CBF-β辅助SIVagm Vif蛋白诱导限制因子APOBEC3G的降解

CBF-β required for SIVagm Vif-mediated A3G degradation

APOBEC3蛋白家族是一类重要的慢病毒复制的免疫限制因子。慢病毒编码的附属蛋白Vif可以与Cullin5-Elongin B/Elongin C形成E3泛素化连接酶复合物使APOBEC3G(A3G)聚泛素化和降解,从而抑制A3G对病毒的限制。CBF-β为RUNX家族转录辅助因子,可以调节Vif介导的A3G降解作用。为探索CBF-β对非洲绿猴免疫缺陷病毒Vif蛋白(SIVagm Vif)的调节机制以及对A3G降解的影响,本研究通过生化及病毒学方法对SIVagm和HIV-1编码的Vif蛋白与CBF-β作用进行了对比性研究。结果显示,SIVagm编码的Vif对A3G的降解同样需要CBF-β的辅助。当Vif(HIV-1/SIVagm)编码的第38位色氨酸突变成丝氨酸后,CBF-β辅助Vif调节A3G降解的功能显著降低。由此表明,第38位色氨酸对于不同慢病毒编码的Vif与CBF-β的相互作用具有重要作用。由此推测,CBF-β辅助Vif介导的降解A3G的作用在灵长类慢病毒中具有保守性。

APOBEC3 proteins family is an important inhibitors for diverse lentivirus. Lentivirus Vif is able to promote the poly ubiquitination and degrade APOBEC3 substrates by recruiting E3 ubiquitin ligase complex with CUL5-Elongin B/C-based. In some lentivirus, CBF-β was identified as an exclusive cofactor for Vif-mediated degradation of A3G for HIV-1. To investigate the underlying mechanism of CBF-β which was shown as molecule chaperon to Vif of other primate lentivirus, we systematically compare the effects on degradation of A3G in vitro between HIV-1 and SIVagm by biochemical and virological methods. Here we confirmed that CBF-β is also required for SIVagm Vif-mediated degradation African Green Monkey A3G, indicating functional conservation. In addition, the 38th tryptophan of Vif （HIV-1/SIVagm） is important for Vif-binding to CBF-β, which mutated to serine reducing Vif-mediated degradation of A3G. Our results provided essential basis to further study on the interaction of CBF-β and Vif and might be very valuable on designing of novel anti-primate lentivirus drugs.