Does the Evidence Support the Existence of the Simian Polyomavirus SV40 Vp4 Viroporin?

Stian Henriksen,Christine Hanssen Rinaldo

doi:10.1128/msphere.00019-20

Stian Henriksen, Christine Hanssen Rinaldo

Open Access

https://doi.org/10.1128/msphere.00019-20

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Abstract

The simian polyomavirus SV40 was reported to express Vp4, an N-terminally truncated form of the minor capsid proteins Vp2 and Vp3. Since a missense mutation of the putative Vp4 start codon (Vp2M228I) was found to give reduced progeny release and delayed lysis, Vp4 was claimed to be a viroporin. However, two independent research groups, including our own, were unable to replicate these findings. In contrast, we found no Vp4 expression in SV40-infected cells and no reduction in progeny release for Vp4-deficient virus, and finally, we found that the single amino acid substitution unavoidably introduced into the overlapping Vp2/Vp3 genes during Vp4 mutagenesis reduced early steps but not virus release. Remarkably, the existence of the viroporin Vp4 still seems to be widely accepted, which presumably is preventing important research on polyomavirus release. With this perspective, we will review and comment on the most important experiments that led to the disputed announcement of the viroporin Vp4.

Highlights

The simian polyomavirus simian virus 40 (SV40) was reported to express Vp4, an N-terminally truncated form of the minor capsid proteins Vp2 and Vp3
We review the key experiments that led Daniels and colleagues [3] to conclude that Vp4 is a late protein that triggers the lytic release of SV40 and comment on why these data, in our view, do not constitute sufficient evidence of Vp4 expression and viroporin activity
SV40 Vp4 may be expressed in the artificial setting of translation in rabbit reticulocyte extracts or after transfection with an SV40 genome without upstream start codons

Summary

Introduction

The simian polyomavirus SV40 was reported to express Vp4, an N-terminally truncated form of the minor capsid proteins Vp2 and Vp3. SV40 Vp4deficient mutants show the same infectivity as wild-type virus, except when an isoleucine is introduced, perturbing the function of the minor capsid proteins Vp2/Vp3 in entry. Neither the in vitro translation nor the translation start codon prediction is sufficient evidence for Vp4 expression in SV40-infected cells.

Results

Conclusion