Franca Raffaella, Spadari Silvio, Maga Giovanni
Istituto di Genetica Molecolare IGM-CNR, Pavia, Italy.
Med Sci Monit. 2006 May;12(5):RA92-8.
The APOBEC (acronym for apolipoprotein B editing catalytic polypeptide) family of cytidine deaminases are widely distributed in the biological world and play a central role in diverse enzymatic pathways. Members of this family (APOBEC3G and APOBEC3F) have been recently shown to be able to restrict HIV-1 replication in physiologically relevant target cells (macrophages, lymphocytes), presumably by triggering extensive deamination of the viral RNA/DNA replication intermediates. This natural antiretroviral host defense mechanism is counteracted by the HIV-1 protein Vif, which is able to target APOBECs to degrade. The so-called "Vif/APOBEC3G paradigm" has been confirmed by a growing literature. However, evidence arising from recent studies has expanded this view, showing that the replication of other viruses is also restricted by APOBEC family members and suggesting antiviral mechanism(s) of action unrelated to the catalytic activity of these proteins. Furthermore, evolutionary investigations on primates have shown that APOBEC3 gene expansion might be related to an ancient adaptive selection to prevent endogenous genetic instability, indicating an additional ancient protective role of APOBECs. This article is aimed at broadening the current knowledge about the antiviral activity of the APOBEC members and to highlight the notion that their role(s) might be more general than previously anticipated.
载脂蛋白B编辑催化多肽（APOBEC）家族的胞苷脱氨酶广泛分布于生物界，在多种酶促途径中发挥核心作用。最近研究表明，该家族成员（APOBEC3G和APOBEC3F）能够在生理相关靶细胞（巨噬细胞、淋巴细胞）中限制HIV-1复制，推测是通过引发病毒RNA/DNA复制中间体的广泛脱氨作用。HIV-1蛋白Vif能够靶向APOBECs使其降解，从而抵消这种天然的抗逆转录病毒宿主防御机制。越来越多的文献证实了所谓的“Vif/APOBEC3G范式”。然而，最近研究得出的证据扩展了这一观点，表明其他病毒的复制也受到APOBEC家族成员的限制，并提示了与这些蛋白质催化活性无关的抗病毒作用机制。此外，对灵长类动物的进化研究表明，APOBEC3基因的扩增可能与防止内源性基因不稳定的古老适应性选择有关，这表明APOBECs还具有额外的古老保护作用。本文旨在拓宽当前关于APOBEC家族成员抗病毒活性的认识，并强调其作用可能比之前预期更为广泛的观点。
