Benjamas Aiamkitsumrit Microbiology and Immunology Graduate Program B.S. - Biology, Kasetsart University, Bangkok, Thailand M.S. - Microbiology, Mahidol University, Bangkok, Thailand Email: benjamas.aiamkitsumrit@drexel.edu Advisor: Dr. Brian Wigdahl

Thesis Research Summary:

At the end of 2007, over 30 million people are currently living with human immunodeficiency virus type 1 (HIV-1). HIV-1 disease progression is associated with host immune system deterioration as a consequence of chronic viral replication in susceptible host cells. The failure of the host immune response to clear the virus is partly due to the extraordinary degree of genetic diversity of HIV-1 and complexity of its envelope glycoprotein (Env). The HIV-1 long terminal repeat (LTR) regulates viral gene expression by interaction with viral and cellular proteins including members of the CCAAT/enhancer binding protein (C/EBP) and the Sp transcription factor families. Previous studies in the laboratory have identified the 3T configuration of C/EBP site I (C-to-T change at nucleotide position 3) and 5T configuration of Sp site III (C-to-T change at nucleotide position 5) to correlate with peripheral blood (PB) disease progression and HIV-associated dementia (HAD). The 3T/5T-containing LTR may be representative of an LTR genotype that is preferentially retained, because of specific functional properties involved in disease pathogenesis, in the PB, CNS, and perhaps other compartments as HIV-1-associated disease severity increases suggesting that it may be useful as a predictive viral marker. Microglial cells and perivascular macrophages support most productive HIV-1 replication within the brain, although both have low CD4 levels making macrophage tropism and preferential CCR5 utilization features of CNS-derived viruses/envelopes. Sequence analysis has demonstrated both viral evolution within the CNS and compartmentalization of sequences between brain and peripheral tissues, suggesting the potential for adaptation to replication in the brain environment. In addition, we propose certain envelope sequences are co-selected with this LTR, which play a key role in cell types infected within the peripheral blood and brain. Specifically, my project is to study the specific configuration of HIV-1 LTR transcription factor binding sites in association with certain envelope genotypes in our HIV/AIDS patient cohort. This research is aimed to elucidate the specific viral genetic signatures associated with HIV disease progression and neuropathogenesis.