The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status

M. Kim, C. T. Williamson, J. Prudhomme, D. G. Bebb, K. Riabowol, P. W.K. Lee, S. P. Lees-Miller, Y. Mori, Masmudur Rahman, Douglas McFadden, R. N. Johnston

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Replication-competent oncolytic viruses hold great potential for the clinical treatment of many cancers. Importantly, many oncolytic virus candidates, such as reovirus and myxoma virus, preferentially infect cancer cells bearing abnormal cellular signaling pathways. Reovirus and myxoma virus are highly responsive to activated Ras and Akt signaling pathways, respectively, for their specificity for viral oncolysis. However, considering the complexity of cancer cell populations, it is possible that other tumor-specific signaling pathways may also contribute to viral discrimination between normal versus cancer cells. Because carcinogenesis is a multistep process involving the accumulation of both oncogene activations and the inactivation of tumor suppressor genes, we speculated that not only oncogenes but also tumor suppressor genes may have an important role in determining the tropism of these viruses for cancer cells. It has been previously shown that many cellular tumor suppressor genes, such as p53, ATM and Rb, are important for maintaining genomic stability; dysfunction of these tumor suppressors may disrupt intact cellular antiviral activity due to the accumulation of genomic instability or due to interference with apoptotic signaling. Therefore, we speculated that cells with dysfunctional tumor suppressors may display enhanced susceptibility to challenge with these oncolytic viruses, as previously seen with adenovirus. We report here that both reovirus and myxoma virus preferentially infect cancer cells bearing dysfunctional or deleted p53, ATM and Rb tumor suppressor genes compared to cells retaining normal counterparts of these genes. Thus, oncolysis by these viruses may be influenced by both oncogenic activation and tumor suppressor status.

Original languageEnglish (US)
Pages (from-to)3990-3996
Number of pages7
JournalOncogene
Volume29
Issue number27
DOIs
StatePublished - Jul 8 2010
Externally publishedYes

Fingerprint

Myxoma virus
Viral Tropism
Oncolytic Viruses
Tumor Suppressor Genes
Neoplasms
Genomic Instability
Oncogenes
Viruses
Tropism
Adenoviridae
Antiviral Agents
Carcinogenesis

Keywords

  • anticancer therapy
  • myxoma virus
  • oncolytic virus
  • reovirus
  • tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Kim, M., Williamson, C. T., Prudhomme, J., Bebb, D. G., Riabowol, K., Lee, P. W. K., ... Johnston, R. N. (2010). The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status. Oncogene, 29(27), 3990-3996. https://doi.org/10.1038/onc.2010.137

The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status. / Kim, M.; Williamson, C. T.; Prudhomme, J.; Bebb, D. G.; Riabowol, K.; Lee, P. W.K.; Lees-Miller, S. P.; Mori, Y.; Rahman, Masmudur; McFadden, Douglas; Johnston, R. N.

In: Oncogene, Vol. 29, No. 27, 08.07.2010, p. 3990-3996.

Research output: Contribution to journalArticle

Kim, M, Williamson, CT, Prudhomme, J, Bebb, DG, Riabowol, K, Lee, PWK, Lees-Miller, SP, Mori, Y, Rahman, M, McFadden, D & Johnston, RN 2010, 'The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status', Oncogene, vol. 29, no. 27, pp. 3990-3996. https://doi.org/10.1038/onc.2010.137
Kim, M. ; Williamson, C. T. ; Prudhomme, J. ; Bebb, D. G. ; Riabowol, K. ; Lee, P. W.K. ; Lees-Miller, S. P. ; Mori, Y. ; Rahman, Masmudur ; McFadden, Douglas ; Johnston, R. N. / The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status. In: Oncogene. 2010 ; Vol. 29, No. 27. pp. 3990-3996.
@article{5a5dad813df6464ca5a277fe0039c883,
title = "The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status",
abstract = "Replication-competent oncolytic viruses hold great potential for the clinical treatment of many cancers. Importantly, many oncolytic virus candidates, such as reovirus and myxoma virus, preferentially infect cancer cells bearing abnormal cellular signaling pathways. Reovirus and myxoma virus are highly responsive to activated Ras and Akt signaling pathways, respectively, for their specificity for viral oncolysis. However, considering the complexity of cancer cell populations, it is possible that other tumor-specific signaling pathways may also contribute to viral discrimination between normal versus cancer cells. Because carcinogenesis is a multistep process involving the accumulation of both oncogene activations and the inactivation of tumor suppressor genes, we speculated that not only oncogenes but also tumor suppressor genes may have an important role in determining the tropism of these viruses for cancer cells. It has been previously shown that many cellular tumor suppressor genes, such as p53, ATM and Rb, are important for maintaining genomic stability; dysfunction of these tumor suppressors may disrupt intact cellular antiviral activity due to the accumulation of genomic instability or due to interference with apoptotic signaling. Therefore, we speculated that cells with dysfunctional tumor suppressors may display enhanced susceptibility to challenge with these oncolytic viruses, as previously seen with adenovirus. We report here that both reovirus and myxoma virus preferentially infect cancer cells bearing dysfunctional or deleted p53, ATM and Rb tumor suppressor genes compared to cells retaining normal counterparts of these genes. Thus, oncolysis by these viruses may be influenced by both oncogenic activation and tumor suppressor status.",
keywords = "anticancer therapy, myxoma virus, oncolytic virus, reovirus, tumor suppressor",
author = "M. Kim and Williamson, {C. T.} and J. Prudhomme and Bebb, {D. G.} and K. Riabowol and Lee, {P. W.K.} and Lees-Miller, {S. P.} and Y. Mori and Masmudur Rahman and Douglas McFadden and Johnston, {R. N.}",
year = "2010",
month = "7",
day = "8",
doi = "10.1038/onc.2010.137",
language = "English (US)",
volume = "29",
pages = "3990--3996",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "27",

}

TY - JOUR

T1 - The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status

AU - Kim, M.

AU - Williamson, C. T.

AU - Prudhomme, J.

AU - Bebb, D. G.

AU - Riabowol, K.

AU - Lee, P. W.K.

AU - Lees-Miller, S. P.

AU - Mori, Y.

AU - Rahman, Masmudur

AU - McFadden, Douglas

AU - Johnston, R. N.

PY - 2010/7/8

Y1 - 2010/7/8

N2 - Replication-competent oncolytic viruses hold great potential for the clinical treatment of many cancers. Importantly, many oncolytic virus candidates, such as reovirus and myxoma virus, preferentially infect cancer cells bearing abnormal cellular signaling pathways. Reovirus and myxoma virus are highly responsive to activated Ras and Akt signaling pathways, respectively, for their specificity for viral oncolysis. However, considering the complexity of cancer cell populations, it is possible that other tumor-specific signaling pathways may also contribute to viral discrimination between normal versus cancer cells. Because carcinogenesis is a multistep process involving the accumulation of both oncogene activations and the inactivation of tumor suppressor genes, we speculated that not only oncogenes but also tumor suppressor genes may have an important role in determining the tropism of these viruses for cancer cells. It has been previously shown that many cellular tumor suppressor genes, such as p53, ATM and Rb, are important for maintaining genomic stability; dysfunction of these tumor suppressors may disrupt intact cellular antiviral activity due to the accumulation of genomic instability or due to interference with apoptotic signaling. Therefore, we speculated that cells with dysfunctional tumor suppressors may display enhanced susceptibility to challenge with these oncolytic viruses, as previously seen with adenovirus. We report here that both reovirus and myxoma virus preferentially infect cancer cells bearing dysfunctional or deleted p53, ATM and Rb tumor suppressor genes compared to cells retaining normal counterparts of these genes. Thus, oncolysis by these viruses may be influenced by both oncogenic activation and tumor suppressor status.

AB - Replication-competent oncolytic viruses hold great potential for the clinical treatment of many cancers. Importantly, many oncolytic virus candidates, such as reovirus and myxoma virus, preferentially infect cancer cells bearing abnormal cellular signaling pathways. Reovirus and myxoma virus are highly responsive to activated Ras and Akt signaling pathways, respectively, for their specificity for viral oncolysis. However, considering the complexity of cancer cell populations, it is possible that other tumor-specific signaling pathways may also contribute to viral discrimination between normal versus cancer cells. Because carcinogenesis is a multistep process involving the accumulation of both oncogene activations and the inactivation of tumor suppressor genes, we speculated that not only oncogenes but also tumor suppressor genes may have an important role in determining the tropism of these viruses for cancer cells. It has been previously shown that many cellular tumor suppressor genes, such as p53, ATM and Rb, are important for maintaining genomic stability; dysfunction of these tumor suppressors may disrupt intact cellular antiviral activity due to the accumulation of genomic instability or due to interference with apoptotic signaling. Therefore, we speculated that cells with dysfunctional tumor suppressors may display enhanced susceptibility to challenge with these oncolytic viruses, as previously seen with adenovirus. We report here that both reovirus and myxoma virus preferentially infect cancer cells bearing dysfunctional or deleted p53, ATM and Rb tumor suppressor genes compared to cells retaining normal counterparts of these genes. Thus, oncolysis by these viruses may be influenced by both oncogenic activation and tumor suppressor status.

KW - anticancer therapy

KW - myxoma virus

KW - oncolytic virus

KW - reovirus

KW - tumor suppressor

UR - http://www.scopus.com/inward/record.url?scp=77954541596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954541596&partnerID=8YFLogxK

U2 - 10.1038/onc.2010.137

DO - 10.1038/onc.2010.137

M3 - Article

C2 - 20473328

AN - SCOPUS:77954541596

VL - 29

SP - 3990

EP - 3996

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 27

ER -