Human Immunodeficiency Virus type 1 (HIV-1) targets CD4+ cells, weakening the immune system and potentially leading to AIDS. Understanding the virus's structure and focusing on its more stable regions is essential to create more effective treatments. Genomic recognition, a highly conserved process, represents a promising drug target. Mutagenesis studies have identified the Core Encapsidation Signal (CES) as the minimal packaging unit for HIV-1, which shows nucleocapsid (NC) binding. Ding et al. determined the highest affinity binding sites of NC on the 5’ Leader of HIV are in the CES region. The central finding was that the binding of NC causes unwinding within the PSI hairpin of the viral RNA, which is important for genome packaging and viral replication. Our project focuses on the MAL over Ding's NL4-3 strain of HIV-1 to determine the binding characteristics of NC on the RNA packing signal. To quantify the number of binding sites in the MAL packaging signal and the affinity of NC on those sites, we utilized Nuclear Magnetic Resonance and Isothermal Calorimetry. Our next goal will be to characterize the RNA and Gag interactions important for nucleocapsid binding, genome selection, and selective packaging. Overall, understanding the conserved region advances HIV antiviral therapies.
