Physiological Role of APOBEC3

APOBEC3G是一种胞苷脱氨酶，在病毒组装期间被封装在Δvif HIV-1病毒粒子中，并在病毒感染后阻断其复制。小鼠同源物也对HIV有活性。APOBEC3家族成员的进化早于HIV，最近的研究结果表明，它们可能是阻断体细胞或生殖细胞中内源性遗传元件有害转位的一种手段。也有可能APOBEC3在免疫系统中发挥着额外的作用，要么与它作为DNA突变体的作用有关，要么可能作为RNA编辑器。APOBEC3基因受到严格的转录控制，表征其表达可能为其功能提供线索。我建议用敲除小鼠来研究APOBEC3的生理作用。该研究将揭示APOBEC3G的生理作用，并将为开发针对APOBEC3G的抗病毒治疗提供重要信息。本研究的目的是：1。确定APOBEC3是否调控淋巴细胞的发育、分化和活化，以及敲除小鼠是否存在免疫应答缺陷。2. 确定APOBEC3缺失小鼠的反转录转座子转位是否增加。3. 利用小鼠MusD和IAP反转位模型确定APOBEC3对反转位频率的影响。

APOBEC3G is a cytidine deaminase that is encapsidated in Δvif HIV-1 virions during virus assembly and blocks its replication after viral infection. The mouse ortholog is also active against HIV. APOBEC3 family members evolved prior to HIV and recent findings suggest that they may have been a means of blocking the deleterious transposition of endogenous genetic elements in somatic or germ cells. It is also possible that APOBEC3 plays additional roles in the immune system, either related to its role as a DNA mutator or potentially as an RNA editor. The APOBEC3 gene is under tight transcriptional control and characterization of its expression may provide clues as to its function. I propose to study the physiological role of APOBEC3 using knock-out mice. The study will shed light on the physiological role of APOBEC3G and will provide important information that will help to develop antiviral therapeutics targeting APOBEC3G. The aims of the study are: 1. Determine whether APOBEC3 regulates lymphocyte development, differentiation and activation and whether the knock-out mice have immune response defects. 2. Determine whether retrotransposon transposition is increased in APOBEC3 null mice. 3. Determine the effect of APOBEC3 on retrotransposition frequency using a mouse model for MusD and IAP retrotransposition.