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Elucidating HIV-1 capsid interactions with host cofactors


EMSL Project ID
51381

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection is a global epidemic. Between the point of entry into the cell and integration of the HIV-1 genome into the host genome, the virus encounters many host cofactors, primarily interacting with the viral capsid that houses the viral genome. These host cofactors can work to inhibit or promote viral infection. For example, TrimCyp inhibits viral infection, BICD2 shuttles the capsid towards the nucleus, and CPSF6 ensures proper integration of the viral genome into the host genome. Here, we propose to solve high-resolution structures of these host cofactors complexed with HIV-1 capsid constructs using single particle cryo-EM reconstruction. High resolution structures of these complexes will elucidate the mechanisms of actions for each of these host-viral interactions, providing insight into how HIV-1 infection is inhibited, how HIV-1 is shuttled through the cell, and how the HIV-1 capsid genome is incorporated into the host genome.

Project Details

Start Date
2020-05-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Yong Xiong
Institution
Yale University

Team Members

Chunxiang Wu
Institution
Yale University

Shuai Yuan
Institution
Yale University

Therese Tripler
Institution
Yale University

Janette Myers
Institution
Oregon Health & Science University

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory