STAT1 and NF-κB Inhibitors Diminish Basal Interferon-Stimulated Gene Expression and Improve the Productive Infection of Oncolytic HSV in MPNST Cells.

Molecular Cancer Research : MCR
Joshua D JacksonK A Cassady

Abstract

Interferon-stimulated genes (ISG) encode diverse proteins that mediate intrinsic antiviral resistance in infected cells. Here it was hypothesized that malignant peripheral nerve sheath tumor (MPNST) cells resist the productive infection of oncolytic herpes simplex virus (oHSV) through activation of the JAK/STAT1 pathway and resultant upregulation of ISGs. Multiple human and mouse MPNST cells were used to explore the relationship between STAT1 activation and the productive infection of Δγ134.5 oHSVs. STAT1 activation in response to oHSV infection was found to associate with diminished Δγ134.5 oHSVs replication and spread. Multiday pretreatment, but not cotreatment, with a JAK inhibitor significantly improved viral titer and spread. ISG expression was found to be elevated prior to infection and downregulated when treated with the inhibitor, suggesting that the JAK/STAT1 pathway is active prior to infection. Conversely, upregulation of ISG expression in normally permissive cells significantly decreased oHSV productivity. Finally, a possible link between NF-κB pathway activation and ISG expression was established through the expression of inhibitor of kB (IκB) which decreased basal STAT1 transcription and ISG expression. These resu...Continue Reading

References

Oct 27, 1998·International Journal of Radiation Oncology, Biology, Physics·W W WongL L Gunderson
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·C M PerouD Botstein
Feb 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·J N ParkerJ M Markert
Aug 30, 2000·Nature·C M PerouD Botstein
Jul 15, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Hannah NguyenGeorge R Stark
Feb 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nikolai N KhodarevRalph R Weichselbaum
Oct 31, 2006·International Journal of Cancer. Journal International Du Cancer·Mårten FryknäsAnders Isaksson
Apr 13, 2007·Gene Therapy·A C ShahK A Cassady
Nov 29, 2007·Journal of the National Cancer Institute·Kazuhiko KurozumiBalveen Kaur
Nov 8, 2008·The American Journal of Pathology·Faris FarassatiAndreas Kurtz
Feb 25, 2010·Clinical & Experimental Metastasis·Julia SchultzManfred Kunz
Jul 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Junmei WangAmer A Beg
Jan 7, 2011·Journal of Virology·Suresh H BasagoudanavarSiddharth Balachandran
Jul 28, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ilkka LiikanenAkseli Hemminki
Jan 28, 2012·Cancer Research·Amy HaseleyBalveen Kaur
Apr 19, 2012·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Ziyun DuLawrence M Pfeffer
Aug 27, 2013·Orphanet Journal of Rare Diseases·Ouidad ZehouLaurence Valeyrie-Allanore
Sep 14, 2013·Cancer Gene Therapy·D Escobar-ZarateK-W Peng
Dec 18, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Samuel T WorkenheKaren L Mossman
Dec 19, 2013·International Journal of Cancer. Journal International Du Cancer·Érika CossetOlivier Preynat-Seauve
Sep 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Leticia Corrales, Thomas F Gajewski

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Citations

Jan 31, 2017·Journal of Cellular Biochemistry·Safieh EbrahimiSeyed Mahdi Hassanian
Mar 28, 2017·Molecular Therapy Oncolytics·Kevin A CassadyJames M Markert
Nov 11, 2018·Cancers·Justyna Struzik, Lidia Szulc-Dąbrowska
Oct 26, 2018·Cancer Immunology Research·Mohammed G Ghonime, Kevin A Cassady
Oct 28, 2019·Molecular Therapy Oncolytics·Brian HutzenKevin A Cassady
Jul 13, 2021·Frontiers in Immunology·Simon LoevenichMarit Walbye Anthonsen
Aug 29, 2018·ACS Infectious Diseases·Michael PhanJean-Simon Diallo
Feb 20, 2020·Molecular Therapy. Methods & Clinical Development·Ana Lemos de MatosGrant McFadden

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