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NIH grant 1F31AI197980-01: Human retrovirus assembly interplay with the actin cortex
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Gloria Baxter. Award: $48621.
Start: 2026-10-07T00:00:00.
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.document fetched 2026-10-24 02:46