Insilico discovering of STRA6 as a Novel Binding Receptor of Human Immunodeficiency (HIV)

The progressive loss of CD4+ T cell population and thymic dysfunction is the hallmark of HIV-1 (human immunodeficiency virus-1) infection but the mechanism underlying the slow T cell decline and thymic involution remains elusive. Although the chemokine receptor CCR5 (cysteine-cysteine chemokine receptor 5) is the predominant co-receptor exploited for transmission and replication of HIV in vivo but the previous mechanism described via CCR5, based on single-receptor tropism, was insufficient to elucidate the thymic dysfunction and progressive loss of CD4+ T cells caused by HIV infection. It has been demonstrated that acute HIV infection causes retinoic acid (RA) levels to drop quickly and immune cell populations, whose identities and functions are largely regulated by RA. Through this study, we predicted and discovered human STRA6 as a novel binding receptor of HIV that may play a critical role in the pathogenicity of HIV and its immune suppression. Binding between human STRA6 (signaling receptor and transporter of retinol 6) receptor and HIV glycoprotein 120 (GP120) was studied through molecular docking and molecular dynamics simulation analysis. The results showed that the HIV surface glycoprotein (GP120) binds strongly and efficiently to the chain B of the STRA6 receptor at proximity to the RBP (retinol binding protein)- binding motif located in the receptor(ZDOCK score: 1924). From the MD simulation analysis, the binding energies were determined using MM/GBSA (Molecular mechanics with generalised Born and surface area solvation) and was found to be -841.2 kcal/mol signifying a high stability of the complex. It might be possible that HIV infects the thymus gland by binding of the surface glycoprotein (GP120) to the chain B of the membrane STRA6 receptor- a receptor of retinol /Vitamin A (VitA)- which is highly expressed on thymic gland and T cells, leading to retinol signaling disorder or retinol insufficiency which may lead to thymus gland damage and thymic dysfunction resulting in low CD4+ T cells in HIV patients. This study paves the way towards understanding the complex mechanism of HIV infection and its immune dysregulation and may lead to the discovery of new drug targets for management of HIV. More research is needed to fully understand the link between STRA6 receptor and HIV, and it is possible that future studies using animal models, including genetically modified animals, will provide further insights into the mechanisms by which STRA6 receptor play a role in HIV pathogenesis and progression.