Identification of oncolytic vaccinia restriction factors in canine high-grade mammary tumor cells using single-cell transcriptomics.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
23
05
2020
accepted:
01
09
2020
revised:
29
10
2020
pubmed:
20
10
2020
medline:
1
1
2021
entrez:
19
10
2020
Statut:
epublish
Résumé
Mammary carcinoma, including triple-negative breast carcinomas (TNBC) are tumor-types for which human and canine pathologies are closely related at the molecular level. The efficacy of an oncolytic vaccinia virus (VV) was compared in low-passage primary carcinoma cells from TNBC versus non-TNBC. Non-TNBC cells were 28 fold more sensitive to VV than TNBC cells in which VV replication is impaired. Single-cell RNA-seq performed on two different TNBC cell samples, infected or not with VV, highlighted three distinct populations: naïve cells, bystander cells, defined as cells exposed to the virus but not infected and infected cells. The transcriptomes of these three populations showed striking variations in the modulation of pathways regulated by cytokines and growth factors. We hypothesized that the pool of genes expressed in the bystander populations was enriched in antiviral genes. Bioinformatic analysis suggested that the reduced activity of the virus was associated with a higher mesenchymal status of the cells. In addition, we demonstrated experimentally that high expression of one gene, DDIT4, is detrimental to VV production. Considering that DDIT4 is associated with a poor prognosis in various cancers including TNBC, our data highlight DDIT4 as a candidate resistance marker for oncolytic poxvirus therapy. This information could be used to design new generations of oncolytic poxviruses. Beyond the field of gene therapy, this study demonstrates that single-cell transcriptomics can be used to identify cellular factors influencing viral replication.
Identifiants
pubmed: 33075093
doi: 10.1371/journal.ppat.1008660
pii: PPATHOGENS-D-20-01089
pmc: PMC7595618
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008660Déclaration de conflit d'intérêts
No
Références
Virchows Arch. 2008 Aug;453(2):123-32
pubmed: 18677512
Cell Host Microbe. 2016 Sep 14;20(3):392-405
pubmed: 27631702
Nat Rev Clin Oncol. 2017 Oct;14(10):611-629
pubmed: 28397828
EBioMedicine. 2018 May;31:17-24
pubmed: 29724655
Cell Syst. 2018 Jun 27;6(6):679-691.e4
pubmed: 29886109
Ann Surg. 2012 Sep;256(3):437-45
pubmed: 22868370
Nat Rev Cancer. 2008 Feb;8(2):147-56
pubmed: 18202698
J Natl Cancer Inst. 2013 Apr 3;105(7):452-8
pubmed: 23434901
Semin Oncol. 2017 Aug;44(4):301
pubmed: 29526259
J Nucl Med. 2018 Jan;59(1):121-126
pubmed: 29051343
Genes Dev. 2004 Dec 1;18(23):2893-904
pubmed: 15545625
Front Immunol. 2018 Apr 26;9:866
pubmed: 29755464
Cancer Gene Ther. 2008 Jul;15(7):465-73
pubmed: 18421306
Gene Ther. 1999 Jun;6(6):1192-7
pubmed: 10455425
Am J Respir Crit Care Med. 2019 Jul 15;200(2):184-198
pubmed: 30964696
J Clin Med. 2018 Mar 02;7(3):
pubmed: 29498669
Sci Rep. 2017 May 8;7(1):1526
pubmed: 28484222
Front Oncol. 2018 Apr 12;8:106
pubmed: 29707520
J Virol. 2009 Jul;83(13):6883-99
pubmed: 19386722
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11513-8
pubmed: 20534518
Immunol Res. 2011 Aug;50(2-3):286-93
pubmed: 21717084
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3519-24
pubmed: 23401514
Cell Host Microbe. 2007 Oct 11;2(4):221-8
pubmed: 18005740
In Vivo. 2011 May-Jun;25(3):455-65
pubmed: 21576423
BMC Vet Res. 2010 Jan 28;6:5
pubmed: 20109214
PLoS Pathog. 2009 Mar;5(3):e1000327
pubmed: 19266025
J Virol. 2011 May;85(10):5016-26
pubmed: 21367889
Nat Biotechnol. 2006 Sep;24(9):1065-6
pubmed: 16964204
mBio. 2015 Aug 04;6(4):e01122
pubmed: 26242627
J Cell Physiol. 2019 Feb 5;:
pubmed: 30723913
Protein Expr Purif. 2007 Dec;56(2):269-78
pubmed: 17892951
Breast Cancer Res Treat. 2018 Jan;167(2):459-468
pubmed: 29063312
Annu Rev Biochem. 2004;73:657-704
pubmed: 15189156
Clin Cancer Res. 2016 May 1;22(9):2133-8
pubmed: 26712689
Cancer Gene Ther. 2019 Nov;26(11-12):411-418
pubmed: 30622322
BMC Cancer. 2015 Oct 08;15:664
pubmed: 26449867
J Virol. 2015 Jul;89(13):6874-86
pubmed: 25903347
Cancer Res. 2011 Jul 1;71(13):4366-72
pubmed: 21540236
Mol Cell Biol. 2008 Apr;28(8):2648-58
pubmed: 18250159
PLoS Pathog. 2017 Apr 5;13(4):e1006289
pubmed: 28380040
J Clin Invest. 2000 Apr;105(7):847-51
pubmed: 10749561
NPJ Genom Med. 2016 Feb 03;1:15015
pubmed: 29263808
J Natl Cancer Inst. 2018 Oct 1;110(10):1123-1132
pubmed: 29788332
Am J Physiol Cell Physiol. 2010 Aug;299(2):C189-202
pubmed: 20463170
Clin Chem. 2007 Apr;53(4):606-13
pubmed: 17332145
Transl Res. 2012 Mar;159(3):165-72
pubmed: 22340765
Cancer Res. 2014 Sep 15;74(18):5045-56
pubmed: 25082814
J Comp Pathol. 2013 May;148(4):298-306
pubmed: 23079102
Cancer Res. 2013 Feb 15;73(4):1265-75
pubmed: 23393196
Breast Cancer Res Treat. 2018 Feb;167(3):635-648
pubmed: 29086231
Cell Rep. 2012 Oct 25;2(4):1036-47
pubmed: 23084750
Elife. 2018 Feb 16;7:
pubmed: 29451492
J Virol. 2011 Nov;85(22):11588-600
pubmed: 21880762
Cancers (Basel). 2019 May 24;11(5):
pubmed: 31137748
PLoS Pathog. 2013;9(11):e1003719
pubmed: 24244156
Virology. 1960 Jul;11:603-23
pubmed: 13806834
J Clin Endocrinol Metab. 2011 Sep;96(9):E1435-43
pubmed: 21697253
Nat Rev Cancer. 2009 Jan;9(1):64-71
pubmed: 19104515
J Virol Methods. 2014 Jun;202:101-5
pubmed: 24642236
PLoS Pathog. 2008 Jul 04;4(7):e1000096
pubmed: 18604270
Cancer Res. 2007 Oct 15;67(20):10038-46
pubmed: 17942938
Cancer Res. 2006 Aug 15;66(16):8233-40
pubmed: 16912203
J Gen Virol. 2004 Aug;85(Pt 8):2167-2175
pubmed: 15269355
Curr Opin Virol. 2015 Aug;13:49-54
pubmed: 25900822
J Clin Microbiol. 2004 Feb;42(2):601-9
pubmed: 14766823
Mol Cell. 2002 Nov;10(5):995-1005
pubmed: 12453409
PLoS One. 2014 Jun 05;9(6):e98431
pubmed: 24901222
DNA Repair (Amst). 2018 Nov;71:93-100
pubmed: 30170830
Mol Biol Cell. 2012 Sep;23(18):3591-601
pubmed: 22855530
J Virol. 2019 Jul 17;93(15):
pubmed: 31118254