Physiological Role of APOBEC3

APOBEC 3G是一种胞苷脱氨酶，在病毒组装期间在Δvif HIV-1病毒粒子中被糖苷化，并在病毒感染后阻断其复制。小鼠直系同源物也具有抗HIV活性。APOBEC 3家族成员在HIV之前进化，最近的研究结果表明，它们可能是阻止体细胞或生殖细胞中内源性遗传元件有害转座的一种手段。APOBEC 3也可能在免疫系统中发挥其他作用，无论是作为DNA突变体还是潜在的RNA编辑器。APOBEC 3基因处于严格的转录控制之下，其表达的表征可能为其功能提供线索。我建议使用基因敲除小鼠研究APOBEC 3的生理作用。这项研究将揭示APOBEC 3G的生理作用，并将提供重要信息，有助于开发针对APOBEC 3G的抗病毒治疗药物。本研究的目的是：1.确定APOBEC 3是否调节淋巴细胞发育、分化和活化，以及敲除小鼠是否存在免疫应答缺陷。2.确定逆转录转座子转座是否在APOBEC 3敲除小鼠中增加。3.使用MusD和IAP逆转录转座的小鼠模型确定APOBEC 3对逆转录转座频率的影响。

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.