Grant: Operating Grant - PA: Bridge Funding -CHVI Vaccine Discovery and Social Research

APOBEC3G (A3G), a deoxycytidine deaminase, is a powerful host antiviral factor that is able to restrict HIV infection by causing virus hypermutations. Moreover, A3G was also shown to act as an inducer of the adaptive immune response. However, during a wild type HIV infection, the antiviral and immunological actions of A3G are counteracted by HIV Vif protein since it induces A3G degradation and blocks A3G virus incorporation. Hence, how to reactivate the antiviral effect of A3G during HIV infection is of considerable interest, as it will provides a basis to develop a novel therapeutic strategy to block HIV infection. Our research group has studied the mechanism of anti-HIV action of A3G and found that by fusing A3G to a HIV-targeting polypeptide (R88), the R88-A3G could change pathway to target into virus and regain anti-HIV activity even in the presence of HIV Vif. Our study clearly showed that when R88-A3G was introduced into human primary PBMCs and macrophages, a significant inhibition of HIV infection was observed. Furthermore, our recent data has demonstrated that R88-A3G was able to target HIV latently infected cells and block the infection and dissemination of different HIV, including drug resistant viruses. All of these data provide the proof of concept for a new anti-HIV strategy based on a natural antiviral molecule. In the proposed study, we will continue our effort to investigate whether introducing R88-A3G into humanized mice is able to restrict HIV infection and meanwhile to spontaneously induce an effective immune response against subsequent HIV challenge. We believe that the fully characterization of this system will lead to develop this approach as new prevention and therapeutic strategy against HIV infection.