Presentation Title

Characterizing the Role of EWI-2 Palmitoylation During HIV-1 Infection

Abstract

Human Immunodeficiency Virus type 1 (HIV-1) encodes the accessory proteins Nef, Vif, Vpr, and Vpu which alter the host cellular environment to promote virus production and evade immune detection. Vpu downregulates host surface factors including tetraspanins and EWI-2, two known fusion inhibitors. Fusion inhibitory proteins prevent excessive HIV-1-induced cell-cell fusion through their localization at the virological synapse (VS); A cellular junction created when the viral protein Envelope (Env) on the surface of an infected producer cell binds to the CD4 receptor on the surface of an uninfected target cell, allowing for efficient cell-to-cell virus transmission. This reveals the dichotomy of EWI-2 and CD81 in promoting viral spread, as they are downregulated, yet recruited to the VS to prevent cell-cell fusion. Palmitoylation of the EWI-2 cytoplasmic tail is required for interactions with CD81 yet remains relatively unstudied in the context of HIV-1 infection. Given that the EWI-2-CD81 interaction is crucial for their regulatory functions, we hypothesize that palmitoylation is necessary for Vpu-mediated EWI-2 downregulation as well as accumulation at the VS. Flow cytometry and microscopy will be used on cells expressing palmitoylation deficient EWI-2 to analyze their effect on accumulation at the VS and downregulation by Vpu.

Primary Faculty Mentor Name

Markus Thali

Graduate Student Mentors

Emily Whitaker

Status

Graduate

Student College

College of Agriculture and Life Sciences

Program/Major

Microbiology and Molecular Genetics

Primary Research Category

Biological Sciences

Secondary Research Category

Health Sciences

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Characterizing the Role of EWI-2 Palmitoylation During HIV-1 Infection

Human Immunodeficiency Virus type 1 (HIV-1) encodes the accessory proteins Nef, Vif, Vpr, and Vpu which alter the host cellular environment to promote virus production and evade immune detection. Vpu downregulates host surface factors including tetraspanins and EWI-2, two known fusion inhibitors. Fusion inhibitory proteins prevent excessive HIV-1-induced cell-cell fusion through their localization at the virological synapse (VS); A cellular junction created when the viral protein Envelope (Env) on the surface of an infected producer cell binds to the CD4 receptor on the surface of an uninfected target cell, allowing for efficient cell-to-cell virus transmission. This reveals the dichotomy of EWI-2 and CD81 in promoting viral spread, as they are downregulated, yet recruited to the VS to prevent cell-cell fusion. Palmitoylation of the EWI-2 cytoplasmic tail is required for interactions with CD81 yet remains relatively unstudied in the context of HIV-1 infection. Given that the EWI-2-CD81 interaction is crucial for their regulatory functions, we hypothesize that palmitoylation is necessary for Vpu-mediated EWI-2 downregulation as well as accumulation at the VS. Flow cytometry and microscopy will be used on cells expressing palmitoylation deficient EWI-2 to analyze their effect on accumulation at the VS and downregulation by Vpu.