[F31] Human retrovirus assembly interplay with the actin cortex

Description

Project Summary/Abstract Human immunodeficiency virus type 1 (HIV-1) is the etiological agent of acquired immunodeficiency syndrome (AIDS). Combined antiretroviral therapy (cART) has resulted from basic research investigation of the HIV life cycle, identifying antiretroviral targets. Virus particle assembly is required for production of infectious virus particles. The Gag structural protein and the genomic RNA (gRNA) are critical structural components required for virus particle assembly. The process of Gag-gRNA targeting to virus particle assembly sites on the plasma membrane remains an important knowledge gap in the field. Targeting of Gag-gRNA to assembly sites requires trafficking through the complex environment of the actin cortex, which is poorly understood. To help address this knowledge gap, this proposal will investigate Gag puncta biogenesis at particle assembly sites and investigate the role of the actin cortex in serving as a physical barrier in human retrovirus particle assembly. A comparative analysis with two closely related human retroviruses, i.e., HIV type 2 (HIV-2) and human T-cell leukemia virus type 1 (HTLV-1), will be done to provide insights into the general nature of the processes under investigation as well as to provide new insights into HIV-1 assembly. Two lines of experimental investigation are proposed. First, experiments will be conducted to learn how changes of cellular gene expression impact the dynamics of actin cortex porosity on virus assembly. These experiments will test the hypothesis that changes in T-cell gene expression upon viral infection increases cortical actin porosity and enhances the efficiency of virus assembly. Second, experiments to assess the relationship between viral genome length on actin cortex partitioning of Gag- gRNA complexes will be done to test the hypothesis that the partition coefficient increases as gRNA length decreases. The identification of the transition midpoint, i.e., where the Gag-gRNA size matches the mesh size of the actin cortex, will be determined and will provide evidence of the threshold for where virus particle assembly is perturbed by cortical actin. The completion of these studies will help address how virus particle assembly sites are located and formed on the plasma membrane and provide new insights into the interrelationship between the actin cortex and the establishment of virus particle assembly sites. Istituzione: UNIVERSITY OF MINNESOTA PI: Gloria Baxter Progetto: 1F31AI197980-01

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Source: reporter.nih.gov