Shedding light on filovirus infection with high-content imaging

Viruses

Volumn 4, Issue 8, 2012, Pages 1354-1371

  Panchal, Rekha G ^a   Pegoraro, Gianluca ^a,b   Bavari, Sina ^a  

^a UNITED STATES ARMY MEDICAL RESEARCH INSTITUTE OF INFECTIOUS DISEASES   (United States)

^b PERKINELMER INC   (United States)

Author keywords

Filoviruses; High content imaging; Host pathogen interactions; Phenotype; Therapeutics

Indexed keywords

ANTIOXIDANT; ANTIVIRUS AGENT; NSC 62914; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; AUTOANALYSIS; COMPUTER PROGRAM; DRUG SCREENING; EBOLA HEMORRHAGIC FEVER; EBOLA VIRUS; EQUIPMENT DESIGN; FILOVIRUS INFECTION; FLUORESCENCE MICROSCOPY; GENETIC SCREENING; GENOME ANALYSIS; HIGH CONTENT IMAGING; HIGH THROUGHPUT SCREENING; HUMAN; IMAGE ANALYSIS; MARBURG VIRUS; MOLECULAR IMAGING; NONHUMAN; QUANTITATIVE ANALYSIS; REVIEW; SINGLE CELL ANALYSIS; VIRUS ATTACHMENT; VIRUS CELL INTERACTION; VIRUS CULTURE; VIRUS ENTRY; VIRUS EXAMINATION; VIRUS REPLICATION;

FILOVIRUSES; HIGH-CONTENT IMAGING; HOST-PATHOGEN INTERACTIONS; PHENOTYPE; THERAPEUTICS;

ANIMALS; FILOVIRIDAE; FILOVIRIDAE INFECTIONS; HIGH-THROUGHPUT SCREENING ASSAYS; HOST-PATHOGEN INTERACTIONS; HUMANS; MICROSCOPY;

EID: 84865401636     PISSN: 19994915     EISSN: None     Source Type: Journal    
DOI: 10.3390/v4081354     Document Type: Review

References (107)

1. Conrad, C.; Gerlich, D.W. Automated microscopy for high-content RNAi screening. J. Cell Biol. 2010, 188, 453-461
2. Ljosa, V.; Carpenter, A.E. Introduction to the quantitative analysis of two-dimensional fluorescence microscopy images for cell-based screening. PLoS Comput. Biol. 2009, 5, e 1000603
3. Danovi, D.; Falk, A.; Humphreys, P.; Vickers, R.; Tinsley, J.; Smith, A.G.; Pollard, S.M. Imaging-based chemical screens using normal and glioma-derived neural stem cells. Biochem. Soc. Trans. 2010, 38, 1067-1071
4. O'Brien, P.J.; Irwin, W.; Diaz, D.; Howard-Cofield, E.; Krejsa, C.M.; Slaughter, M.R.; Gao, B.; Kaludercic, N.; Angeline, A.; Bernardi, P.; Brain, P.; Hougham, C. High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high content screening. Arch. Toxicol. 2006, 80, 580-604
5. Götte, M.; Hofmann, G.; Michou-Gallani, A.-I.; Glickman, J.F.; Wishart, W.; Gabriel, D. An imaging assay to analyze primary neurons for cellular neurotoxicity. I Neurosci. Methods 2010, 192, 7-16
6. Kredel, S.; Wolff, M.; Hobbie, S.; Bieler, M.; Gierschik, P.; Heilker, R. High-content analysis of CCR2 antagonists on human primary monocytes. J. Biomol. Screen. 2011, 16, 683-693.
7. Brodin, P.; Christophe, T. High-content screening in infectious diseases. Curr. Opin. Chem. Biol. 2011, 15, 534-539.
8. Daub, A.; Sharma, P.; Finkbeiner, S. High-content screening of primary neurons: Ready for prime time. Curr. Opin. Neurobiol. 2009, 19, 537-543.
9. Borio, L.; Inglesby, T.; Peters, C.J.; Schmaljohn, A.L.; Hughes, J.M.; Jahrling, P.B.; Ksiazek, T.; Johnson, K.M.; Meyerhoff, A.; O'Toole, T.;et al. Hemorrhagic fever viruses as biological weapons: Medical and public health management. I Am. Med. Assoc. 2002, 287, 2391-2405.
10. Schnittler, H.J.; Feldmann, H. Molecular pathogenesis of filovirus infections: Role of macrophages and endothelial cells. Curr. Top. Microbiol. Immunol. 1999, 235, 175-204.
11. Falzarano, D.; Geisbert, T.W.; Feldmann, H. Progress in filovirus vaccine development: Evaluating the potential for clinical use. Expert. Rev. Vaccines 2011, 10, 63-77.
12. Grant-Klein, R.J.; Altamura, L.A.; Schmaljohn, C.S. Progress in recombinant DNA-derived vaccines for Lassa virus and filoviruses. Virus Res. 2011, 162, 148-161.
13. Warfield, K.L.; Aman, M.J. Advances in virus-like particle vaccines for filoviruses. I Infect. Dis. 2011, 204, S1053-S1059.
14. Warren, T.K.; Warfield, K.L.; Wells, J.; Swenson, D.L.; Donner, K.S.; Van Tongeren, S.A.; Garza, N.L.; Dong, L.; Mourich, D.V.; Crumley, S.; et al. Advanced antisense therapies for postexposure protection against lethal filovirus infections. Nat. Med. 2010, 16, 991-994.
15. Warren, T.K.; Shurtleff, A.C.; Bavari, S. Advanced morpholino oligomers: A novel approach to antiviral therapy. Antivir. Res. 2012, 94, 80-88.
16. Mahanty, S.; Bray, M. Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect. Dis. 2004, 4, 487-498.
17. Leroy, E.M.; Kumulungui, B.; Pourrut, X.; Rouquet, P.; Hassanin, A.; Yaba, P.; Délicat, A.; Paweska, J.T.; Gonzalez, J.-P.; Swanepoel, R. Fruit bats as reservoirs of Ebola virus. Nature 2005, 438, 575-576.
18. Towner, J.S.; Amman, B.R.; Sealy, T.K.; Carroll, S.A.R.; Comer, J.A.; Kemp, A.; Swanepoel, R.; Paddock, C.D.; Balinandi, S.; Khristova, M.L.; et al. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog. 2009, 5, e 1000536.
19. Adams, M.J.; Carstens, E.B. Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2012). Arch. Virol. 2012, 157, 1411-1422.
20. Kuhn, J.H.; Becker, S.; Ebihara, H.; Geisbert, T.W.; Jahrling, P.B.; Kawaoka, Y.; Netesov, S.V.; Nichol, S.T.; Peters, C.J.; Volchkov, V.E.;et al. Family Filoviridae. In Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses; King, A.M.Q., Adams, M.J., Carstens, E.B., Lefkowitz, E.J., Eds.; Elsevier/Academic Press: London, UK, 2011; pp. 665-671.
21. Kuhn, J.H.; Becker, S.; Ebihara, H.; Geisbert, T.W.; Johnson, K.M.; Kawaoka, Y.; Lipkin, W.I.; Negredo, A.I.; Netesov, S.V.; Nichol, S.T.; et al. Proposal for a revised taxonomy of the family Filoviridae: Classification, names of taxa and viruses, and virus abbreviations. Arch. Virol. 2010, 155, 2083-2103.
22. Feldmann, H.; Müühlberger, E.; Randolf, A.; Will, C.; Kiley, M.P.; Sanchez, A.; Klenk, H.D. Marburg virus, a filovirus: Messenger RNAs, gene order, and regulatory elements of the replication cycle. Virus Res. 1992, 24, 1-19.
23. Sanchez, A.; Kiley, M.P.; Klenk, H.D.; Feldmann, H. Sequence analysis of the Marburg virus nucleoprotein gene: Comparison to Ebola virus and other non-segmented negative-strand RNA viruses. J. Gen. Virol. 1992, 73, 347-357.
24. Sanchez, A.; Kiley, M.P.; Holloway, B.P.; Auperin, D.D. Sequence analysis of the Ebola virus genome: Organization, genetic elements, and comparison with the genome of Marburg virus. Virus Res. 1993, 29, 215-240.
25. Hartlieb, B.; Weissenhorn, W. Filovirus assembly and budding. Virology 2006, 344, 64-70.
26. Morita, E.; Sundquist, W.I. Retrovirus budding. Annu. Rev. Cell Dev. Biol. 2004, 20, 395-425.
27. Schmitt, A.P.; Lamb, R.A. Escaping from the cell: Assembly and budding of negative-strand RNA viruses. Curr. Top. Microbiol. Immunol. 2004, 283, 145-196.
28. Dolnik, O.; Kolesnikova, L.; Becker, S. Filoviruses: Interactions with the host cell. Cell. Mol. Life Sci. 2008, 65, 756-776.
29. Chan, S.Y.; Empig, C.J.; Welte, F.J.; Speck, R.F.; Schmaljohn, A.; Kreisberg, J.F.; Goldsmith, M.A. Folate receptor-alpha is a cofactor for cellular entry by Marburg and Ebola viruses. Cell 2001, 106, 117-126.
30. Mohamadzadeh, M.; Chen, L.; Schmaljohn, A.L. How Ebola and Marburg viruses battle the immune system. Nat. Rev. Immunol. 2007, 7, 556-567.
31. Simmons, G.; Reeves, J.D.; Grogan, C.C.; Vandenberghe, L.H.; Baribaud, F.; Whitbeck, J.C.; Burke, E.; Buchmeier, M.J.; Soilleux, E.J.; Riley, J.L et al. DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology 2003, 305, 115-123.
32. Aleksandrowicz, P.; Marzi, A.; Biedenkopf, N.; Beimforde, N.; Becker, S.; Hoenen, T.; Feldmann, H.; Schnittler, H.-J. Ebola virus enters host cells by macropinocytosis and clathrin-mediated endocytosis. J. Infect. Dis. 2011, 204, S957-S967.
33. Sieczkarski, S.B.; Whittaker, G.R. Dissecting virus entry via endocytosis. I Gen. Virol. 2002, 83, 1535-1545.
34. Carette, J.E.; Raaben, M.; Wong, A.C.; Herbert, A.S.; Obernosterer, G.; Mulherkar, N.; Kuehne, A.I.; Kranzusch, P.J.; Griffin, A.M.; Ruthel, G.; et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 2011, 477, 340-343.
35. Chandran, K.; Sullivan, N.J.; Felbor, U.; Whelan, S.P.; Cunningham, J.M. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science 2005, 308, 1643-1645.
36. Cote, M.; Misasi, J.; Ren, T.; Bruchez, A.; Lee, K.; Filone, C.M.; Hensley, L.; Li, Q.; Ory, D.; Chandran, K.; Cunningham, J. Small molecule inhibitors reveal Niemann-Pick Cl is essential for Ebola virus infection. Nature 2011, 477, 344-348.
37. Miller, E.H.; Obernosterer, G.; Raaben, M.; Herbert, A.S.; Deffieu, M.S.; Krishnan, A.; Ndungo, E.; Sandesara, R.G.; Carette, J.E.; Kuehne, A.I.; et al. Ebola virus entry requires the host-programmed recognition of an intracellular receptor. EMBO J. 2012, 31, 1947-1960.
38. Schornberg, K.; Matsuyama, S.; Kabsch, K.; Delos, S.; Bouton, A.; White, J. Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein. I Virol. 2006, 80, 4174-4178.
39. Licata, J.M.; Simpson-Holley, M.; Wright, N.T.; Han, Z.; Paragas, J.; Harty, R.N. Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: Involvement of host proteins TSG101 and VPS-4. I Virol. 2003, 77, 1812-1819.
40. Martin-Serrano, J.; Zang, T.; Bieniasz, P.D. HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nat. Med. 2001, 7, 1313-1319.
41. Silvestri, L.S.; Ruthel, G.; Kallstrom, G.; Warfield, K.L.; Swenson, D.L.; Nelle, T.; Iversen, P.L.; Bavari, S.; Aman, M.J. Involvement of vacuolar protein sorting pathway in Ebola virus release independent of TSG101 interaction. J. Infect. Dis. 2007, 196, S264-S270.
42. Timmins, J.; Schoehn, G.; Ricard-Blum, S.; Scianimanico, S.; Vernet, T.; Ruigrok, R.W.H.; Weissenhorn, W. Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4. I Mol. Biol. 2003, 326, 493-502.
43. Urata, S.; Noda, T.; Kawaoka, Y.; Morikawa, S.; Yokosawa, H.; Yasuda, J. Interaction of Tsg101 with Marburg virus VP40 depends on the PPPY motif, but not the PT/SAP motif as in the case of Ebola virus, and Tsg101 plays a critical role in the budding of Marburg virus-like particles induced by VP40, NP, and GP. I Virol. 2007, 81, 4895-4899.
44. Liu, Y.; Harty, R.N. Viral and host proteins that modulate filovirus budding. Future Virol. 2010, 5, 481-491.
45. Basler, C.F.; Mikulasova, A.; Martinez-Sobrido, L.; Paragas, J.; Mü hlberger, E.; Bray, M.; Klenk, H.-D.; Palese, P.; García-Sastre, A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J. Virol. 2003, 77, 7945-7956.
46. Basler, C.F.; Wang, X.; Müühlberger, E.; Volchkov, V.; Paragas, J.; Klenk, H.D.; Garcia-Sastre, A.; Palese, P. The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc. Natl. Acad. Sci. U. S. A. 2000, 97, 12289-12294.
47. Ramanan, P.; Shabman, R.S.; Brown, C.S.; Amarasinghe, G.K.; Basler, C.F.; Leung, D.W. Filoviral immune evasion mechanisms. Viruses 2011, 3, 1634-1649.
48. Bickle, M. The beautiful cell: High-content screening in drug discovery. Anal. Bioanal. Chem. 2010, 398, 219-226.
49. Kozak, K.; Bakos, G.; Hoff, A.; Bennett, E.; Dunican, D.; Davies, A.; Kelleher, D.; Long, A.; Csucs, G. Workflow-based software environment for large-scale biological experiments. I Biomol. Screen. 2010, 15, 892-899.
50. Giepmans, B.N.G.; Adams, S.R.; Ellisman, M.H.; Tsien, R.Y. The fluorescent toolbox for assessing protein location and function. Science 2006, 312, 217-224.
51. Giuliano, K.A. Optimizing the integration of immunoreagents and fluorescent probes for multiplexed high content screening assays. Methods Mol. Biol. 2007, 356, 189-193.
52. Shariff, A.; Kangas, J.; Coelho, L.P.; Quinn, S.; Murphy, R.F. Automated image analysis for high-content screening and analysis. J. Biomol. Screen. 2010, 15, 726-734.
53. Maiuri, P.; Knezevich, A.; De Marco, A.; Mazza, D.; Kula, A.; McNally, J.G.; Marcello, A. Fast transcription rates of RNA polymerase II in human cells. EMBO Rep. 2011, 12, 1280-1285.
54. Maiuri, P.; Knezevich, A.; Bertrand, E.; Marcello, A. Real-time imaging of the HIV-1 transcription cycle in single living cells. Methods 2011, 53, 62-67.
55. Miorin, L.; Maiuri, P.; Hoenninger, V.M.; Mandl, C.W.; Marcello, A. Spatial and temporal organization of tick-borne encephalitis flavivirus replicated RNA in living cells. Virology 2008, 379, 64-77.
56. Rabal, O.; Link, W.; G Serelde, B.; Bischoff, J.R.; Oyarzabal, J. An integrated one-step system to extract, analyze and annotate all relevant information from image-based cell screening of chemical libraries. Mol. BioSyst. 2010, 6, 711.
57. Kummel, A.; Selzer, P.; Beibel, M.; Gubler, H.; Parker, C.N.; Gabriel, D. Comparison of multivariate data analysis strategies for high-content screening. J. Biomol. Screen. 2011, 16, 338-347.
58. Held, M.; Schmitz, M.H.A.; Fischer, B.; Walter, T.; Neumann, B.; Olma, M.H.; Peter, M.; Ellenberg, J.; Gerlich, D.W. CellCognition: Time-resolved phenotype annotation in high-throughput live cell imaging. Nat. Methods 2010, 7, 747-754.
59. Ramo, P.; Sacher, R.; Snijder, B.; Begemann, B.; Pelkmans, L. CellClassifier: Supervised learning of cellular phenotypes. Bioinformatics 2009, 25, 3028-3030.
60. Jones, T.R.; Carpenter, A.E.; Lamprecht, M.R.; Moffat, J.; Silver, S.J.; Grenier, J.K.; Castoreno, A.B.; Eggert, U.S.; Root, D.E.; Golland, P et al. Scoring diverse cellular morphologies in image-based screens with iterative feedback and machine learning. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 1826-1831.
61. Loo, L.-H.; Wu, L.F.; Altschuler, S.J. Image-based multivariate profiling of drug responses from single cells. Nat. Methods 2007, 4, 445-453.
62. Loo, L.-H.; Lin, H.-J.; Steininger, R.J.; Wang, Y.; Wu, L.F.; Altschuler, S.J. An approach for extensibly profiling the molecular states of cellular subpopulations. Nat. Methods 2009, 6, 759-765.
63. Young, D.W.; Bender, A.; Hoyt, J.; McWhinnie, E.; Chirn, G.-W.; Tao, C.Y.; Tallarico, J.A.; Labow, M.; Jenkins, J.L.; Mitchison, T.J et al. Integrating high-content screening and ligand-target prediction to identify mechanism of action. Nat. Chem. Biol. 2007, 4, 59-68.
64. Huen, M.S.Y.; Grant, R.; Manke, I.; Minn, K.; Yu, X.; Yaffe, M.B.; Chen, J. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 2007, 131, 901-914.
65. Doil, C.; Mailand, N.; Bekker-Jensen, S.; Menard, P.; Larsen, D.H.; Pepperkok, R.; Ellenberg, J.; Panier, S.; Durocher, D.; Bartek, J.; et al. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell 2009, 136, 435-446.
66. Piwko, W.; Olma, M.H.; Held, M.; Bianco, J.N.; Pedrioli, P.G.A.; Hofmann, K.; Pasero, P.; Gerlich, D.W.; Peter, M. RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. EMBO J2010, 29, 4210-4222.
67. Neumann, B.; Walter, T.; Hériché, J.-K.; Bulkescher, J.; Erfle, H.;Conrad, C.; Rogers, P.; Poser, I.; Held, M.; Liebel, U.; et al. Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. Nature 2010, 464, 721-727.
68. Moore, M.J.; Wang, Q.; Kennedy, C.J.; Silver, P.A. An alternative splicing network links cell-cycle control to apoptosis. Cell 2010, 142, 625-636.
69. Orvedahl, A.; Sumpter, R., Jr.; Xiao, G.; Ng, A.; Zou, Z.; Tang, Y.; Narimatsu, M.; Gilpin, C.; Sun, Q.; Roth, M.; et al. Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature 2011, 480, 113-117.
70. Collinet, C.; Stöter, M.; Bradshaw, C.R.; Samusik, N.;Rink, J.C.; Kenski, D.; Habermann, B Buchholz, F.; Henschel, R.; Mueller, M.S.; et al. Systems survey of endocytosis by multiparametric image analysis. Nature 2010, 464, 243-249.
71. Schwegmann, A.; Brombacher, F. Host-directed drug targeting of factors hijacked by pathogens. Sci. Signal 2008, 1, re8.
72. Zhou, H.; Xu, M.; Huang, Q.; Gates, A.T.; Zhang, X.D.; Castle, J.C.; Stec, E.; Ferrer, M.; Strulovici, B.; Hazuda, D.J.; et al. Genome-scale RNAi screen for host factors required for HIV replication. Cell Host Microbe 2008, 4, 495-504.
73. Brass, A.L.; Dykxhoorn, D.M.; Benita, Y.; Yan, N.; Engelman, A.; Xavier, R.J.; Lieberman, J.; Elledge, S.J. Identification of host proteins required for HIV infection through a functional genomic screen. Science 2008, 319, 921-926.
74. Krishnan, M.N.; Ng, A.; Sukumaran, B.; Gilfoy, F.D.; Uchil, P.D.; Sultana, H.; Brass, A.L.; Adametz, R.; Tsui, M.; Qian, F.; et al. RNA interference screen for human genes associated with West Nile virus infection. Nature 2008, 455, 242-245.
75. Li, Q.; Brass, A.L.; Ng, A.; Hu, Z.; Xavier, R.J.; Liang, T.J.; Elledge, S.J. A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 16410-16415.
76. Karlas, A.; Machuy, N.; Shin, Y.; Pleissner, K.-P.; Artarini, A.; Heuer, D.; Becker, D.; Khalil, H.; Ogilvie, L.A.; Hess, S.; et al. Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 2010, 463, 818-822.
77. Brass, A.L.; Huang, I.-C.; Benita, Y.; John, S.P.; Krishnan, M.N.; Feeley, E.M.; Ryan, B.J.; Weyer, J.L.; van der Weyden, L.; Fikrig, E.; et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 2009, 139, 1243-1254.
78. Tai, A.W.; Benita, Y.; Peng, L.F.; Kim, S.-S.; Sakamoto, N.; Xavier, R.J.; Chung, R.T. A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Cell Host Microbe 2009, 5, 298-307.
79. Ideker, T.; Goff, S.; Krogan, N. Host cell factors in HIV replication: Meta-analysis of genome-wide studies. PLoS Pathog. 2009, 5, e 1000437.
80. Birmingham, A.; Anderson, E.M.; Reynolds, A.; Ilsley-Tyree, D.; Leake, D.; Fedorov, Y.; Baskerville, S.; Maksimova, E.; Robinson, K.; Karpilow, J.; Marshall, W.S.; Khvorova, A. 3' UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 2006, 3, 199-204.
81. Snijder, B.; Sacher, R.; Ramo, P.; Damm, E.-M.; Liberali, P.; Pelkmans, L. Population context determines cell-to-cell variability in endocytosis and virus infection. Nature 2009, 461, 520-523.
82. Snijder, B.; Pelkmans, L. Origins of regulated cell-to-cell variability. Nat. Rev. Mol. Cell Biol. 2011, 12, 119-125.
83. Altschuler, S.J.; Wu, L.F. Cellular heterogeneity: Do differences make a difference? Cell 2010, 141, 559-563.
84. Knapp, B.; Rebhan, I.; Kumar, A.; Matula, P.; Kiani, N.A.; Binder, M.; Erfle, H.; Rohr, K.; Eils, R.; Bartenschlager, R.; et al. Normalizing for individual cell population context in the analysis of high-content cellular screens. BMC Bioinformatics 2011, 12, 485.
85. Snijder, B.; Sacher, R.; Ramo, P.; Liberali, P.; Mench, K.; Wolfrum, N.; Burleigh, L.; Scott, C.C.; Verheije, M.H.; Mercer, J.; et al. Single-cell analysis of population context advances RNAi screening at multiple levels. Mol. Syst. Biol. 2012, 8, 579.
86. Berke, J.M.; Fenistein, D.; Pauwels, F.; Bobbaers, R.; Lenz, O.; Lin, T.-I.; Krausz, E.; Fanning, G. Development of a high-content screening assay to identify compounds interfering with the formation of the hepatitis C virus replication complex. I Virol. Methods 2010, 165, 268-276.
87. Shum, D.; Smith, J.L.; Hirsch, J.A.; Bhinder, B.; Radu, C.; Stein, D.A.; Nelson, J.A.; Früüh, K.; Djaballah, H. High-content assay to identify inhibitors of dengue virus infection. Assay Drug Dev. Technol. 2010, 8, 553.
88. Friedrich, B.M.; Scully, C.E.; Brannan, J.M.; Ogg, M.M.; Johnston, S.C.; Hensley, L.E.; Olinger, G.G.; Smith, D.R. Assessment of High-Throughput Screening (HTS) methods for high-consequence pathogens. I Bioterr. Biodef 2011, S3, doi:10.4172/2157-2526.S3-005
89. Moe, J.B.; Lambert, R.D.; Lupton, H.W. Plaque assay for Ebola virus. I Clin. Microbiol. 1981, 13, 791-793.
90. Drosten, C.; Göttig, S.; Schilling, S.; Asper, M.; Panning, M.; Schmitz, H.; Gunther, S. Rapid detection and quantification of RNA of Ebola and Marburg viruses, Lassa virus, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription-PCR. J. Clin. Microbiol. 2002, 40, 2323-2330.
91. Trombley, A.R.; Wachter, L.; Garrison, J.; Buckley-Beason, V.A.; Jahrling, J.; Hensley, L.E.; Schoepp, R.J.; Norwood, D.A.; Goba, A.; Fair, J.N.;x /xetalet al/etal. Comprehensive panel of real-time TaqMan polymerase chain reaction assays for detection and absolute quantification of filoviruses, arenaviruses, and New World hantaviruses. Am. I Trop. Med. Hyg. 2010, 82, 954-960.
92. Bavari, S.; Bosio, C.M.; Wiegand, E.; Ruthel, G.; Will, A.B.; Geisbert, T.W.; Hevey, M.; Schmaljohn, C.; Schmaljohn, A.; Aman, M.J. Lipid raft microdomains: A gateway for compartmentalized trafficking of Ebola and Marburg viruses. I Exp. Med. 2002, 195, 593-602.
93. Swenson, D.L.; Warfield, K.L.; Kuehl, K.; Larsen, T.; Hevey, M.C.; Schmaljohn, A.; Bavari, S.; Aman, M.J. Generation of Marburg virus-like particles by co-expression of glycoprotein and matrix protein. FEMS Immunol. Med. Microbiol. 2004, 40, 27-31.
94. Basu, A.; Li, B.; Mills, D.M.; Panchal, R.G.; Cardinale, S.C.; Butler, M.M.; Peet, N.P.; Majgier-Baranowska, H.; Williams, J.D.; Patel, I.; et al. Identification of a small-molecule entry inhibitor for filoviruses. I Virol. 2011, 85, 3106-3119.
95. Basu, A.; Mills, D.M.; Bowlin, T.L. High-throughput screening of viral entry inhibitors using pseudotyped virus. Curr. Protoc. Pharmacol. 2010, Chapter 13, Unit 13B.3.
96. Hoenen, T.; Groseth, A.; de Kok-Mercado, F.; Kuhn, J.H.; Wahl-Jensen, V. Minigenomes, transcription and replication competent virus-like particles and beyond: Reverse genetics systems for filoviruses and other negative stranded hemorrhagic fever viruses. Antivir. Res. 2011, 91, 195-208.
97. Panchal, R.G.; Kota, K.P.; Spurgers, K.B.; Ruthel, G.; Tran, J.P.; Boltz, R.C.D.; Bavari, S. Development of high-content imaging assays for lethal viral pathogens. J. Biomol. Screen. 2010, 15, 755-765.
98. Panchal, R.G.; Reid, S.P.; Tran, J.P.; Bergeron, A.A.; Wells, J.; Kota, K.P.; Aman, J.; Bavari, S. Identification of an antioxidant small-molecule with broad-spectrum antiviral activity. Antivir. Res. 2012, 93, 23-29.
99. Opsenica, I.; Burnett, J.C.; Gussio, R.; Opsenica, D.; Todorović, N.; Lanteri, C.A.; Sciotti, R.J.; Gettayacamin, M.; Basilico, N.; Taramelli, D.; et al. A chemotype that inhibits three unrelated pathogenic targets: The botulinum neurotoxin serotype A light chain, P. falciparum malaria, and the Ebola filovirus. J. Med. Chem. 2011, 54, 1157-1169.
100. Spurgers, K.B.; Alefantis, T.; Peyser, B.D.; Ruthel, G.T.; Bergeron, A.A.; Costantino, J.A.; Enterlein, S.; Kota, K.P.; Boltz, R.C.D.; Aman, M.J.; et al. Identification of essential filovirion-associated host factors by serial proteomic analysis and RNAi screen. Mol. Cell Proteomics 2010, 9, 2690-2703.
101. Radoshitzky, S.R.; Dong, L.; Chi, X.; Clester, J.C.; Retterer, C.; Spurgers, K.; Kuhn, J.H.; Sandwick, S.; Ruthel, G.; Kota, K.; et al. Infectious Lassa virus, but not filoviruses, is restricted by BST-2/tetherin. J. Virol. 2010, 84, 10569-10580.
102. Radoshitzky, S.R.; Warfield, K.L.; Chi, X.; Dong, L.; Kota, K.; Bradfute, S.B.; Gearhart, J.D.; Retterer, C.; Kranzusch, P.J.; Misasi, J.N.; et al. Ebolavirus delta-peptide immunoadhesins inhibit marburgvirus and ebolavirus cell entry. I Virol. 2011, 85, 8502-8513.
103. Suratanee, A.; Rebhan, I.; Matula, P.; Kumar, A.; Kaderali, L.; Rohr, K.; Bartenschlager, R.; Eils, R.; König, R. Detecting host factors involved in virus infection by observing the clustering of infected cells in siRNA screening images. Bioinformatics 2010, 26, i653- i658.
104. Ströher, U.; West, E.; Bugany, H.; Klenk, H.D.; Schnittler, H.J.; Feldmann, H. Infection and activation of monocytes by Marburg and Ebola viruses. I Virol. 2001, 75, 11025-11033.
105. Zanella, F.; Lorens, J.B.; Link, W. High content screening: Seeing is believing. Trends Biotechnol. 2010, 28, 237-245.
106. Beiting, D.P.; Roos, D.S. A systems biological view of intracellular pathogens. Immunol. Rev. 2011, 240, 117-128.
107. MacDonald, M.L.; Lamerdin, J.; Owens, S.; Keon, B.H.; Bilter, G.K.; Shang, Z.; Huang, Z.; Yu, H.; Dias, J.; Minami, T.; Michnick, S.W.; Westwick, J.K. Identifying off-target effects and hidden phenotypes of drugs in human cells. Nat. Chem. Biol. 2006, 2, 329-337.