Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee 37208, USA.
J Virol. 2011 May;85(9):4510-9. doi: 10.1128/JVI.01925-10. Epub 2011 Feb 23.
APOBEC3G, a potent HIV-1 host restriction factor, is overcome by HIV-1 viral infectivity factor (Vif), which induces its polyubiquitination and proteasomal degradation. Here we show that lysine-deficient APOBEC3G with an N-terminal hemagglutinin (HA) tag fusion (HA-A3G20K/R) was resistant to HIV-1 Vif-induced proteasomal degradation. HA-A3G20K/R molecules were packaged into wild-type HIV-1 particles, and HA-A3G20K/R drastically decreased wild-type HIV-1 reverse transcription products and infectivity. We also showed that the N terminus of A3G was a target of polyubiquitination induced by HIV-1 Vif. Thus, fusion of the HA tag to the N terminus of A3G20K/R reduced its polyubiquitination, the likely mechanism for the resistance of this protein to HIV-1 Vif-induced proteasomal degradation. Finding such ways to induce resistance of A3G to Vif may provide new approaches to anti-HIV/AIDS therapy.
APOBEC3G 是一种有效的 HIV-1 宿主限制因子，但其易被 HIV-1 病毒感染力因子（Vif）所克服，后者诱导其多聚泛素化和蛋白酶体降解。在此，我们发现带有 N 端血凝素（HA）标签融合（HA-A3G20K/R）的赖氨酸缺陷型 APOBEC3G 对 HIV-1 Vif 诱导的蛋白酶体降解具有抗性。HA-A3G20K/R 分子被包装到野生型 HIV-1 颗粒中，HA-A3G20K/R 极大地减少了野生型 HIV-1 逆转录产物和感染性。我们还表明，A3G 的 N 端是 HIV-1 Vif 诱导的多聚泛素化的靶标。因此，HA 标签与 A3G20K/R 的 N 端融合降低了其多聚泛素化，这可能是该蛋白对 HIV-1 Vif 诱导的蛋白酶体降解产生抗性的机制。寻找这种诱导 A3G 对 Vif 产生抗性的方法可能为抗 HIV/AIDS 治疗提供新途径。
