Bag2 Is a Component of a Cytosolic Extraction Machinery That Promotes Membrane Penetration of a Nonenveloped Virus

Journal of Virology
Allison Dupzyk, Billy Tsai

Abstract

During entry, the nonenveloped polyomavirus (PyV) simian virus 40 (SV40) traffics from the cell surface to the endoplasmic reticulum (ER), where it penetrates the ER membrane to reach the cytosol; the virus is then transported into the nucleus to cause infection. Although a coherent understanding of SV40's host entry is emerging, how the virus is ejected from the ER into the cytosol remains mysterious. Our previous analyses revealed that the cytosolic Hsc70-SGTA-Hsp105 complex binds to SV40 and extracts it from the ER into the cytosol. We now report that the nucleotide exchange factor (NEF) Bag2 stimulates SV40 release from Hsc70, thereby enabling successful virus arrival at the cytosol, which leads to infection. Hsp105, another NEF of Hsc70, displays a function overlapping that of Bag2, underscoring the importance of this release reaction. Our findings identify a new component of an extraction machinery essential during membrane penetration of a nonenveloped virus and provide further mechanistic insights into this process.IMPORTANCE How a nonenveloped virus penetrates a biological membrane to cause infection is a mystery. For the nonenveloped polyomavirus SV40, transport across the ER membrane to reach the cytosol is an essent...Continue Reading

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Citations

Jan 23, 2020·Viruses·Lenka HorníkováJitka Forstová
Mar 13, 2019·Cold Spring Harbor Perspectives in Biology·Ranen Aviner, Judith Frydman
Mar 13, 2020·Journal of Virology·Xiaofang Liu, Billy Tsai
Apr 8, 2020·The Journal of Cell Biology·Chelsey C SpriggsBilly Tsai
Aug 28, 2020·Frontiers in Microbiology·Zeng WangJianke Wang
Mar 11, 2021·Current Opinion in Virology·Colleen L MayberryMelissa S Maginnis
Jun 3, 2021·Viruses·Kaitlyn SpeckhartBilly Tsai

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