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

Chen Chen,Liu Liu,Tsai Tsai

doi:10.3390/v11100917

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.

Highlights

A virus must traverse through the elaborate inter-connected endomembrane system of the host cell, reaching an intracellular organelle where it escapes into the cytosol via penetration of a cellular membrane
In the case of the nonenveloped human papillomavirus (HPV), the endosome-localized HPV is sorted to the Golgi apparatus where it remains hidden until mitosis
The only other virus reported to be trafficked to the endoplasmic reticulum (ER) is the HPV [80], it is unclear whether transit to the ER represents the productive pathway for this virus

Summary

Introduction

A virus must traverse through the elaborate inter-connected endomembrane system of the host cell, reaching an intracellular organelle where it escapes into the cytosol via penetration of a cellular membrane. Viral disassembly is coupled to different entry steps to ensure eventual delivery of the virus to the replication site. Because a nonenveloped virus lacks a surrounding membrane, a structural protein on the surface of the virus is responsible for this interaction This binding event triggers receptor-mediated endocytosis, trafficking the virus to the endosomes. Rather than sorting to the lysosomes, a virus may penetrate the endosome membrane, thereby escaping into the cytosol and the nucleus to trigger infection—this productive route most aptly describes the fate of the nonenveloped adenovirus [7]. SV40 binds to a host cell receptor at the plasma membrane, initiating receptor-mediated endocytosis that targets SV40 to the endosomes (Figure 1B, step 1). Transcription and replication of the viral genome lead to lytic infection or cellular transformation

Receptor-Mediated Endocytosis to Endosomes

Targeting to the Endoplasmic Reticulum

ER Membrane Penetration to Enable Viral Escape into the Cytosol

Nuclear entry

Conclusions and Future Directions