Rock1 is a novel host dependency factor of human enterovirus A71: Implication as a drug target.
EV-A71
Rock1
host factor
intestinal organoids
kinase inhibitors
Journal
Journal of medical virology
ISSN: 1096-9071
Titre abrégé: J Med Virol
Pays: United States
ID NLM: 7705876
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
revised:
30
06
2022
received:
28
05
2022
accepted:
01
07
2022
pubmed:
7
7
2022
medline:
15
9
2022
entrez:
6
7
2022
Statut:
ppublish
Résumé
Human enterovirus A71 (EV-A71) is the major causative agent of hand-foot-and-mouth disease (HFMD) commonly associated with severe neurological diseases, particularly in children under 5 years of age. Several investigational therapeutic agents and vaccine candidates are being developed. However, no approved drug against EV-A71 infection is available, and no proven drug target has been identified. Since host kinases are key regulators of multiple signaling pathways in response to viral infections, here we screened a kinase inhibitor library and identified potent inhibitors against EV-A71 infection. Among the hits, GSK269962A, a Rho Associated Coiled-Coil Containing Protein Kinase (Rock) inhibitor with potent antiviral activity, was selected for further analysis. We found that this Rock inhibitor not only efficiently suppressed the replication of EV-A71 in RD cells, but also in human intestinal organoids, in a dose-dependent manner. Interestingly, small interfering RNA depletion of Rock1, but not Rock2, significantly restricted viral replication in RD cells, indicating that Rock1 is a novel host dependency factor for EV-A71 replication and can serve as a target for the development of anti-EV-A71 therapeutics.
Substances chimiques
Antigens, Viral
0
ROCK1 protein, human
EC 2.7.11.1
rho-Associated Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5415-5424Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
Yeung ML, Jia L, Yip C, et al. Human tryptophanyl-tRNA synthetase is an IFN-γ-inducible entry factor for enterovirus. J Clin Invest. 2018;128:5163-5177.
Shimizu H, Nakashima K. Surveillance of hand, foot, and mouth disease for a vaccine. Lancet Infect Dis. 2014;14:262-263.
Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis. 2010;10:778-790.
McMinn P, Stratov I, Nagarajan L, Davis S. Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis. 2001;32:236-242.
Wu KX, Ng MM, Chu JJ. Developments towards antiviral therapies against enterovirus 71. Drug Discov Today. 2010;15:1041-1051.
Fang C-Y, Liu C-C. Recent development of enterovirus A vaccine candidates for the prevention of hand, foot, and mouth disease. Expert Rev Vaccines. 2018;17:819-831.
Sun J, Yogarajah T, Lee RCH, et al. Drug repurposing of pyrimidine analogs as potent antiviral compounds against human enterovirus A71 infection with potential clinical applications. Sci Rep. 2020;10:1-13.
Huang P-N, Shih S-R. Update on enterovirus 71 infection. Curr Opin Virol. 2014;5:98-104.
Smyth M, Martin JH. Picornavirus uncoating. Mol Pathol. 2002;55:214-219.
Bedard KM, Semler BL. Regulation of picornavirus gene expression. Microb Infect. 2004;6:702-713.
McMinn PC. An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev. 2002;26:91-107.
Thompson SR, Sarnow P. Enterovirus 71 contains a type I IRES element that functions when eukaryotic initiation factor eIF4G is cleaved. Virology. 2003;315:259-266.
Lin J-Y, Shih S-R, Pan M, et al. hnRNP A1 interacts with the 5′ untranslated regions of enterovirus 71 and sindbis virus RNA and is required for viral replication. J Virol. 2009;83:6106-6114.
Huang PN, Lin JY, Locker N, et al. Far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth. Nucleic Acids Res. 2011;39:9633-9648.
Lin J-Y, Li M-L, Shih S-R. Far upstream element binding protein 2 interacts with enterovirus 71 internal ribosomal entry site and negatively regulates viral translation. Nucleic Acids Res. 2009;37:47-59.
Leong SY, Ong BK, Chu JJ. The role of Misshapen NCK-related kinase (MINK), a novel Ste20 family kinase, in the IRES-mediated protein translation of human enterovirus 71. PLoS Pathog. 2015;11:e1004686.
Gross S, Rahal R, Stransky N, Lengauer C, Hoeflich KP. Targeting cancer with kinase inhibitors. J Clin Invest. 2015;125:1780-1789.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646-674.
Takamatsu Y, Krähling V, Kolesnikova L, et al. Serine-arginine protein kinase 1 regulates Ebola virus transcription. mBio. 2020;11:e02565-19.
Sieczkarski SB, Brown HA, Whittaker GR. Role of protein kinase C βII in influenza virus entry via late endosomes. J Virol. 2003;77:460-469.
Wu KX, Phuektes P, Kumar P, et al. Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication. Nat Commun. 2016;7:13150.
Min N, Leong PT, Lee RCH, Khuan J, Chu J. A flavonoid compound library screen revealed potent antiviral activity of plant-derived flavonoids on human enterovirus A71 replication. Antiviral Res. 2018;150:60-68.
Blutt SE, Crawford SE, Ramani S, Zou WY, Estes MK. Engineered human gastrointestinal cultures to study the microbiome and infectious diseases. Cell Mol Gastroenterol Hepatol. 2018;5:241-251.
Wilding JL, Bodmer WF. Cancer cell lines for drug discovery and development. Cancer Res. 2014;74:2377-2384.
Gazdar AF, Gao B, Minna JD. Lung cancer cell lines: useless artifacts or invaluable tools for medical science? Lung Cancer. 2010;68:309-318.
Sato T, Stange DE, Ferrante M, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology. 2011;141:1762-1772.
Zhou J, Li C, Liu X, et al. Infection of bat and human intestinal organoids by SARS-CoV-2. Nature Med. 2020;26:1-7.
Ettayebi K, Crawford SE, Murakami K, et al. Replication of human noroviruses in stem cell-derived human enteroids. Science. 2016;353:1387-1393.
Zhao X, Li C, Liu X, et al. Human intestinal organoids recapitulate enteric infections of enterovirus and coronavirus. Stem Cell Reports. 2021;16:493-504.
Duque-Correa MA, Maizels RM, Grencis RK, Berriman M. Organoids-new models for Host-Helminth interactions. Trends Parasitol. 2020;36:170-181.
Roskoski Jr., R. Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update. Pharmacol Res. 2020;152:104609.
Zhou J, Chu H, Li C, et al. Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis. J Infect Dis. 2014;209:1331-1342.
Yuan S, Chu H, Huang J, et al. Viruses harness YxxØ motif to interact with host AP2M1 for replication: a vulnerable broad-spectrum antiviral target. Sci Adv. 2020;6:eaba7910.
Zhou J, Li C, Zhao G, et al. Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus. Sci Adv. 2017;3:eaao4966.
Zhao X, Chu H, Wong BH, et al. Activation of C-type lectin receptor and (RIG)-I-like receptors contributes to proinflammatory response in Middle East respiratory syndrome coronavirus-infected macrophages. J Infect Dis. 2020;221:647-659.
Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Epidemiol. 1938;27:493-497.
Zhou J, To KK, Dong H, et al. A functional variation in CD55 increases the severity of 2009 pandemic H1N1 influenza A virus infection. J Infect Dis. 2012;206:495-503.
Xiao X, Lei X, Zhang Z, et al. Enterovirus 3A facilitates viral replication by promoting phosphatidylinositol 4-Kinase IIIbeta-ACBD3 interaction. J Virol. 2017;91:91.
Wang B, Zhang H, Zhu M, Luo Z, Peng Y. MEK1-ERKs signal cascade is required for the replication of enterovirus 71 (EV71). Antiviral Res. 2012;93:110-117.
Chang J, Xie M, Shah VR, et al. Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis. Proc Natl Acad Sci. 2006;103:14495-14500.
Wang J-R, Tuan Y-C, Tsai H-P, Yan JJ, Liu CC, Su IJ. Change of major genotype of enterovirus 71 in outbreaks of hand-foot-and-mouth disease in Taiwan between 1998 and 2000. J Clin Microbiol. 2002;40:10-15.
Doe C, Bentley R, Behm DJ, et al. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007;320:89-98.
Riento K, Ridley AJ. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol. 2003;4:446-456.
Yoneda A, Multhaupt HA, Couchman JR. The Rho kinases I and II regulate different aspects of myosin II activity. the. J Cell Biol. 2005;170:443-453.
Shi J, Zhang L, Wei L. Rho-kinase in development and heart failure: insights from genetic models. Pediatr Cardiol. 2011;32:297-304.
Eliyahu E, Tirosh O, Dobesova M, Nachshon A, Schwartz M, Stern-Ginossar N. Rho-associated coiled-coil kinase 1 translocates to the nucleus and inhibits human cytomegalovirus propagation. J Virol. 2019;93:93.