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 in | Journal of general virology Vol. 105; no. 8 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Microbiology Society
22.08.2024
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0022-1317 1465-2099 1465-2099 |
| DOI | 10.1099/jgv.0.002010 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. Rhabdoviral vectors can induce lysis of cancer cells. While studied almost exclusively at 37 °C, viruses are subject to a range of temperatures , 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 where therapeutic windows are limited. 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.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. |
| Author | Mehrani, Yeganeh Clark, Mary Ellen Karimi, Khalil van Vloten, Jacob P. Meng, Baozhong Geronimo, Katrina Knapp, Jason P. Bridle, Byram W. Mallard, Bonnie A. Kakish, Julia E. Kodeeswaran, Arthane |
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| Cites_doi | 10.1503/cmaj.170074 10.3171/jns.2002.97.6.1460 10.1038/cgt.2008.74 10.1002/9780471729259.mca04es11 10.1002/9780471729259.mc15d03s31 10.1038/sj.gt.3301389 10.1007/s10147-020-01658-1 10.1016/j.jconrel.2018.05.015 10.3390/v10030108 10.1186/1475-2867-13-75 10.1002/biot.201400429 10.1158/2326-6066.CIR-14-0015 10.1080/15428119591016782 10.3171/jns.2004.101.6.0960 10.1016/j.it.2017.11.006 10.1016/j.bpobgyn.2021.06.004 10.1016/j.tim.2020.02.006 10.1099/jgv.0.001697 10.3791/2259 10.1016/j.omtm.2020.01.001 10.2176/nmc.27.1033 10.3390/biomedicines5010008 10.1023/A:1007919921991 10.1089/10430349950018021 10.2147/OV.S154494 10.1086/423001 10.7547/1000258 10.1099/vir.0.80955-0 10.1038/mt.2010.103 10.1038/mt.2009.194 10.4049/jimmunol.1600106 10.1016/j.ymthe.2018.01.019 10.1073/pnas.92.18.8388 10.1038/mt.2013.249 10.1038/s41573-019-0029-0 10.1056/NEJMoa1414216 10.1073/pnas.1110854108 10.1007/s12250-020-00230-5 10.1038/sj.mt.6300343 10.1016/j.biotechadv.2020.107608 10.1158/1055-9965.EPI-15-0578 10.1038/mt.2009.154 10.1016/j.omto.2017.08.001 10.15557/JoU.2018.0014 10.1016/j.neuroimage.2009.03.043 10.1097/00005537-200004000-00021 |
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| Issue | 8 |
| Keywords | temperature rhabdovirus viral vector oncolytic |
| Language | English |
| License | http://creativecommons.org/licenses/by/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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. |
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| Snippet | 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
,... Rhabdoviral vectors can induce lysis of cancer cells. While studied almost exclusively at 37 °C, viruses are subject to a range of temperatures , including... 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,... |
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| SubjectTerms | 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 |
| Title | Investigating the effect of reduced temperatures on the efficacy of rhabdovirus-based viral vector platforms |
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