Konstantoulas Constantine James, Hagen Benedikt, Indik Stanislav
Institute of Virology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
J Gen Virol. 2017 Sep;98(9):2362-2367. doi: 10.1099/jgv.0.000897. Epub 2017 Aug 18.
Infectivity of the mouse mammary tumour virus (MMTV) is inhibited by mouse APOBEC3 (mA3) which is efficiently packaged into virions. As the inhibition is only partial, the virus can replicate in tissues expressing mA3 and complete its replication cycle. Here, we have examined the sensitivity of MMTV to inhibition by a human orthologue of mA3, A3G. We report that the virus containing A3G is only moderately susceptible to inhibition by the human factor. Whereas the vif-deficient HIV-1 vector produced in human epithelial cells expressing endogenous levels of A3G was efficiently inhibited, an MMTV vector remained fully infectious. Greater A3G expression levels were necessary to restrict infectivity of MMTV, but only when the factor retained its deaminase activity. Furthermore, the spreading kinetic of a replication competent MMTV was only moderately accelerated in cells with downmodulated A3G expression. These data suggest that MMTV has evolved a mechanism to neutralize antiviral activity of APOBEC3 proteins.
小鼠乳腺肿瘤病毒（MMTV）的感染性受到小鼠载脂蛋白B mRNA编辑酶催化多肽样蛋白3（mA3）的抑制，mA3能有效地包装到病毒粒子中。由于这种抑制只是部分性的，该病毒能够在表达mA3的组织中复制并完成其复制周期。在此，我们研究了MMTV对其人类同源物A3G抑制作用的敏感性。我们报告称，含有A3G的病毒仅对人类因子的抑制作用有中度敏感性。在表达内源性水平A3G的人上皮细胞中产生的vif缺陷型HIV-1载体被有效抑制，而MMTV载体仍具有完全的感染性。需要更高的A3G表达水平来限制MMTV的感染性，但只有当该因子保留其脱氨酶活性时才会如此。此外，在A3G表达下调的细胞中，具有复制能力的MMTV的传播动力学仅被适度加速。这些数据表明，MMTV已经进化出一种机制来中和载脂蛋白B mRNA编辑酶催化多肽样蛋白3（APOBEC3）蛋白的抗病毒活性。
