Cytolytic Properties and Genome Analysis of Rigvir® Oncolytic Virotherapy Virus and Other Echovirus 7 Isolates
In: 14; Viruses; URN:NBN:fi-fe2022081154000; (2022)
Online
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Zugriff:
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.
Titel: |
Cytolytic Properties and Genome Analysis of Rigvir® Oncolytic Virotherapy Virus and Other Echovirus 7 Isolates
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Autor/in / Beteiligte Person: | Koivu Marika, A ; Petri, Susi ; Eero, Hietanen ; biolääketieteen laitos, yhteiset, Institute of Biomedicine ; Turun biotiedekeskus , Turku Bioscience Centre ; 2607100 |
Link: | |
Quelle: | 14; Viruses; URN:NBN:fi-fe2022081154000; (2022) |
Veröffentlichung: | MDPI ; Switzerland ; Sveitsi ; CH ; Basel, 2022 |
Medientyp: | unknown |
ISSN: | 1999-4915 (print) |
DOI: | 10.3390/v14030525 |
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