BST-2 Inhibits IAV Infection And Studies On The Mechanism Of APOBEC3G And Vif Based On Structural Prediction

Viruses are easy to obtain the drug resistance due to high mutation rate. The novel antiviral agents targeting host restriction factors could reduce the development of drug resistance. Therefore the interaction of host restriction factors with viral proteins has become a hot spot of research. The drive force of the research is in-depth knowledge of interaction between host restriction factors and viral proteins. In the two sections of this study, we studied the interactions between BST-2 and Influenza A Virus M2, APOBEC3G and Vif, respectively.In the first section, we investigated the effects of BST-2 on replication of Influenza A Virus. BST-2 is a host restriction factor which localized at lipid rafts of cell membrane, and is active against divers families of enveloped virus. BST-2 could inhibits Influenza A Virus release since Influenza A Virus utilizes lipid rafts as a budding site. In this work, we examined the effect of BST-2 on Influenza A Virus releasing. We found that BST-2 inhibited the releasing of Influenza A Virus. BST-2 down-regulated M2 expression in vivo, suggesting that BST-2 may inhibits the budding of IVA by impairing the function of Influenza A Virus M2. Further study revealed that BST-2 may down-regulate M2 in ubiquitin-independent degradation pathway. We also studied the effect of bovine-BST-2 on Influenza A Virus release. Our results showed that bovine-BST-2, just like human-BST-2, inhibited the budding of IVA by affecting the biological function of Influenza A Virus M2.The second section we studied the interaction between APOBEC3G and Vif. We utilized homology modeling and comparative modeling constructed full-length APOBEC3G and Vif models for the first time. We also constructed APOBEC3G-dimer and APOBEC3G-Vif complex models based on these two models. We found that 124-127 amino acid residues of APOBEC3G involve in both of APOBEC3G dimer-formation and its interaction with Vif. Our results showed that Vif interrupted APOBEC3G dimer formation in vivo suggesting that the substrate of APOBEC3G degrades by Vif could be monomer. Further results revealed that APOBEC3G through N-terminal to accomplish the dimer formation and interaction with Vif. Single amino acid residues substitutions on APOBEC3G 124-127 altered the subcellular location of APOBEC3G, and reduced dimer formation. But these APOBEC3G mutants were not resistant to Vif degradation, and were able to interact with Vif. All these results indicated that APOBEC3G dimer formation and interaction with Vif may involve in multiple amino acid residues work together, and different domains of APOBEC3G may involve in the interaction with Vif and degradation by Vif.