T-cellswith IFN-a will significantly inactivate human immunodeficiencyvirus type 1 (HIV-1) at its early stage. This inhibition can becounteracted by APOBEC3G-specific short interfering RNA(siRNA), indicating that IFN-a-induced APOBEC3G plays a keyrole to mediate this anti-HIV-1 process. Conclusion: Our data suggest that APOBEC3G is also amember of IFN system, at least in the resting CD4 T-cells. Giventhat IFN-a/APOBEC3G pathway has potent anti-HIV-1 capabilityin resting CD4 T-cells, augmentation of this innate immunitybarrier could prevent residual HIV-1 replication in its nativereservoir in the post-highly active antiretroviral therapy(HAART) era.