Investigating the effect of reduced temperatures on the efficacy of rhabdovirus-based viral vector platforms

Rhabdoviral vectors can induce lysis of cancer cells. While studied almost exclusively at 37 °C, viruses are subject to a range of temperatures in vivo , including temperatures ≤31 °C. Despite potential implications, the effect of temperatures <37 °C on the performance of rhabdoviral vectors is u...

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Published inJournal of general virology Vol. 105; no. 8
Main Authors Kakish, Julia E., Mehrani, Yeganeh, Kodeeswaran, Arthane, Geronimo, Katrina, Clark, Mary Ellen, van Vloten, Jacob P., Karimi, Khalil, Mallard, Bonnie A., Meng, Baozhong, Bridle, Byram W., Knapp, Jason P.
Format Journal Article
LanguageEnglish
Published England Microbiology Society 22.08.2024
Subjects
Animal
Animals
Cell Line
Cell Line, Tumor
Cold Temperature
Genetic Vectors - genetics
Humans
Negative-strand RNA Viruses
Oncolytic Virotherapy - methods
Oncolytic Viruses - genetics
Oncolytic Viruses - physiology
Rhabdoviridae - genetics
Rhabdoviridae - physiology
Temperature
Vesiculovirus - genetics
Vesiculovirus - physiology
Virus Replication
temperature
rhabdovirus
viral vector
oncolytic
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Summary:Rhabdoviral vectors can induce lysis of cancer cells. While studied almost exclusively at 37 °C, viruses are subject to a range of temperatures in vivo , including temperatures ≤31 °C. Despite potential implications, the effect of temperatures <37 °C on the performance of rhabdoviral vectors is unknown. We investigated the effect of low anatomical temperatures on two rhabdoviruses, vesicular stomatitis virus (VSV) and Maraba virus (MG1). Using a metabolic resazurin assay, VSV- and MG1-mediated oncolysis was characterized in a panel of cell lines at 28, 31, 34 and 37 °C. The oncolytic ability of both viruses was hindered at 31 and 28 °C. Cold adaptation of both viruses was attempted as a mitigation strategy. Viruses were serially passaged at decreasing temperatures in an attempt to induce mutations. Unfortunately, the cold-adaptation strategies failed to potentiate the oncolytic activity of the viruses at temperatures <37 °C. Interestingly, we discovered that viral replication was unaffected at low temperatures despite the abrogation of oncolytic activity. In contrast, the proliferation of cancer cells was reduced at low temperatures. Equivalent oncolytic effects could be achieved if cells at low temperatures were treated with viruses for longer times. This suggests that rhabdovirus-mediated oncolysis could be compromised at low temperatures in vivo where therapeutic windows are limited.
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These authors share senior authorship.
These authors contributed equally to this work
B.W.B. and B.A.M. are the Chief Operating Officer and Chief Executive Officer, respectively, of ImmunoCeutica Inc. (ICI), which is dedicated to the research and development of immunoceuticals. B.A.M. serves as a scientific advisor for Canadian COVID Care Alliance (CCCA). Neither ICI nor CCCA were involved in any way with this manuscript and the research it describes. B.W.B. and B.A.M. have received honoraria for speaking engagements and have given paid expert testimony in service to courts for their expertise in viral immunology and immunogenetics, respectively. The other authors have no potential conflicts of interest to declare. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Supplement: Seven supplementary figures are available with the online version of this article.
ISSN:0022-1317
1465-2099
1465-2099
DOI:10.1099/jgv.0.002010