BINDONG LIU, PHD, LAB STARTUP PACKAGE: HIV IN AFRICAN AMERICANS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。载脂蛋白B基因编码酶催化多肽样3G(APOBEC3G)是一种新发现的宿主抗逆转录病毒因子。它属于一个具有胞苷脱氨酶活性的蛋白质家族。通常认为，APOBEC 3G通过在新合成的病毒DNA中诱导致命的G到A超突变来限制HIV-1的复制。还观察到APOBEC3G导致病毒逆转录(RT)、DNA核导入和HIV-1复制过程中多步骤缺陷的整合。在超突变和多步骤缺陷之间仍存在一些重大差距。我们的研究兴趣之一是了解APOBEC 3G如何限制HIV-1复制的细节。越来越多的体外证据表明，APOBEC 3G是一种有效的宿主限制因子，可抑制HIV-1的复制。目前还不确定APOBEC 3G是否也影响艾滋病毒的传播和疾病的进展。据报道，艾滋病毒和艾滋病对非裔美国人的影响不成比例，其比率是美国白人人口的10倍。自1996年以来，非洲裔美国人中发生的艾滋病病例比美国其他任何种族/民族人口都多。最近的一项研究报道，APOBEC 3G外显子4的一个密码子变化变体H186R在非裔美国人中是多态的。对于非裔美国人来说，186R等位基因的变异与CD4T细胞的下降密切相关，186R等位基因也与非裔美国人加速进展为艾滋病定义的疾病有关。了解APOBEC 3G的变异是否会影响艾滋病毒的传播和疾病的进展将是一件有趣的事情。通过对APOBEC 3G基因变异和表达水平的研究，我们将有兴趣了解APOBEC 3G基因变异与HIV在不同种族群体中传播和疾病进展的关系。它将协助确定如何改进或发展针对少数民族人口的新的预防或治疗方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (Apobec3G) is a newly defined host anti-retroviral factor. It belongs to a family of proteins that have cytidine deaminase activity. It is commonly believed that Apobec 3G restricts HIV-1 replication by inducing lethal G to A hypermutations in the newly synthesized viral DNA. It has also been observed that Apobec3G causes viral reverse transcription (RT), DNA nuclear import and integration of multiple steps of defects during HIV-1 replication. There are still some major gaps between the hypermutations and the multiple steps of defects. One of our research interest is to understand the details of how Apobec 3G restricts HIV-1 replication. More and more in vitro evidence suggested that Apobec 3G is a potent host restriction factor against HIV-1 replication. It is still uncertain whether Apobec 3G also influence HIV transmission and disease progression. It has been reported that HIV and AIDS disproportionately affect African Americans at a rate that is 10 times greater than is found in the U.S. White population. Since 1996, more AIDS cases have occurred among African Americans than any other U.S racial/ethnic population. A recent study reported that one codon-changing variant, H186R in exon 4 of Apobec 3G, was polymorphic in African Americans. For African Americans, the variant allele 186R was strongly associated with decline in CD4 T cells, the 186R allele was also associated with accelerated progression to AIDS-defining conditions in African Americans. It would be interesting to know whether the variation of Apobec 3G will influence HIV transmission and disease progression. We will be interested to look at the relationship between the variation of Apobec 3G and HIV transmission and disease progression among different racial group through the study of Apobec 3G genetic variation and expression levels. It will assist in determining how to improve or develop new prevention or therapeutic approaches specific to ethnic minority populations.