The N-terminal Of EIAV Rev Is Essential For Gag Assembly And Responsible For Neutralizing EqA3Z3

In recent years, some intracellular molecules were discovered in research of retrovirus, including Trim5a, Tetherin, SAMHDI and APOBEC3etc. that act as innate immune barrieres for viral infection and are named natural restriction factors. These restriction factors inhibit viral replication through different mechanism. For instance, TRIM5a can damage the synthesis of viral DNA and restrict the viral uncoating; Tetherin blocks the release of enveloped virus from the cell surface; SAMHDI inhibits viral replication through influencing materials of viral DNA synthesis; APOBEC3influences viral replication by super-mutating on virus cDNA. In contrast, virus evolves special mechanisms for antagonizing natural restrictions. Research on the mechanism of interaction between virus and restrction factors is vital for uncovering the lentiviral infection mechanism and developing antiviral drugs.Equine infectious anemia virus (EIAV) belongs to lentivirus and infects equine, is also one of the important lentiviral models. In terms of equine innate immunity, several equine restrction factors were gradually dicovered and were demonstrated could inhibit EIAV replication. This study focused on the mechanism of interaction between a novel equine APOBEC3mutant and EIAV. Firstly, five equine APOBEC3genes were identified, and a new A3Z3haplotype (eqA3Z3V2) that contains three mutants was also identified in equine samples. In addition, equine APOBEC3eukaryotic expression vectors were constructed. Then the activities of these equine APOBEC3were evaluated through EIAV reporter system, the result showed eqA3Z3,-V1and-V2reduced EIAV-luc infectivity approximately10fold which was a similar result as a previous report. Notably, eqA3Z3V2could reduce Gag processing by inhibiting the truncated Rev function, which resulted in reducing viral production, and the58site of eqA3Z3V2protein was demonstrated the vital amino acid. In contrast, EIAV used wild type to antagonize the activity of eqA3Z3V2. Finally, we suggested a new viewpoint that nuclear export pathway could regulate EIAV Gag assembly features, and built a model of interaction between Rev/RRE, Gag and eqA3Z3.This study firstly help to explain the interaction mechanism between equine A3s and EIAV; Secondly they help to clarify the function of Rev protein in viral mature process and understand pathogenic characteristics of EIAV. In addition, as one of important lentiviral animal models, illuminating molecular interaction mechanism of EIAV protein and host protein will provide important reference for prevention and control strategy of lentiviral infection.