Histone Deacetylase Inhibitors Enhance Cell Killing and Block Interferon-Beta Synthesis Elicited by Infection with an Oncolytic Parainfluenza Virus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cells, Viruses, and Infections
2.2. Chemical Preparation
2.3. Cell Viability and Caspase Assays
2.4. Western Blotting
2.5. Fluorescence Microscopy and IRF-3 immunostaining
2.6. Human IFN-β ELISA
2.7. Reverse Transcription and Real Time PCR
2.8. Statistical Analyses
3. Results
3.1. HDAC Inhibitors Enhance Killing of Lung Cancer Cells by the P/V-CPI- Mutant through Increases in Caspase Activity
3.2. Double Stranded RNA Contributes to scriptaid-Mediated Enhancement of Cell Killing by the P/V-CPI- Virus
3.3. Scriptaid Pretreatment Enhances Killing of Lung Cancer Cells Infected with LACV and VSV
3.4. HDAC Inhibitor Pretreatment Downregulates IFN-β Production and Enhances Spread of the P/V-CPI- Mutant
3.5. Scriptaid Treatment Reduces P/V-CPI-Induced Nuclear Localization of IRF-3
3.6. Post-Infection Treatment of P/V-CPI-Infected Cells with a Panel of HDAC Inhibitors Reveals Two Cell Killing Profiles
4. Discussion
Author Contributions
Acknowledgments
Conflicts of Interest
References
- Kaufman, H.L.; Kohlhapp, F.J.; Zloza, A. Oncolytic viruses: A new class of immunotherapy drugs. Nat. Rev. Drug Discov. 2015, 14, 642–662. [Google Scholar] [CrossRef]
- Fukuhara, H.; Ino, Y.; Todo, T. Oncolytic virus therapy: A new era of cancer treatment at dawn. Cancer Sci. 2016, 107, 1373–1379. [Google Scholar] [CrossRef] [Green Version]
- Russell, S.J.; Peng, K.W.; Bell, J.C. Oncolytic virotherapy. Nat. Biotechnol. 2012, 30, 658–670. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Elankumaran, S.; Rockemann, D.; Samal, S.K. Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death. J. Virol. 2006, 80, 7522–7534. [Google Scholar] [CrossRef]
- Kinoh, H.; Inoue, M.; Washizawa, K.; Yamamoto, T.; Fujikawa, S.; Tokusumi, Y.; Iida, A.; Nagai, Y.; Hasegawa, M. Generation of a recombinant Sendai virus that is selectively activated and lyses human tumor cells expressing matrix metalloproteinases. Gene Ther. 2004, 11, 1137–1145. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lorence, R.M.; Reichard, K.W.; Katubig, B.B.; Reyes, H.M.; Phuangsab, A.; Mitchell, B.R.; Cascino, C.J.; Walter, R.J.; Peeples, M.E. Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy. J. Natl. Cancer Inst. 1994, 86, 1228–1233. [Google Scholar] [CrossRef]
- Myers, R.; Greiner, S.; Harvey, M.; Soeffker, D.; Frenzke, M.; Abraham, K.; Shaw, A.; Rozenblatt, S.; Federspiel, M.J.; Russell, S.J.; et al. Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer. Cancer Gene Ther. 2005, 12, 593–599. [Google Scholar] [CrossRef] [Green Version]
- Peng, K.W.; Donovan, K.A.; Schneider, U.; Cattaneo, R.; Lust, J.A.; Russell, S.J. Oncolytic measles viruses displaying a single-chain antibody against CD38, a myeloma cell marker. Blood 2003, 101, 2557–2562. [Google Scholar] [CrossRef] [PubMed]
- Yu, N.; Puckett, S.; Antinozzi, P.A.; Cramer, S.D.; Lyles, D.S. Changes in Susceptibility to Oncolytic Vesicular Stomatitis Virus during Progression of Prostate Cancer. J. Virol. 2015, 89, 5250–5263. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Matveeva, O.V.; Guo, Z.S.; Senin, V.M.; Senina, A.V.; Shabalina, S.A.; Chumakov, P.M. Oncolysis by paramyxoviruses: Preclinical and clinical studies. Mol. Ther. Oncolytics 2015, 2. [Google Scholar] [CrossRef]
- Choppin, P.W. MULTIPLICATION OF A MYXOVIRUS (SV5) WITH MINIMAL CYTOPATHIC EFFECTS AND WITHOUT INTERFERENCE. Virology 1964, 23, 224–233. [Google Scholar] [CrossRef]
- He, B.; Lin, G.Y.; Durbin, J.E.; Durbin, R.K.; Lamb, R.A. The SH Integral Membrane Protein of the Paramyxovirus Simian Virus 5 Is Required To Block Apoptosis in MDBK Cells. J. Virol. 2001, 75, 4068–4079. [Google Scholar] [CrossRef] [Green Version]
- Parks, G.D.; Young, V.A.; Koumenis, C.; Wansley, E.K.; Layer, J.L.; Cooke, K.M. Controlled Cell Killing by a Recombinant Nonsegmented Negative-Strand RNA Virus. Virology 2002, 293, 192–203. [Google Scholar] [CrossRef] [Green Version]
- Sun, M.; Rothermel, T.A.; Shuman, L.; Aligo, J.A.; Xu, S.; Lin, Y.; Lamb, R.A.; He, B. Conserved cysteine-rich domain of paramyxovirus simian virus 5 V protein plays an important role in blocking apoptosis. J. Virol. 2004, 78, 5068–5078. [Google Scholar] [CrossRef]
- Dillon, P.J.; Wansley, E.K.; Young, V.A.; Alexander-Miller, M.A.; Parks, G.D. Exchange of P/V genes between two non-cytopathic simian virus 5 variants results in a recombinant virus that kills cells through death pathways that are sensitive to caspase inhibitors. J. Gen. Virol. 2006, 87, 3643–3648. [Google Scholar] [CrossRef] [Green Version]
- Wansley, E.K.; Parks, G.D. Naturally occurring substitutions in the P/V gene convert the noncytopathic paramyxovirus simian virus 5 into a virus that induces alpha/beta interferon synthesis and cell death. J. Virol. 2002, 76, 10109–10121. [Google Scholar] [CrossRef]
- Lamb, R.A.; Parks, G.D. Paramyxoviridae: The viruses and their replication. In Fields virology, 5th ed.; Knipe, D.M., Howley, P.M., Griffin, D.E., Lamb, R.A., Martin, M.A., Roizman, B., Straus, S.E., Eds.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2007; pp. 1449–1496. [Google Scholar]
- Goodbourn, S.; Didcock, L.; Randall, R.E. Interferons: Cell signaling, immune modulation, antiviral response and virus countermeasures. J. Gen. Virol. 2000, 81, 2341–2364. [Google Scholar] [CrossRef]
- Didcock, L.; Young, D.F.; Goodbourn, S.; Randall, R.E. The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation. J. Virol. 1999, 73, 9928–9933. [Google Scholar]
- Childs, K.; Stock, N.; Ross, C.; Andrejeva, J.; Hilton, L.; Skinner, M.; Randall, R.; Goodbourn, S. mda-5, but not RIG-I, is a common target for paramyxovirus V proteins. Virology 2007, 359, 190–200. [Google Scholar] [CrossRef] [Green Version]
- Wansley, E.K.; Dillon, P.J.; Gainey, M.D.; Tam, J.; Cramer, S.D.; Parks, G.D. Growth sensitivity of a recombinant simian virus 5 P/V mutant to type I interferon differs between tumor cell lines and normal primary cells. Virology 2005, 335, 131–144. [Google Scholar] [CrossRef] [Green Version]
- Young, V.A.; Dillon, P.J.; Parks, G.D. Variants of the paramyxovirus Simian virus 5 with accelerated or delayed viral gene expression activate proinflammatory cytokine synthesis. Virology 2006, 350, 90–102. [Google Scholar] [CrossRef]
- Gainey, M.D.; Manuse, M.J.; Parks, G.D. A hyperfusogenic F protein enhances the oncolytic potency of a paramyxovirus simian virus 5 P/V mutant without compromising sensitivity to type I interferon. J. Virol. 2008, 82, 9369–9380. [Google Scholar] [CrossRef]
- Gainey, M.D.; Dillon, P.J.; Clark, K.M.; Manuse, M.J.; Parks, G.D. Paramyxovirus-induced shutoff of host and viral protein synthesis: Role of the P and V proteins in limiting PKR activation. J. Virol. 2008, 82, 828–839. [Google Scholar] [CrossRef]
- Wansley, E.K.; Grayson, J.M.; Parks, G.D. Apoptosis induction and interferon signaling but not IFN-beta promoter induction by an SV5 P/V mutant are rescued by coinfection with wild-type SV5. Virology 2003, 316, 41–54. [Google Scholar] [CrossRef]
- Fox, C.R.; Parks, G.D. Parainfluenza Virus Infection Sensitizes Cancer Cells to DNA-Damaging Agents: Implications for Oncolytic Virus Therapy. J. Virol. 2018, 92. [Google Scholar] [CrossRef]
- Minamiya, Y.; Ono, T.; Saito, H.; Takahashi, N.; Ito, M.; Mitsui, M.; Motoyama, S.; Ogawa, J. Expression of histone deacetylase 1 correlates with a poor prognosis in patients with adenocarcinoma of the lung. Lung Cancer 2011, 74, 300–304. [Google Scholar] [CrossRef]
- Chang, H.H.; Chiang, C.P.; Hung, H.C.; Lin, C.Y.; Deng, Y.T.; Kuo, M.Y. Histone deacetylase 2 expression predicts poorer prognosis in oral cancer patients. Oral. Oncol. 2009, 45, 610–614. [Google Scholar] [CrossRef]
- Eckschlager, T.; Plch, J.; Stiborova, M.; Hrabeta, J. Histone Deacetylase Inhibitors as Anticancer Drugs. Int. J. Mol. Sci. 2017, 18. [Google Scholar] [CrossRef]
- Suraweera, A.; O’Byrne, K.J.; Richard, D.J. Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi. Front. Oncol. 2018, 8, 92. [Google Scholar] [CrossRef]
- Manuse, M.J.; Parks, G.D. Role for the paramyxovirus genomic promoter in limiting host cell antiviral responses and cell killing. J. Virol. 2009, 83, 9057–9067. [Google Scholar] [CrossRef]
- Kobayashi, T.; Antar, A.A.; Boehme, K.W.; Danthi, P.; Eby, E.A.; Guglielmi, K.M.; Holm, G.H.; Johnson, E.M.; Maginnis, M.S.; Naik, S.; et al. A plasmid-based reverse genetics system for animal double-stranded RNA viruses. Cell Host Microbe 2007, 1, 147–157. [Google Scholar] [CrossRef] [PubMed]
- He, B.; Paterson, R.G.; Ward, C.D.; Lamb, R.A. Recovery of infectious SV5 from cloned DNA and expression of a foreign gene. Virology 1997, 237, 249–260. [Google Scholar] [CrossRef] [PubMed]
- Dillon, P.J.; Parks, G.D. Role for the phosphoprotein P subunit of the paramyxovirus polymerase in limiting induction of host cell antiviral responses. J. Virol. 2007, 81, 11116–11127. [Google Scholar] [CrossRef] [PubMed]
- Madigan, A.A.; Sobek, K.M.; Cummings, J.L.; Green, W.R.; Bacich, D.J.; O’Keefe, D.S. Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasia. Genes Immun. 2012, 13, 566–572. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gonzalez-Reyes, S.; Marin, L.; Gonzalez, L.; Gonzalez, L.O.; del Casar, J.M.; Lamelas, M.L.; Gonzalez-Quintana, J.M.; Vizoso, F.J. Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC Cancer 2010, 10, 665. [Google Scholar] [CrossRef] [PubMed]
- Yue, Z.; Shatkin, A.J. Double-stranded RNA-dependent protein kinase (PKR) is regulated by reovirus structural proteins. Virology 1997, 234, 364–371. [Google Scholar] [CrossRef] [PubMed]
- Zhao, X.; Ai, M.; Guo, Y.; Zhou, X.; Wang, L.; Li, X.; Yao, C. Poly I:C-induced tumor cell apoptosis mediated by pattern-recognition receptors. Cancer Biother. Radiopharm. 2012, 27, 530–534. [Google Scholar] [CrossRef] [PubMed]
- Hiscott, J.; Pitha, P.; Genin, P.; Nguyen, H.; Heylbroeck, C.; Mamane, Y.; Algarte, M.; Lin, R. Triggering the interferon response: The role of IRF-3 transcription factor. J. Interferon Cytokine Res. 1999, 19, 1–13. [Google Scholar] [CrossRef]
- Robey, R.W.; Chakraborty, A.R.; Basseville, A.; Luchenko, V.; Bahr, J.; Zhan, Z.; Bates, S.E. Histone deacetylase inhibitors: Emerging mechanisms of resistance. Mol. Pharm. 2011, 8, 2021–2031. [Google Scholar] [CrossRef]
- Otsuki, A.; Patel, A.; Kasai, K.; Suzuki, M.; Kurozumi, K.; Antonio Chiocca, E.; Saeki, Y. Histone Deacetylase Inhibitors Augment Antitumor Efficacy of Herpes-based Oncolytic Viruses. Mol. Ther. 2008, 16, 1546–1555. [Google Scholar] [CrossRef]
- Sasaki, Y.; Negishi, H.; Idogawa, M.; Suzuki, H.; Mita, H.; Toyota, M.; Shinomura, Y.; Imai, K.; Tokino, T. Histone deacetylase inhibitor FK228 enhances adenovirus-mediated p53 family gene therapy in cancer models. Mol. Cancer Ther. 2008, 7, 779–787. [Google Scholar] [CrossRef] [Green Version]
- Goldsmith, M.E.; Aguila, A.; Steadman, K.; Martinez, A.; Steinberg, S.M.; Alley, M.C.; Waud, W.R.; Bates, S.E.; Fojo, T. The histone deacetylase inhibitor FK228 given prior to adenovirus infection can boost infection in melanoma xenograft model systems. Mol. Cancer Ther. 2007, 6, 496–505. [Google Scholar] [CrossRef] [Green Version]
- MacTavish, H.; Diallo, J.S.; Huang, B.; Stanford, M.; Le Boeuf, F.; De Silva, N.; Cox, J.; Simmons, J.G.; Guimond, T.; Falls, T.; et al. Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors. PLoS ONE 2010, 5, e14462. [Google Scholar] [CrossRef]
- Hoti, N.; Chowdhury, W.; Hsieh, J.T.; Sachs, M.D.; Lupold, S.E.; Rodriguez, R. Valproic acid, a histone deacetylase inhibitor, is an antagonist for oncolytic adenoviral gene therapy. Mol. Ther. 2006, 14, 768–778. [Google Scholar] [CrossRef]
- Nakashima, H.; Nguyen, T.; Chiocca, E.A. Combining HDAC inhibitors with oncolytic virotherapy for cancer therapy. Oncolytic Virother. 2015, 4, 183–191. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marchini, A.; Scott, E.M.; Rommelaere, J. Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade. Viruses 2016, 8, 9. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, T.L.-A.; Wilson, M.G.; Hiscott, J. Oncolytic viruses and histone deacetylase inhibitors—A multi-pronged strategy to target tumor cells. Cytokine Growth Factor Rev. 2010, 21, 153–159. [Google Scholar] [CrossRef] [PubMed]
- Shulak, L.; Beljanski, V.; Chiang, C.; Dutta, S.M.; Van Grevenynghe, J.; Belgnaoui, S.M.; Nguyên, T.L.-A.; Di Lenardo, T.; Semmes, O.J.; Lin, R.; Hiscott, J. Histone deacetylase inhibitors potentiate vesicular stomatitis virus oncolysis in prostate cancer cells by modulating NF-κB-dependent autophagy. J. Virol. 2014, 88, 2927–2940. [Google Scholar] [CrossRef]
- Ellerhoff, T.P.; Berchtold, S.; Venturelli, S.; Burkard, M.; Smirnow, I.; Wulff, T.; Lauer, U.M. Novel epi-virotherapeutic treatment of pancreatic cancer combining the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus. Int. J. Oncol. 2016, 49, 1931–1944. [Google Scholar] [CrossRef] [PubMed]
- Nusinzon, I.; Horvath, C.M. Interferon-stimulated transcription and innate antiviral immunity require deacetylase activity and histone deacetylase 1. Proc. Natl. Acad. Sci. USA 2003, 100, 14742–14747. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, S.; Dai, Y.; Pei, X.Y.; Grant, S. Bim upregulation by histone deacetylase inhibitors mediates interactions with the Bcl-2 antagonist ABT-737: Evidence for distinct roles for Bcl-2, Bcl-xL, and Mcl-1. Mol. Cell Biol. 2009, 29, 6149–6169. [Google Scholar] [CrossRef]
- Xargay-Torrent, S.; Lopez-Guerra, M.; Saborit-Villarroya, I.; Rosich, L.; Campo, E.; Roue, G.; Colomer, D. Vorinostat-induced apoptosis in mantle cell lymphoma is mediated by acetylation of proapoptotic BH3-only gene promoters. Clin. Cancer Res. 2011, 17, 3956–3968. [Google Scholar] [CrossRef]
- Inoue, S.; Riley, J.; Gant, T.W.; Dyer, M.J.; Cohen, G.M. Apoptosis induced by histone deacetylase inhibitors in leukemic cells is mediated by Bim and Noxa. Leukemia 2007, 21, 1773–1782. [Google Scholar] [CrossRef] [Green Version]
- Terui, T.; Murakami, K.; Takimoto, R.; Takahashi, M.; Takada, K.; Murakami, T.; Minami, S.; Matsunaga, T.; Takayama, T.; Kato, J.; et al. Induction of PIG3 and NOXA through acetylation of p53 at 320 and 373 lysine residues as a mechanism for apoptotic cell death by histone deacetylase inhibitors. Cancer Res. 2003, 63, 8948–8954. [Google Scholar]
- Aron, J.L.; Parthun, M.R.; Marcucci, G.; Kitada, S.; Mone, A.P.; Davis, M.E.; Shen, T.; Murphy, T.; Wickham, J.; Kanakry, C.; et al. Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein. Blood 2003, 102, 652–658. [Google Scholar] [CrossRef] [Green Version]
- Rosato, R.R.; Almenara, J.A.; Kolla, S.S.; Maggio, S.C.; Coe, S.; Gimenez, M.S.; Dent, P.; Grant, S. Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions. Mol. Cancer Ther. 2007, 6, 692–702. [Google Scholar] [CrossRef] [Green Version]
- Sanda, T.; Okamoto, T.; Uchida, Y.; Nakagawa, H.; Iida, S.; Kayukawa, S.; Suzuki, T.; Oshizawa, T.; Suzuki, T.; Miyata, N.; et al. Proteome analyses of the growth inhibitory effects of NCH-51, a novel histone deacetylase inhibitor, on lymphoid malignant cells. Leukemia 2007, 21, 2344–2353. [Google Scholar] [CrossRef] [Green Version]
- Glick, R.D.; Swendeman, S.L.; Coffey, D.C.; Rifkind, R.A.; Marks, P.A.; Richon, V.M.; La Quaglia, M.P. Hybrid polar histone deacetylase inhibitor induces apoptosis and CD95/CD95 ligand expression in human neuroblastoma. Cancer Res 1999, 59, 4392–4399. [Google Scholar]
- Insinga, A.; Monestiroli, S.; Ronzoni, S.; Gelmetti, V.; Marchesi, F.; Viale, A.; Altucci, L.; Nervi, C.; Minucci, S.; Pelicci, P.G. Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nat. Med. 2005, 11, 71–76. [Google Scholar] [CrossRef]
- Nebbioso, A.; Clarke, N.; Voltz, E.; Germain, E.; Ambrosino, C.; Bontempo, P.; Alvarez, R.; Schiavone, E.M.; Ferrara, F.; Bresciani, F.; et al. Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat. Med. 2005, 11, 77–84. [Google Scholar] [CrossRef]
- Nakata, S.; Yoshida, T.; Horinaka, M.; Shiraishi, T.; Wakada, M.; Sakai, T. Histone deacetylase inhibitors upregulate death receptor 5/TRAIL-R2 and sensitize apoptosis induced by TRAIL/APO2-L in human malignant tumor cells. Oncogene 2004, 23, 6261. [Google Scholar] [CrossRef]
- Garcia, M.A.; Guerra, S.; Gil, J.; Jimenez, V.; Esteban, M. Anti-apoptotic and oncogenic properties of the dsRNA-binding protein of vaccinia virus, E3L. Oncogene 2002, 21, 8379–8387. [Google Scholar] [CrossRef] [Green Version]
- Mazar, J.; Li, Y.; Rosado, A.; Phelan, P.; Kedarinath, K.; Parks, G.D.; Alexander, K.A.; Westmoreland, T.J. Zika virus as an oncolytic treatment of human neuroblastoma cells requires CD24. PLoS ONE 2018, 13, e0200358. [Google Scholar] [CrossRef]
- Flemington, E.K. Herpesvirus lytic replication and the cell cycle: Arresting new developments. J. Virol. 2001, 75, 4475–4481. [Google Scholar] [CrossRef]
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Fox, C.R.; Parks, G.D. Histone Deacetylase Inhibitors Enhance Cell Killing and Block Interferon-Beta Synthesis Elicited by Infection with an Oncolytic Parainfluenza Virus. Viruses 2019, 11, 431. https://doi.org/10.3390/v11050431
Fox CR, Parks GD. Histone Deacetylase Inhibitors Enhance Cell Killing and Block Interferon-Beta Synthesis Elicited by Infection with an Oncolytic Parainfluenza Virus. Viruses. 2019; 11(5):431. https://doi.org/10.3390/v11050431
Chicago/Turabian StyleFox, Candace R., and Griffith D. Parks. 2019. "Histone Deacetylase Inhibitors Enhance Cell Killing and Block Interferon-Beta Synthesis Elicited by Infection with an Oncolytic Parainfluenza Virus" Viruses 11, no. 5: 431. https://doi.org/10.3390/v11050431