A Very Late Viral Protein Triggers the Lytic Release of SV40

Robert Daniels,Dorota Sadowicz,Daniel N Hebert,Thomas J Hope

doi:10.1371/journal.ppat.0030098

Abstract

How nonenveloped viruses such as simian virus 40 (SV40) trigger the lytic release of their progeny is poorly understood. Here, we demonstrate that SV40 expresses a novel later protein termed VP4 that triggers the timely lytic release of its progeny. Like VP3, VP4 synthesis initiates from a downstream AUG start codon within the VP2 transcript and localizes to the nucleus. However, VP4 expression occurs ∼24 h later at a time that coincides with cell lysis, and it is not incorporated into mature virions. Mutation of the VP4 initiation codon from the SV40 genome delayed lysis by 2 d and reduced infectious particle release. Furthermore, the co-expression of VP4 and VP3, but not their individual expression, recapitulated cell lysis in bacteria. Thus, SV40 regulates its life cycle by the later temporal expression of VP4, which results in cell lysis and enables the 50-nm virus to exit the cell. This study also demonstrates how viruses can generate multiple proteins with diverse functions and localizations from a single reading frame.

Highlights

Eukaryotic cells use a range of mechanisms and pathways to shuttle molecules across their complex endomembrane network [1]
While these data are supportive of VP2 and VP3 potentially playing a role in the lytic release of simian virus 40 (SV40), it remains to be determined if other viral or host cellular proteins are involved in this process
Lysis has been thought to be a nonspecific consequence of viral protein overexpression and the massive production of viral progeny

Summary

Introduction

Eukaryotic cells use a range of mechanisms and pathways to shuttle molecules across their complex endomembrane network [1] Viruses exploit these pathways to gain entry into the cell and navigate through the various membrane barriers [2,3]. Nonenveloped viruses, including simian virus 40 (SV40), initiate their release from the host cell in a lytic manner. In SV40, the core structural proteins VP2 and VP3 are capable of permeabilizing bacterial membranes and post-translationally integrating into ER membranes in a VP1-regulated manner [7,8] While these data are supportive of VP2 and VP3 potentially playing a role in the lytic release of SV40, it remains to be determined if other viral or host cellular proteins are involved in this process

Methods

Results

Discussion

Conclusion