Vpu protein

PDB 1pje EBI

Vpu protein is a viral protein unique to the Human Immunodeficiency Virus (HIV), specifically found in HIV-1. The name Vpu stands for Viral Protein U, where "U" refers to its unique nature. This protein plays a crucial role in the virus's life cycle, particularly in the release of new virus particles from infected cells and the degradation of CD4 molecules.

Function

The primary functions of Vpu are to facilitate the release of new virions from the host cell and to degrade the CD4 molecules on the surface of infected cells. CD4 is the primary receptor for HIV entry into cells, and its degradation is believed to prevent superinfection, where a cell is infected by more than one virus particle, and to enhance the release of new virus particles.

Virus Release

Vpu enhances the release of newly formed HIV-1 particles from the cell membrane of the host cell. It achieves this by antagonizing a host cell protein called tetherin (also known as BST-2), which normally prevents the release of the virus from the cell surface. By downregulating tetherin, Vpu promotes the efficient detachment and release of HIV-1 particles.

CD4 Degradation

Vpu induces the degradation of CD4 molecules in the endoplasmic reticulum. This prevents the newly formed HIV-1 particles from binding to CD4 molecules on the surface of the infected cell, which could inhibit their release and infectivity. The degradation of CD4 also reduces the likelihood of the immune system recognizing and attacking the infected cell.

Structure

Vpu is a small, integral membrane protein composed of two major domains: a transmembrane domain that anchors it in the membrane and a cytoplasmic domain that interacts with various cellular and viral proteins. The structure of Vpu allows it to interact with the cellular machinery involved in protein degradation and export.

Clinical Significance

Understanding the function and structure of Vpu has significant implications for HIV research and treatment. Inhibiting Vpu's function could be a potential strategy for antiretroviral therapy, as it would hinder the virus's ability to spread and destroy the immune system. Research into Vpu inhibitors is ongoing, with the goal of finding new treatments for HIV/AIDS.

See Also

• HIV/AIDS
• Antiretroviral therapy
• Viral life cycle
• Protein degradation

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