Refereed journal article or data article (A1)

Cytolytic Properties and Genome Analysis of Rigvir® Oncolytic Virotherapy Virus and Other Echovirus 7 Isolates




List of Authors: Hietanen Eero, Koivu Marika A, Susi Petri

Publisher: MDPI

Place: Basel

Publication year: 2022

Journal: Viruses

Volume number: 14

Issue number: 3

DOI: http://dx.doi.org/10.3390/v14030525

URL: https://doi.org/10.3390/v14030525

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/174956199


Abstract

Rigvir® is a cell-adapted, oncolytic virotherapy enterovirus, which derives from an echovirus 7 (E7) isolate. While it is claimed that Rigvir® causes cytolytic infection in several cancer cell lines, there is little molecular evidence for its oncolytic and oncotropic potential. Previously, we genome-sequenced Rigvir® and five echovirus 7 isolates, and those sequences are further analyzed in this paper. A phylogenetic analysis of the full-length data suggested that Rigvir® was most distant from the other E7 isolates used in this study, placing Rigvir® in its own clade at the root of the phylogeny. Rigvir® contained nine unique mutations in the viral capsid proteins VP1-VP4 across the whole data set, with a structural analysis showing six of the mutations concerning residues with surface exposure on the cytoplasmic side of the viral capsid. One of these mutations, E/Q/N162G, was located in the region that forms the contact interface between decay-accelerating factor (DAF) and E7. Rigvir® and five other isolates were also subjected to cell infectivity assays performed on eight different cell lines. The used cell lines contained both cancer and non-cancer cell lines for observing Rigvir®’s claimed properties of being both oncolytic and oncotropic. Infectivity assays showed that Rigvir® had no discernable difference in the viruses’ oncolytic effect when compared to the Wallace prototype or the four other E7 isolates. Rigvir® was also seen infecting non-cancer cell lines, bringing its claimed effect of being oncotropic into question. Thus, we conclude that Rigvir®’s claim of being an effective treatment against multiple different cancers is not warranted under the evidence presented here. Bioinformatic analyses do not reveal a clear mechanism that could elucidate Rigvir®’s function at a molecular level, and cell infectivity tests do not show a discernable difference in either the oncolytic or oncotropic effect between Rigvir® and other clinical E7 isolates used in the study.


Downloadable publication

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.




Last updated on 2022-20-05 at 15:05