Mouse APOBEC3 (mA3) inhibits murine leukemia virus (MuLV) replication by a deamination-independent mechanism in which the reverse transcription is considered the main target process. However, other steps in virus replication that can be targeted by mA3 have not been examined. We have investigated the possible effect of mA3 on MuLV protease-mediated processes and found that mA3 binds both mature viral protease and Pr180gag-pol precursor polyprotein. Using replication-competent MuLVs, we also show that mA3 inhibits the processing of Pr65 Gag precursor. Furthermore, we demonstrate that the autoprocessing of Pr180gag-pol is impeded by mA3, resulting in reduced production of mature viral protease. This reduction appears to link with the above inefficient Pr65gag processing in the presence of mA3. Two major isoforms of mA3, exon 5-containing and -lacking ones, equally exhibit this antiviral activity. Importantly, physiologically expressed levels of mA3 impedes both Pr180gag-pol autocatalysis and Pr65gag processing. This blockade is independent of the deaminase activity and requires the C-terminal region of mA3. These results suggest that the above impairment of Pr180gag-pol autoprocessing may significantly contribute to the deaminase-independent antiretroviral activity exerted by mA3.

中文翻译：

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小鼠APOBEC3干扰鼠白血病病毒Pr180gag-pol前体的自催化裂解，并抑制Pr65gag加工。

小鼠APOBEC3（mA3）通过依赖于脱氨基作用的机制抑制鼠白血病病毒（MuLV）的复制，其中逆转录被认为是主要的靶标过程。但是，尚未检查可被mA3靶向的病毒复制中的其他步骤。我们已经研究了mA3对MuLV蛋白酶介导的过程的可能影响，并发现mA3结合了成熟的病毒蛋白酶和Pr180gag-pol前体多蛋白。使用具有复制能力的MuLV，我们还显示mA3抑制Pr65 Gag前体的加工。此外，我们证明Pr3gag-pol的自动加工受到mA3的阻碍，导致成熟病毒蛋白酶的产量降低。在mA3存在下，这种减少似乎与上述效率低下的Pr65gag处理有关。mA3的两种主要同工型，含5号外显子和5号外显子的外显子同样具有这种抗病毒活性。重要的是，mA3的生理表达水平既阻碍了Pr180gag-pol的自催化作用，又阻碍了Pr65gag的加工。这种阻断作用与脱氨酶活性无关，并且需要mA3的C端区域。这些结果表明，Pr180gag-pol自体加工的上述损伤可能显着促进了mA3产生的不依赖脱氨酶的抗逆转录病毒活性。