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

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.