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Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
Published on: August 21, 2017
A chaperone-activated nonenveloped virus perforates the physiologically relevant endoplasmic reticulum membrane
Emily K Rainey-Barger1, Brian Magnuson, Billy Tsai
1Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Rm. 3043, Ann Arbor, MI 48109, USA.
Journal of Virology
|September 21, 2007
Summary
The endoplasmic reticulum chaperone ERp29 activates polyomavirus (Py) to perforate the ER membrane. Viral protein VP2 mediates this essential membrane penetration step for infection.
Area of Science:
- Virology
- Cell Biology
- Membrane Biology
Background:
- Nonenveloped viruses, like polyomavirus (Py), must penetrate cellular membranes to infect hosts.
- The precise mechanism of endoplasmic reticulum (ER) membrane penetration by Py remains unclear.
- The ER chaperone ERp29 was previously shown to alter Py coat protein VP1 conformation, facilitating membrane interaction.
Purpose of the Study:
- To elucidate the mechanism of ER membrane penetration by polyomavirus.
- To identify the viral components responsible for membrane perforation.
- To link cellular chaperone activity to viral membrane penetration.
Main Methods:
- Development of a membrane perforation assay using physiologically relevant ER membranes.
- Biochemical analysis of viral proteins in activated viral particles.
- Demonstration of viral protein interactions with and integration into the ER membrane.
Main Results:
- ERp29-activated Py successfully perforates the ER membrane.
- The internal viral protein VP2 is exposed upon ERp29 activation.
- VP2 binds to, integrates into, and perforates the ER membrane, while VP3 integrates but does not perforate.
- Cellular factor ERp29's role in activating Py for membrane perforation was confirmed.
Conclusions:
- Viral protein VP2 is the key mediator of ER membrane perforation during polyomavirus infection.
- The interaction between cellular factors and viral proteins is critical for initiating viral entry.
- This study identifies a specific viral component responsible for a crucial step in nonenveloped virus infection.
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