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Review
. 2019 Oct 5;11(10):917.
doi: 10.3390/v11100917.

SV40 Hijacks Cellular Transport, Membrane Penetration, and Disassembly Machineries to Promote Infection

Yu-Jie Chen  1 , Xiaofang Liu  2 , Billy Tsai  3
Affiliations
Review

SV40 Hijacks Cellular Transport, Membrane Penetration, and Disassembly Machineries to Promote Infection

Yu-Jie Chen et al. Viruses. .

Abstract

During entry, a virus must be transported through the endomembrane system of the host cell, penetrate a cellular membrane, and undergo capsid disassembly, to reach the cytosol and often the nucleus in order to cause infection. To do so requires the virus to coordinately exploit the action of cellular membrane transport, penetration, and disassembly machineries. How this is accomplished remains enigmatic for many viruses, especially for viruses belonging to the nonenveloped virus family. In this review, we present the current model describing infectious entry of the nonenveloped polyomavirus (PyV) SV40. Insights from SV40 entry are likely to provide strategies to combat PyV-induced diseases, and to illuminate cellular trafficking, membrane transport, and disassembly mechanisms.

Keywords: SV40; endoplasmic reticulum; membrane penetration; nonenveloped virus; viral disassembly.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results

Figures

Figure 1
Figure 1
SV40 structure and entry pathway. (A) Diagram of the SV40 structure. (B) To begin the entry process, SV40 binds to a host cell receptor at the plasma membrane called ganglioside GM1 (step 1). This event initiates receptor-mediated endocytosis that targets the virus to the endosomes. From the endosomes, SV40 is targeted to the ER (step 2) from where it breaches the ER membrane to escape into the cytosol (step 3). Upon reaching the cytosol, the virus is further mobilized into the nucleus (step 4) where its genome is released. Transcription and replication of the viral genome then lead to lytic infection or cellular transformation.
Figure 2
Figure 2
SV40 cell entry via caveolae-dependent endocytosis. The host entry receptor for SV40 is the glycolipid molecule called ganglioside GM1. Receptor-engagement enables caveolae-dependent endocytosis that targets the virus to the endosomes. From the endosomes, the virus is targeted to the ER.
Figure 3
Figure 3
ER-to-cytosol membrane escape of SV40. To initiate ER-to-cytosol membrane escape of SV40, the ER-resident redox proteins PDI, ERp57, and ERdj5 reduce and isomerize the disulfide bonds of the virus (step 1), generating a partially destabilized hydrophobic particle that inserts into the ER membrane. In the ER membrane, EMC1 acts to stabilize the membrane-inserted virus to prevent more pronounced viral disassembly that would preclude entry into the cytosol. To reach the cytosol, SV40 induces the formation of a membrane penetration site called foci (step 2), a structure where select host components including BAP31 and DNA J proteins (B12, B14, and C18) are reorganized. The subsequent recruitment of a cytosol extraction machinery (composed of Hsc70, Hsp105, Bag2, and SGTA) to the J proteins enables the ejection of the ER membrane-inserted SV40 into the cytosol (step 3). Cytosol-localized virus finally enters the nucleus to promote infection.
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