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.
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