Investigation of HIV‐1 Protein‐Lipid Interactions During Assembly at the Plasma Membrane

Abstract

Human immunodeficiency virus (HIV‐1) is an enveloped retrovirus that infects T‐helper lymphocytes and leads to acquired immune deficiency syndrome (AIDS) through destruction of this crucial arm of the human immune system. HIV‐1 replicates through virion assembly and budding at the plasma membrane of T‐helper lymphocytes, leading to virus proliferation and lymphocyte depletion. Several virus‐encoded proteins direct this process, including the p17 matrix domain (MA). This 17‐kDa protein binds to the plasma membrane and is essential for membrane localization, assembly, and budding of nascent virions. Recent structural, computational, and cell studies have provided insight into how HIV‐1 MA is targeted to the plasma membrane. This study supplements previous research by providing biophysical data on the membrane binding properties of MA. We demonstrate the lipid affinity, specificity, and membrane penetration of MA in addition to showing how phosphorylation events may mediate membrane targeting. Together, these data help elucidate the mechanism of MA targeting to the plasma membrane and the role matrix‐lipid interactions play in the assembly and budding of HIV‐1 virions. Further examination of matrix‐membrane interactions will provide a greater understanding of the role of lipids in the viral life cycle and of their potential as targets for exciting and novel therapeutic strategies.