Physiological Role of APOBEC3

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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.