Chiu Ya-Lin, Greene Warner C
Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA.
Annu Rev Immunol. 2008;26:317-53. doi: 10.1146/annurev.immunol.26.021607.090350.
All retroviruses, including HIV-1, display species-specific patterns of infection. The impaired growth of these retroviruses in foreign and sometimes even in their natural hosts often stems from the action of potent host-encoded "viral restriction factors" that form important protective components of the innate immune system. The discovery of APOBEC3G and related cytidine deaminases as one class of host restriction factors and of the action of HIV-1 Vif as a specific APOBEC3G antagonist have stimulated intense scientific interest. This Vif-APOBEC3G axis now forms a very attractive target for development of an entirely new class of anti-HIV drugs. In this review, we summarize current understanding of the mechanism of action of the APOBEC3 family of enzymes, their intriguing regulation within cells, the impact of these enzymes on viral evolution and disease progression, and their roles in controlling not only the replication of exogenous retroviruses but also the retrotransposition of endogenous retroelements.
所有逆转录病毒,包括HIV-1,都表现出物种特异性的感染模式。这些逆转录病毒在异种宿主甚至有时在其自然宿主中的生长受损,通常源于强大的宿主编码“病毒限制因子”的作用,这些因子构成了先天免疫系统的重要保护成分。APOBEC3G和相关胞苷脱氨酶作为一类宿主限制因子的发现,以及HIV-1 Vif作为特定APOBEC3G拮抗剂的作用,激发了强烈的科学兴趣。这种Vif-APOBEC3G轴现在成为开发全新一类抗HIV药物的极具吸引力的靶点。在本综述中,我们总结了目前对APOBEC3家族酶作用机制的理解、它们在细胞内有趣的调控、这些酶对病毒进化和疾病进展的影响,以及它们在不仅控制外源性逆转录病毒复制而且控制内源性逆转元件逆转座方面的作用。