DOI QR코드

DOI QR Code

Antiviral and Anti-Inflammatory Activities of Pochonin D, a Heat Shock Protein 90 Inhibitor, against Rhinovirus Infection

  • Received : 2017.11.23
  • Accepted : 2018.02.01
  • Published : 2018.11.01

Abstract

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.

Keywords

References

  1. Ahn, E. K., Yoon, H. K., Jee, B. K., Ko, H. J., Lee, K. H., Kim, H. J. and Lim, Y. (2008) COX-2 expression and inflammatory effects by diesel exhaust particles in vitro and in vivo. Toxicol. Lett. 176, 178-187. https://doi.org/10.1016/j.toxlet.2007.11.005
  2. al-Nakib, W. and Tyrrell, D. A. (1992) Drugs against rhinoviruses. J. Antimicrob. Chemother. 30, 115-117. https://doi.org/10.1093/jac/30.2.115
  3. Atretkhany, K. N. and Drutskaya, M. S. (2016) Myeloid-derived suppressor cells and proinflammatory cytokines as targets for cancer therapy. Biochemistry Mosc. 81, 1274-1283. https://doi.org/10.1134/S0006297916110055
  4. Bartlett, N. W., Walton, R. P., Edwards, M. R., Aniscenko, J., Caramori, G., Zhu, J. et al. (2008) Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Nat. Med. 14, 199-204. https://doi.org/10.1038/nm1713
  5. Basha, W., Kitagawa, R., Uhara, M., Imazu, H., Uechi, K. and Tanaka, J. (2005) Geldanamycin, a potent and specific inhibitor of Hsp90, inhibits gene expression and replication of human cytomegalovirus. Antivir. Chem. Chemother. 16, 135-146. https://doi.org/10.1177/095632020501600206
  6. Brenner, B. G. and Wainberg, M. A. (1999) Heat shock protein-based therapeutic strategies against human immunodeficiency virus type 1 infection. Infect. Dis. Obstet. Gynecol. 7, 80-90.
  7. Burch, A. D. and Weller, S. K. (2005) Herpes simplex virus type 1 DNA polymerase requires the mammalian chaperone hsp90 for proper localization to the nucleus. J. Virol. 79, 10740-10749. https://doi.org/10.1128/JVI.79.16.10740-10749.2005
  8. Chatterjee, A., Dimitropoulou, C., Drakopanayiotakis, F., Antonova, G., Snead, C., Cannon, J., Venema, R. C. and Catravas, J. D. (2007) Heat shock protein 90 inhibitors prolong survival, attenuate inflammation, and reduce lung injury in murine sepsis. Am. J. Respir. Crit. Care Med. 176, 667-675. https://doi.org/10.1164/rccm.200702-291OC
  9. Choe, H., Cho, H., Ko, H. J. and Lee, J. (2017) Total synthesis of (+)-pochonin D and (+)-monocillin ii via chemo- and regioselective intramolecular nitrile oxide cycloaddition. Org. Lett. 19, 6004-6007. https://doi.org/10.1021/acs.orglett.7b03054
  10. Geller, R., Andino, R. and Frydman, J. (2013) Hsp90 inhibitors exhibit resistance-free antiviral activity against respiratory syncytial virus. PLoS ONE 8, e56762. https://doi.org/10.1371/journal.pone.0056762
  11. Geller, R., Taguwa, S. and Frydman, J. (2012) Broad action of Hsp90 as a host chaperone required for viral replication. Biochim. Biophys. Acta 1823, 698-706. https://doi.org/10.1016/j.bbamcr.2011.11.007
  12. Geller, R., Vignuzzi, M., Andino, R. and Frydman, J. (2007) Evolutionary constraints on chaperone-mediated folding provide an antivi-ral approach refractory to development of drug resistance. Genes Dev. 21, 195-205. https://doi.org/10.1101/gad.1505307
  13. Gern, J. E. and Busse, W. W. (1999) Association of rhinovirus infections with asthma. Clin. Microbiol. Rev. 12, 9-18. https://doi.org/10.1128/CMR.12.1.9
  14. Hellwig, V., Mayer-Bartschmid, A., Muller, H., Greif, G., Kleymann, G., Zitzmann, W., Tichy, H. V. and Stadler, M. (2003) Pochonins A-F, new antiviral and antiparasitic resorcylic acid lactones from Pochonia chlamydosporia var. catenulata. J. Nat. Prod. 66, 829-837. https://doi.org/10.1021/np020556v
  15. Hsu, H. Y., Wu, H. L., Tan, S. K., Li, V. P., Wang, W. T., Hsu, J. and Cheng, C. H. (2007) Geldanamycin interferes with the 90-kDa heat shock protein, affecting lipopolysaccharide-mediated interleukin-1 expression and apoptosis within macrophages. Mol. Pharmacol. 71, 344-356. https://doi.org/10.1124/mol.106.024240
  16. Jartti, T. and Korppi, M. (2011) Rhinovirus-induced bronchiolitis and asthma development. Pediatr. Allergy Immunol. 22, 350-355. https://doi.org/10.1111/j.1399-3038.2011.01170.x
  17. Jeisy-Scott, V., Davis, W. G., Patel, J. R., Bowzard, J. B., Shieh, W. J., Zaki, S. R., Katz, J. M. and Sambhara, S. (2011) Increased MDSC accumulation and Th2 biased response to influenza A virus infection in the absence of TLR7 in mice. PLoS ONE 6, e25242. https://doi.org/10.1371/journal.pone.0025242
  18. Kampmueller, K. M. and Miller, D. J. (2005) The cellular chaperone heat shock protein 90 facilitates Flock House virus RNA replication in Drosophila cells. J. Virol. 79, 6827-6837. https://doi.org/10.1128/JVI.79.11.6827-6837.2005
  19. Kneyber, M. C., Moll, H. A. and de Groot, R. (2000) Treatment and prevention of respiratory syncytial virus infection. Eur. J. Pediatr. 159, 399-411. https://doi.org/10.1007/s004310051296
  20. Ledford, R. M., Collett, M. S. and Pevear, D. C. (2005) Insights into the genetic basis for natural phenotypic resistance of human rhinoviruses to pleconaril. Antiviral Res. 68, 135-138. https://doi.org/10.1016/j.antiviral.2005.08.003
  21. Li, Y., Zhang, T., Schwartz, S. J. and Sun, D. (2009) New developments in Hsp90 inhibitors as anti-cancer therapeutics: mechanisms, clinical perspective and more potential. Drug Resist. Updat. 12, 17-27. https://doi.org/10.1016/j.drup.2008.12.002
  22. Li, Y. H., Tao, P. Z., Liu, Y. Z. and Jiang, J. D. (2004) Geldanamycin, a ligand of heat shock protein 90, inhibits the replication of herpes simplex virus type 1 in vitro. Antimicrob. Agents Chemother. 48, 867-872. https://doi.org/10.1128/AAC.48.3.867-872.2004
  23. Liebhart, J., Cembrzynska-Nowak, M., Bienkowska, M., Liebhart, E., Dobek, R., Zaczynska, E., Panaszek, B., Obojski, A. and Malolepszy, J. (2002) Relevance of the selected cytokine release (TNF-alpha, IL-6, IFN-gamma, and IFN-alpha) to the exacerbation of bronchial asthma from airway mycotic infections. Predominant role of TFN-alpha? J. Investig. Allergol. Clin. Immunol. 12, 182-191.
  24. Molinos-Quintana, A., Perez-de Soto, C., Gomez-Rosa, M., Perez-Simon, J. A. and Perez-Hurtado, J. M. (2013) Intravenous ribavirin for respiratory syncytial viral infections in pediatric hematopoietic SCT recipients. Bone Marrow Transplant. 48, 265-268. https://doi.org/10.1038/bmt.2012.134
  25. Momose, F., Naito, T., Yano, K., Sugimoto, S., Morikawa, Y. and Nagata, K. (2002) Identification of Hsp90 as a stimulatory host factor involved in influenza virus RNA synthesis. J. Biol. Chem. 277, 45306-45314. https://doi.org/10.1074/jbc.M206822200
  26. Moulin, E., Zoete, V., Barluenga, S., Karplus, M. and Winssinger, N. (2005) Design, synthesis, and biological evaluation of HSP90 inhibitors based on conformational analysis of radicicol and its analogues. J. Am. Chem. Soc. 127, 6999-7004. https://doi.org/10.1021/ja043101w
  27. Nagy, P. D., Wang, R. Y., Pogany, J., Hafren, A. and Makinen, K. (2011) Emerging picture of host chaperone and cyclophilin roles in RNA virus replication. Virology 411, 374-382. https://doi.org/10.1016/j.virol.2010.12.061
  28. Nakagawa, S., Umehara, T., Matsuda, C., Kuge, S., Sudoh, M. and Kohara, M. (2007) Hsp90 inhibitors suppress HCV replication in replicon cells and humanized liver mice. Biochem. Biophys. Res. Commun. 353, 882-888. https://doi.org/10.1016/j.bbrc.2006.12.117
  29. Neckers, L. and Workman, P. (2012) Hsp90 molecular chaperone inhibitors: are we there yet? Clin. Cancer Res. 18, 64-76. https://doi.org/10.1158/1078-0432.CCR-11-1000
  30. Park, S. H., Song, J. H., Kim, T., Shin, W. S., Park, G. M., Lee, S., Kim, Y. J., Choi, P., Kim, H., Kim, H. S., Kwon, D. H., Choi, H. J. and Ham, J. (2012) Anti-human rhinoviral activity of polybromocatechol compounds isolated from the rhodophyta, Neorhodomela aculeata. Mar. Drugs 10, 2222-2233. https://doi.org/10.3390/md10102222
  31. Rincon, M. and Irvin, C. G. (2012) Role of IL-6 in asthma and other inflammatory pulmonary diseases. Int. J. Biol. Sci. 8, 1281-1290. https://doi.org/10.7150/ijbs.4874
  32. Roe, S. M., Prodromou, C., O'Brien, R., Ladbury, J. E., Piper, P. W. and Pearl, L. H. (1999) Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J. Med. Chem. 42, 260-266. https://doi.org/10.1021/jm980403y
  33. Saklatvala, J., Rawlinson, L., Waller, R. J., Sarsfield, S., Lee, J. C., Morton, L. F., Barnes, M. J. and Farndale, R. W. (1996) Role for p38 mitogen-activated protein kinase in platelet aggregation caused by collagen or a thromboxane analogue. J. Biol. Chem. 271, 6586-6589. https://doi.org/10.1074/jbc.271.12.6586
  34. Seo, S. U., Kwon, H. J., Ko, H. J., Byun, Y. H., Seong, B. L., Uematsu, S., Akira, S. and Kweon, M. N. (2011) Type I interferon signaling regulates Ly6C(hi) monocytes and neutrophils during acute viral pneumonia in mice. PLoS Pathog. 7, e1001304. https://doi.org/10.1371/journal.ppat.1001304
  35. Seo, S. U., Kwon, H. J., Song, J. H., Byun, Y. H., Seong, B. L., Kawai, T., Akira, S. and Kweon, M. N. (2010) MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection. J. Virol. 84, 12713-12722. https://doi.org/10.1128/JVI.01675-10
  36. Shi, L., Xiong, H., He, J., Deng, H., Li, Q., Zhong, Q., Hou, W., Cheng, L., Xiao, H. and Yang, Z. (2007) Antiviral activity of arbidol against influenza A virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo. Arch. Virol. 152, 1447-1455. https://doi.org/10.1007/s00705-007-0974-5
  37. Smith, D. R., McCarthy, S., Chrovian, A., Olinger, G., Stossel, A., Geisbert, T. W., Hensley, L. E. and Connor, J. H. (2010) Inhibition of heat-shock protein 90 reduces Ebola virus replication. Antiviral Res. 87, 187-194. https://doi.org/10.1016/j.antiviral.2010.04.015
  38. Song, J. H., Park, K. S., Kwon, D. H. and Choi, H. J. (2013) Anti-human rhinovirus 2 activity and mode of action of quercetin-7-glucoside from Lagerstroemia speciosa. J. Med. Food 16, 274-279. https://doi.org/10.1089/jmf.2012.2290
  39. Song, J., Yeo, S. G., Hong, E. H., Lee, B. R., Kim, J. W., Kim, J., Jeong, H., Kwon, Y., Kim, H., Lee, S., Park, J. H. and Ko, H. J. (2014) Antiviral activity of hederasaponin b from hedera helix against enterovirus 71 subgenotypes C3 and C4a. Biomol. Ther. (Seoul) 22, 41-46. https://doi.org/10.4062/biomolther.2013.108
  40. Subauste, M. C., Jacoby, D. B., Richards, S. M. and Proud, D. (1995) Infection of a human respiratory epithelial cell line with rhinovirus. Induction of cytokine release and modulation of susceptibility to infection by cytokine exposure. J. Clin. Invest. 96, 549-557. https://doi.org/10.1172/JCI118067
  41. Sun, X., Bristol, J. A., Iwahori, S., Hagemeier, S. R., Meng, Q., Barlow, E. A., Fingeroth, J. D., Tarakanova, V. L., Kalejta, R. F. and Kenney, S. C. (2013) Hsp90 inhibitor 17-DMAG decreases expression of conserved herpesvirus protein kinases and reduces virus production in Epstein-Barr virus-infected cells. J. Virol. 87, 10126-10138. https://doi.org/10.1128/JVI.01671-13
  42. Wang, M., Shen, A., Zhang, C., Song, Z., Ai, J., Liu, H., Sun, L., Ding, J., Geng, M. and Zhang, A. (2016) Development of Heat Shock Protein (Hsp90) Inhibitors To Combat Resistance to Tyrosine Kinase Inhibitors through Hsp90-Kinase Interactions. J. Med. Chem. 59, 5563-5586. https://doi.org/10.1021/acs.jmedchem.5b01106
  43. Zaheer, R. S., Wiehler, S., Hudy, M. H., Traves, S. L., Pelikan, J. B., Leigh, R. and Proud, D. (2014) Human rhinovirus-induced ISG15 selectively modulates epithelial antiviral immunity. Mucosal Immunol. 7, 1127-1138. https://doi.org/10.1038/mi.2013.128
  44. Zhou, H., Qiao, K., Gao, Z., Vederas, J. C. and Tang, Y. (2010) Insights into radicicol biosynthesis via heterologous synthesis of intermediates and analogs. J. Biol. Chem. 285, 41412-41421. https://doi.org/10.1074/jbc.M110.183574
  45. Zur Wiesch, P. A., Kouyos, R., Engelstadter, J., Regoes, R. R. and Bonhoeffer, S. (2011) Population biological principles of drug-resistance evolution in infectious diseases. Lancet Infect. Dis. 11, 236-247. https://doi.org/10.1016/S1473-3099(10)70264-4

Cited by

  1. Anti-Human Rhinovirus 1B Activity of Dexamethasone viaGCR-Dependent Autophagy Activation vol.9, pp.6, 2018, https://doi.org/10.24171/j.phrp.2018.9.6.07
  2. IκBζ facilitates protective immunity against Salmonella infection via Th1 differentiation and IgG production vol.9, pp.None, 2018, https://doi.org/10.1038/s41598-019-44019-3
  3. A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity vol.29, pp.2, 2021, https://doi.org/10.4062/biomolther.2020.131
  4. Rhinovirus Inhibitors: Including a New Target, the Viral RNA vol.13, pp.9, 2018, https://doi.org/10.3390/v13091784