Effects of the U3 Modulatory Region on Gene Expression from the HIV-1 LTR

Human immunodeficiency virus-1 (HIV-1) generates enormous genetic variability due to its rapid rate of evolution, allowing the virus to quickly adapt to and circumvent the immune systems of infected individuals. This variability has resulted in the rise of nine distinct HIV-1 subtypes and multiple recombinant strains, posing significant challenges to the development of effective therapeutics and vaccines against HIV-1. The initiation of viral gene expression and viral genome replication is governed by the activity of the viral 5’ long terminal repeat (5’LTR). Transcriptional activity from the 5’LTR determines gene expression and ultimately viral replication rates. Significant differences in viral replication rates are observed between subtypes and may be attributed to the subtype-specific conservation of transcription factor binding site (TFBS) architecture on the viral 5’LTR. We describe a system to explore the differences resulting from subtype-specific TFBS architecture conservation and effects on viral replication and gene expression.