A nuclear transport inhibitor that modulates the unfolded protein response and provides in vivo protection against lethal dengue virus infection

Journal of Infectious Diseases

Volumn 210, Issue 11, 2014, Pages 1780-1791

  Fraser, Johanna E ^a   Watanabe, Satoru ^d   Wang, Chunxiao ^a   Chan, Wing Ki Kitti ^d   Maher, Belinda ^a   Lopez Denman, Adam ^b,c   Hick, Caroline ^a   Wagstaff, Kylie M ^a   Mackenzie, Jason M ^b   Sexton, Patrick M ^a   Vasudevan, Subhash G ^d   Jans, David A ^a  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c LA TROBE UNIVERSITY   (Australia)

^d DUKE NUS MEDICAL SCHOOL   (Singapore)

Author keywords

Antiviral; Dengue virus; Nuclear transport; Unfolded protein response

Indexed keywords

ANTIVIRUS AGENT; CARRIER PROTEIN; FENRETINIDE; N-(4-METHOXYPHENYL)RETINAMIDE; NS5 PROTEIN, DENGUE VIRUS; PERK KINASE; PROTEIN BINDING; PROTEIN KINASE R; RETINOIC ACID; VIRUS PROTEIN;

ACTIVE TRANSPORT; ANALOGS AND DERIVATIVES; ANIMAL; CELL LINE; CLASSIFICATION; DENGUE; DENGUE VIRUS; DISEASE MODEL; DRUG EFFECTS; HUMAN; METABOLISM; MOUSE; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; UNFOLDED PROTEIN RESPONSE; VIROLOGY; VIRUS REPLICATION;

ACTIVE TRANSPORT, CELL NUCLEUS; ANIMALS; ANTIVIRAL AGENTS; CARRIER PROTEINS; CELL LINE; DENGUE; DENGUE VIRUS; DISEASE MODELS, ANIMAL; EIF-2 KINASE; FENRETINIDE; HUMANS; MICE; PROTEIN BINDING; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; TRETINOIN; UNFOLDED PROTEIN RESPONSE; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 84905663615     PISSN: 00221899     EISSN: 15376613     Source Type: Journal    
DOI: 10.1093/infdis/jiu319     Document Type: Article

References (50)

1. Gubler DJ Dengue/dengue haemorrhagic fever: history and current status. Novartis Found Symp 2006; 277: 3-16; discussion -22, 71-3, 251-3.
2. Sabchareon A, Wallace D, Sirivichayakul C, et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet 2012; 380: 1559-67.
3. Lim SP, Wang QY, Noble CG, et al. Ten years of dengue drug discovery: progress and prospects. Antiviral Res 2013; 100: 500-19.
4. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338: 853-60.
5. Walensky RP, Paltiel AD, Losina E, et al. The survival benefits of AIDS treatment in the United States. J Infect Dis 2006; 194: 11-9.
6. Lee LY, Tong CY, Wong T, Wilkinson M. New therapies for chronic hepatitis C infection: a systematic review of evidence from clinical trials. Int J Clin Pract 2012; 66: 342-55.
7. Nguyen NM, Tran CN, Phung LK, et al. A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J Infect Dis 2013; 207: 1442-50.
8. Yin Z, Chen YL, Schul W, et al. An adenosine nucleoside inhibitor of dengue virus. Proc Natl Acad Sci U S A 2009; 106: 20435-9.
9. Rathore AP, Paradkar PN, Watanabe S, et al. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Antiviral Res 2011; 92: 453-60.
10. Watanabe S, Rathore AP, Sung C, et al. Dose- and schedule-dependent protective efficacy of celgosivir in a lethal mouse model for dengue virus infection informs dosing regimen for a proof of concept clinical trial. Antiviral Res 2012; 96: 32-5.
11. Kumar A, Buhler S, Selisko B, et al. Nuclear localization of dengue virus nonstructural protein 5 does not strictly correlate with efficient viral RNA replication and inhibition of type I interferon signaling. J Virol 2013; 87: 4545-57.
12. Pryor MJ, Rawlinson SM, Butcher RE, et al. Nuclear localization of dengue virus nonstructural protein 5 through its importin alpha/beta-recognized nuclear localization sequences is integral to viral infection. Traffic 2007; 8: 795-807.
13. Tay MY, Fraser JE, Chan KK, et al. Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin. Antiviral Res 2013; 99: 301-6.
14. Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J 2012; 443: 851-6.
15. Dejnirattisai W, Jumnainsong A, Onsirisakul N, et al. Cross-reacting antibodies enhance dengue virus infection in humans. Science 2010; 328: 745-8.
16. Low JG, Ooi EE, Tolfvenstam T, et al. Early Dengue infection and outcome study (EDEN) - study design and preliminary findings. Ann Acad Med Singapore 2006; 35: 783-9.
17. Paradkar PN, Ooi EE, Hanson BJ, Gubler DJ, Vasudevan SG. Unfolded protein response (UPR) gene expression during antibody-dependent enhanced infection of cultured monocytes correlates with dengue disease severity. Biosci Rep 2011; 31: 221-30.
18. Moreland NJ, Tay MY, Lim E, et al. Monoclonal antibodies against dengue NS2B and NS3 proteins for the study of protein interactions in the flaviviral replication complex. J Virol Methods 2012; 179: 97-103.
19. Zhao Y, Moreland NJ, Tay MY, Lee CC, Swaminathan K, Vasudevan SG. Identification and molecular characterization of human antibody fragments specific for dengue NS5 protein. Virus Res 2014; 179: 225-30.
20. Wagstaff KM, Rawlinson SM, Hearps AC, Jans DA. An Alpha Screen® -based assay for high-throughput screening for specific inhibitors of nuclear import. J Biomol Screen 2011; 16: 192-200.
21. Kobe B. Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha. Nat Struct Biol 1999; 6: 388-97.
22. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402-8.
23. Zellweger RM, Prestwood TR, Shresta S. Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease. Cell Host Microbe 2010; 7: 128-39.
24. Rawlinson SM, Pryor MJ, Wright PJ, Jans DA. CRM1-mediated nuclear export of dengue virus RNA polymerase NS5 modulates inter-leukin-8 induction and virus production. J Biol Chem 2009; 284: 15589-97.
25. Garaventa A, Luksch R, Lo Piccolo MS, et al. Phase I trial and pharma-cokinetics of fenretinide in children with neuroblastoma. Clin Cancer Res 2003; 9: 2032-9.
26. Villablanca JG, Krailo MD, Ames MM, Reid JM, Reaman GH, Reynolds CP. Phase I trial of oral fenretinide in children with high-risk solid tumors: a report from the Children's Oncology Group (CCG 09709). J Clin Oncol 2006; 24: 3423-30.
27. Villablanca JG, London WB, Naranjo A, et al. Phase II study of oral cap-sular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: a report from the Children's Oncology Group. Clin Cancer Res 2011; 17: 6858-66.
28. Anders KL, Nguyet NM, Chau NV, et al. Epidemiological factors associated with dengue shock syndrome and mortality in hospitalized dengue patients in Ho Chi Minh City, Vietnam. Am J Trop Med Hyg 2011; 84: 127-34.
29. Fraser JE, Rawlinson SM, Wang C, Jans DA, Wagstaff KM. Investigating dengue virus non-structural protein 5 (NS5) nuclear import. In: Padmanabhan R, Vasudevan SG, ed. Dengue: methods and protocols. Vol 1138. Springer, 2014.
30. Altucci L, Leibowitz MD, Ogilvie KM, de Lera AR, Gronemeyer H. RAR and RXR modulation in cancer and metabolic disease. Nat Rev Drug Discov 2007; 6: 793-810.
31. Villani MG, Appierto V, Cavadini E, et al. Identification of the fenretinide metabolite 4-oxo-fenretinide present in human plasma and formed in human ovarian carcinoma cells through induction of cytochrome P450 26A1. Clin Cancer Res 2004; 10: 6265-75.
32. Mehta RG, Moon RC, Hawthorne M, Formelli F, Costa A. Distribution of fenretinide in the mammary gland of breast cancer patients. Eur J Cancer 1991; 27: 138-41.
33. Rahmaniyan M, Curley RW Jr, Obeid LM, Hannun YA, Kraveka JM. Identification of dihydroceramide desaturase as a direct in vitro target for fenretinide. J Biol Chem 2011; 286: 24754-64.
34. Triola G, Fabrias G, Llebaria A. Synthesis of a cyclopropene analogue of ceramide, a potent inhibitor of dihydroceramide desaturase. Angew Chem Int Ed Engl 2001; 40: 1960-2.
35. Miyake Y, Kozutsumi Y, Nakamura S, Fujita T, Kawasaki T. Serine palmitoyltransferase is the primary target of a sphingosine-like immuno-suppressant, ISP-1/myriocin. Biochem Biophys Res Commun 1995; 211: 396-403.
36. Lai WL, Wong NS. The PERK/eIF2 alpha signaling pathway of Unfolded Protein Response is essential for N-(4-hydroxyphenyl)retinamide (4HPR)-induced cytotoxicity in cancer cells. Exp Cell Res 2008; 314: 1667-82.
37. Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 2012; 13: 89-102.
38. Umareddy I, Pluquet O, Wang QY, Vasudevan SG, Chevet E, Gu F. Dengue virus serotype infection specifies the activation of the unfolded protein response. Virol J 2007; 4: 91.
39. van Huizen R, Martindale JL, Gorospe M, Holbrook NJ. P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling. J Biol Chem 2003; 278: 15558-64.
40. Thastrup O, Cullen PJ, Drobak BK, Hanley MR, Dawson AP. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Nat Acad Sci U S A 1990; 87: 2466-70.
41. Jessie K, Fong MY, Devi S, Lam SK, Wong KT. Localization of dengue virus in naturally infected human tissues, by immunohistochemistry and in situ hybridization. J Infect Dis 2004; 189: 1411-8.
42. Cooper JP, Hwang K, Singh H, et al. Fenretinide metabolism in humans and mice: utilizing pharmacological modulation of its metabolic pathway to increase systemic exposure. Br J Pharmacol 2011; 163: 1263-75.
43. Mathew A, Rothman AL. Understanding the contribution of cellular immunity to dengue disease pathogenesis. Immunol Rev 2008; 225: 300-13.
44. Sheikh MS, Shao ZM, Li XS, et al. N-(4-hydroxyphenyl)retinamide (4-HPR)-mediated biological actions involve retinoid receptor-independent pathways in human breast carcinoma. Carcinogenesis 1995; 16: 2477-86.
45. Veronesi U, Mariani L, Decensi A, et al. Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Ann Oncol 2006; 17: 1065-71.
46. Sabichi AL, Lerner SP, Atkinson EN, et al. Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer. Clin Cancer Res 2008; 14: 224-9.
47. Pena J, Harris E. Dengue virus modulates the unfolded protein response in a time-dependent manner. J Biol Chem 2011; 286: 14226-36.
48. Ambrose RL, Mackenzie JM. West Nile virus differentially modulates the unfolded protein response to facilitate replication and immune evasion. J Virol 2011; 85: 2723-32.
49. Costa VV, Fagundes CT, Souza DG, Teixeira MM. Inflammatory and innate immune responses in dengue infection: protection versus disease induction. Am J Pathol 2013; 182: 1950-61.
50. Maurer BJ, Kang MH, Villablanca JG, et al. Phase I trial of fenretinide delivered orally in a novel organized lipid complex in patients with relapsed/refractory neuroblastoma: a report from the New Approaches to Neuroblastoma Therapy (NANT) consortium. Pediatr Blood Cancer 2013; 60: 1801-8.