Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens

FASEB Journal

Volumn 26, Issue 4, 2012, Pages 1372-1386

  Meliopoulos, Victoria A ^a   Andersen, Lauren E ^a   Birrer, Katherine F ^a,d   Simpson, Kaylene J ^c,i   Lowenthal, John W ^b   Bean, Andrew G D ^b   Stambas, John ^d   Stewart, Cameron R ^b   Tompkins, S Mark ^a   Van Beusechem, Victor W ^e   Fraser, Iain ^f   Mhlanga, Musa ^g   Barichievy, Samantha ^g   Smith, Queta ^h   Leake, Devin ^h   Karpilow, Jon ^h   Buck, Amy ^j   Jona, Ghil ^k   Tripp, Ralph A ^a  

^a UNIVERSITY OF GEORGIA   (United States)

^b CSIRO   (Australia)

^c PETER MACCALLUM CANCER CENTRE   (Australia)

^d DEAKIN UNIVERSITY   (Australia)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^f NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^g DSI CSIR Nanotechnology Innovation Centre   (South Africa)

^h Thermo Fisher Scientific   (United States)

ⁱ UNIVERSITY OF MELBOURNE   (Australia)

^j UNIVERSITY OF EDINBURGH   (United Kingdom)

^k WEIZMANN INSTITUTE OF SCIENCE   (Israel)

more..

Author keywords

Antivirals; Genome; HTS; Meta analysis; Pathway

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MICRORNA; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE C; PROTEIN TYROSINE KINASE; RAF PROTEIN; SHORT HAIRPIN RNA; SMALL INTERFERING RNA; VIRUS PROTEIN;

BIOINFORMATICS; GENE TARGETING; GENE TECHNOLOGY; HUMAN; INFECTION SENSITIVITY; INFLUENZA; INFLUENZA VIRUS; NONHUMAN; PRIORITY JOURNAL; REVIEW; RNA INTERFERENCE; SIGNAL TRANSDUCTION; VALIDATION PROCESS; VIRUS CELL INTERACTION; VIRUS REPLICATION; VIRUS RESISTANCE;

ANIMALS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INFLUENZA A VIRUS; INFLUENZA, HUMAN; META-ANALYSIS AS TOPIC; MICRORNAS; NF-KAPPA B; PROTEIN KINASE C; RNA INTERFERENCE; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; VIRAL PROTEINS;

AVES; INFLUENZA A VIRUS; MAMMALIA; ORTHOMYXOVIRIDAE;

EID: 84860901178     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.11-193466     Document Type: Review

References (138)

1. Daszak, P., Cunningham, A. A., and Hyatt, A. D. (2000) Emerging infectious diseases of wildlife-threats to biodiversity and human health. Science 287, 443-449
2. Taubenberger, J. K., and Morens, D. M. (2010) Influenza: the once and future pandemic. Public Health Rep. 125(Suppl. 3), 16-26
3. Komar, N., and Olsen, B. (2008) Avian influenza virus (H5N1) mortality surveillance. Emerg. Infect. Dis. 14, 1176-1178 (Pubitemid 351920468)
4. World Health Organization (2009) Overview of pandemic (H1N1) 2009 in the WHO European Region. Retrieved March 11, 2010, from http://www.euro.who.int/ influenza/AH1N1/20091026-1
5. World Health Organization (2009) Seasonal influenza. Retrieved March 10, 2010, from http://www.euro.who.int/influenza/20080618-1
6. Molinari, N.-A. M., Ortega-Sanchez, I. R., Messonnier, M. L., Thompson, W. W., Wortley, P. M., Weintraub, E., and Bridges, C. B. (2007) The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine 25, 5086-5096 (Pubitemid 46879994)
7. Nagata, K., Kawaguchi, A., and Naito, T. (2008) Host factors for replication and transcription of the influenza virus genome. Rev. Med. Virol. 18, 247-260 (Pubitemid 352018848)
8. Zhou, Z., Xue, Q., Wan, Y., Yang, Y., Wang, J., and Hung, T. (2011) Lysosome-associated membrane glycoprotein 3 is in- volved in influenza A virus replication in human lung epithelial (A549) cells. Virol. J. 8, 384
9. Su, B., Wurtzer, S., Rameix-Welti, M. A., Dwyer, D., van der Werf, S., Naffakh, N., Clavel, F., and Labrosse, B. (2009) Enhancement of the influenza A hemagglutinin (HA)-mediated cell-cell fusion and virus entry by the viral neuraminidase (NA). PloS One 4, e8495
10. Kumar, N., Xin, Z. T., Liang, Y., and Ly, H. (2008) NF-κB signaling differentially regulates influenza virus RNA synthesis. J. Virol. 82, 9880-9889
11. Bruce, E. A., Digard, P., and Stuart, A. D. (2010) The Rab11 pathway is required for influenza A virus budding and filament formation. J. Virol. 84, 5848-5859
12. Rossman, J. S., and Lamb, R. A. (2011) Influenza virus assembly and budding. Virology 411, 229-236
13. Leung, R. K., and Whittaker, P. A. (2005) RNA interference: from gene silencing to gene-specific therapeutics. Pharmacol. Ther. 107, 222-239 (Pubitemid 40910042)
14. Tripp, R. A., and Tompkins, S. M. (2009) Therapeutic applications of RNAi for silencing virus replication. Methods Mol. Biol. 555, 43-61
15. Bagasra, O., and Prilliman, K. R. (2004) RNA interference: the molecular immune system. J. Mol. Histol. 35, 545-553 (Pubitemid 41404640)
16. Blair, C. D. (2011) Mosquito RNAi is the major innate immune pathway controlling arbovirus infection and transmission. Future Microbiol. 6, 265-277
17. Hale, B. G., Randall, R. E., Ortin, J., and Jackson, D. (2008) The multifunctional NS1 protein of influenza A viruses. J. Gen. Virol. 89, 2359-2376
18. Kim, D. H., and Rossi, J. J. (2007) Strategies for silencing human disease using RNA interference. Nat. Rev. Genet. 8, 173-184
19. Kim, V. N., Han, J., and Siomi, M. C. (2009) Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell. Biol. 10, 126-139
20. Held, K., Junker, A., Dornmair, K., Meinl, E., Sinicina, I., Brandt, T., Theil, D., and Derfuss, T. (2011) Expression of herpes simplex virus 1-encoded microRNAs in human trigeminal ganglia and their relation to local T-cell infiltrates. J. Virol. 85, 9680-9685
21. Tirabassi, R., Hook, L., Landais, I., Grey, F., Meyers, H., Hewitt, H., and Nelson, J. (2011) Human cytomegalovirus US7 is regulated synergistically by two virally-encoded miRNAs and by two distinct mechanisms. J. Virol. 85, 11938-11944
22. Pfeffer, S., Zavolan, M., Grasser, F. A., Chien, M., Russo, J. J., Ju, J., John, B., Enright, A. J., Marks, D., Sander, C., and Tuschl, T. (2004) Identification of virus-encoded microRNAs. Science 304, 734-736 (Pubitemid 38560879)
23. Hughes, R. A., Miklos, A. E., and Ellington, A. D. (2011) Gene synthesis methods and applications. Methods Enzymol. 498, 277-309
24. Zhang, W., and Tripp, R. A. (2008) RNA interference inhibits respiratory syncytial virus replication and disease pathogenesis without inhibiting priming of the memory immune response. J. Virol. 82, 12221-12231
25. Sakurai, K., Chomchan, P., and Rossi, J. J. (2010) Silencing of gene expression in cultured cells using small interfering RNAs. Curr. Protoc. Cell Biol. 47, 27.1.1-27.1.28
26. Snead, N. M., and Rossi, J. J. (2010) Biogenesis and function of endogenous and exogenous siRNAs. Wiley Interdiscip. Rev. RNA 1, 117-131
27. Blakely, K., Ketela, T., and Moffat, J. (2011) Pooled lentiviral shRNA screening for functional genomics in mammalian cells. Methods Mol. Biol. 781, 161-182
28. Gobeil, S., Zhu, X., Doillon, C. J., and Green, M. R. (2008) A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene. Genes Dev. 22, 2932-2940
29. Yeh, M. H., Tsai, T. C., Kuo, H. P., Chang, N. W., Lee, M. R., Chung, J. G., Tsai, M. H., Liu, J. Y., and Kao, M. C. (2011) Lentiviral short hairpin RNA screen of human kinases and phosphatases to identify potential biomarkers in oral squamous cancer cells. Intl. J. Oncol. 39, 1221-1231
30. 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., Adams, D. J., Xavier, R. J., Farzan, M., and Elledge, S. J. (2009) The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139, 1243-1254
31. Hao, L., Sakurai, A., Watanabe, T., Sorensen, E., Nidom, C. A., Newton, M. A., Ahlquist, P., and Kawaoka, Y. (2008) Drosophila RNAi screen identifies host genes important for influenza virus replication. Nature 454, 890-893
32. Karlas, A., Machuy, N., Shin, Y., Pleissner, K. P., Artarini, A., Heuer, D., Becker, D., Khalil, H., Ogilvie, L. A., Hess, S., Maurer, A. P., Muller, E., Wolff, T., Rudel, T., and Meyer, T. F. (2010) Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 463, 818-822
33. Konig, R., Stertz, S., Zhou, Y., Inoue, A., Hoffmann, H. H., Bhattacharyya, S., Alamares, J. G., Tscherne, D. M., Ortigoza, M. B., Liang, Y., Gao, Q., Andrews, S. E., Bandyopadhyay, S., De Jesus, P., Tu, B. P., Pache, L., Shih, C., Orth, A., Bonamy, G., Miraglia, L., Ideker, T., Garcia-Sastre, A., Young, J. A., Palese, P., Shaw, M. L., and Chanda, S. K. (2009) Human host factors required for influenza virus replication. Nature 463, 813-817
34. Kisielow, M., Kleiner, S., Nagasawa, M., Faisal, A., and Nagamine, Y. (2002) Isoform-specific knockdown and expression of adaptor protein ShcA using small interfering RNA. Biochem. J. 363, 1-5 (Pubitemid 34280605)
35. Holen, T., Amarzguioui, M., Wiiger, M. T., Babaie, E., and Prydz, H. (2002) Positional effects of short interfering RNAs targeting the human coagulation trigger tissue factor. Nucleic Acids Res. 30, 1757-1766 (Pubitemid 34679753)
36. Birmingham, A., Selfors, L. M., Forster, T., Wrobel, D., Kennedy, C. J., Shanks, E., Santoyo-Lopez, J., Dunican, D. J., Long, A., Kelleher, D., Smith, Q., Beijersbergen, R. L., Ghazal, P., and Shamu, C. E. (2009) Statistical methods for analysis of high-throughput RNA interference screens. Nat. Methods 6, 569 -575
37. Wu, S., Metcalf, J. P., and Wu, W. (2011) Innate immune response to influenza virus. Curr. Opin. Infect. Dis. 24, 235-240
38. Barchet, W., Krug, A., Cella, M., Newby, C., Fischer, J. A., Dzionek, A., Pekosz, A., and Colonna, M. (2005) Dendritic cells respond to influenza virus through TLR7- and PKRindependent pathways. Eur. J. Immunol. 35, 236-242 (Pubitemid 40123870)
39. Lund, J. M., Alexopoulou, L., Sato, A., Karow, M., Adams, N. C., Gale, N. W., Iwasaki, A., and Flavell, R. A. (2004) Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc. Natl. Acad. Sci. U. S. A. 101, 5598-5603 (Pubitemid 38481202)
40. Hayden, F. G., Fritz, R., Lobo, M. C., Alvord, W., Strober, W., and Straus, S. E. (1998) Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J. Clin. Invest. 101, 643-649 (Pubitemid 28084248)
41. Kim, D. H., Longo, M., Han, Y., Lundberg, P., Cantin, E., and Rossi, J. J. (2004) Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat. Biotechnol. 22, 321-325 (Pubitemid 38295765)
42. Hornung, V., Guenthner-Biller, M., Bourquin, C., Ablasser, A., Schlee, M., Uematsu, S., Noronha, A., Manoharan, M., Akira, S., de Fougerolles, A., Endres, S., and Hartmann, G. (2005) Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11, 263-270 (Pubitemid 40460553)
43. Sioud, M. (2005) Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J. Mol. Biol. 348, 1079-1090
44. Reynolds, A., Anderson, E. M., Vermeulen, A., Fedorov, Y., Robinson, K., Leake, D., Karpilow, J., Marshall, W. S., and Khvorova, A. (2006) Induction of the interferon response by siRNA is cell type- and duplex length-dependent. RNA 12, 988-993 (Pubitemid 43788117)
45. Robbins, M., Judge, A., Liang, L., McClintock, K., Yaworski, E., and MacLachlan, I. (2007) 2′-O-methyl-modified RNAs act as TLR7 antagonists. Mol. Ther. 15, 1663-1669 (Pubitemid 47289010)
46. Sioud, M., Furset, G., and Cekaite, L. (2007) Suppression of immunostimulatory siRNA-driven innate immune activation by 2′-modified RNAs. Biochem. Biophys. Res. Commun. 361, 122-126 (Pubitemid 47102276)
47. Eberle, F., Giessler, K., Deck, C., Heeg, K., Peter, M., Richert, C., and Dalpke, A. H. (2008) Modifications in small interfering RNA that separate immunostimulation from RNA interference. J. Immunol. 180, 3229-3237
48. Hirsch, A. J. (2010) The use of RNAi-based screens to identify host proteins involved in viral replication. Future Microbiol. 5, 303-311
49. Sigoillot, F. D., and King, R. W. (2011) Vigilance and validation: Keys to success in RNAi screening. ACS Chem. Biol. 6, 47-60
50. Jackson, A. L., Burchard, J., Leake, D., Reynolds, A., Schelter, J., Guo, J., Johnson, J. M., Lim, L., Karpilow, J., Nichols, K., Marshall, W., Khvorova, A., and Linsley, P. S. (2006) Positionspecific chemical modification of siRNAs reduces "off-target"transcript silencing. RNA 12, 1197-1205 (Pubitemid 43990545)
51. Wu, J. Q., Dwyer, D. E., Dyer, W. B., Yang, Y. H., Wang, B., and Saksena, N. K. (2011) Genome-wide analysis of primary CD4+and CD8+ T-cell transcriptomes shows evidence for a network of enriched pathways associated with HIV disease. Retrovirology 8, 18
52. Lee, R. C., Feinbaum, R. L., and Ambros, V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854 (Pubitemid 24014542)
53. Lee, R. C., and Ambros, V. (2001) An extensive class of small RNAs in Caenorhabditis elegans. Science 294, 862-864 (Pubitemid 33032105)
54. Lau, N. C., Lim, L. P., Weinstein, E. G., and Bartel, D. P. (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294, 858-862 (Pubitemid 33032104)
55. Lagos-Quintana, M., Rauhut, R., Lendeckel, W., and Tuschl, T. (2001) Identification of novel genes coding for small expressed RNAs. Science 294, 853-858 (Pubitemid 33032103)
56. Griffiths-Jones, S., Grocock, R. J., van Dongen, S., Bateman, A., and Enright, A. J. (2006) miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34, D140-D144
57. Griffiths-Jones, S. (2004) The microRNA registry. Nucleic Acids Res. 32, D109-D111
58. Jopling, C. L., Yi, M., Lancaster, A. M., Lemon, S. M., and Sarnow, P. (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 309, 1577-1581 (Pubitemid 41266486)
59. Santhakumar, D., Forster, T., Laqtom, N. N., Fragkoudis, R., Dickinson, P., Abreu-Goodger, C., Manakov, S. A., Choudhury, N. R., Griffiths, S. J., Vermeulen, A., Enright, A. J., Dutia, B., Kohl, A., Ghazal, P., and Buck, A. H. (2010) Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs. Proc. Natl. Acad. Sci. U. S. A. 107, 13830-13835
60. Vermeulen, A., Robertson, B., Dalby, A. B., Marshall, W. S., Karpilow, J., Leake, D., Khvorova, A., and Baskerville, S. (2007) Double-stranded regions are essential design components of potent inhibitors of RISC function. RNA 13, 723-730 (Pubitemid 46641531)
61. Ehrhardt, C., Wolff, T., Pleschka, S., Planz, O., Beermann, W., Bode, J. G., Schmolke, M., and Ludwig, S. (2007) Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses. J. Virol. 81, 3058-3067 (Pubitemid 46456615)
62. Pleschka, S. (2008) RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade. Biol. Chem. 389, 1273-1282
63. Porotto, M., Orefice, G., Yokoyama, C. C., Mungall, B. A., Realubit, R., Sganga, M. L., Aljofan, M., Whitt, M., Glickman, F., and Moscona, A. (2009) Simulating henipavirus multicycle replication in a screening assay leads to identification of a promising candidate for therapy. J. Virol. 83, 5148-5155
64. Bredenbeek, P. J., Molenkamp, R., Spaan, W. J., Deubel, V., Marianneau, P., Salvato, M. S., Moshkoff, D., Zapata, J., Tikhonov, I., Patterson, J., Carrion, R., Ticer, A., Brasky, K., and Lukashevich, I. S. (2006) A recombinant Yellow Fever 17D vaccine expressing Lassa virus glycoproteins. Virology 345, 299-304 (Pubitemid 43189891)
65. Geisbert, T. W., Bailey, M., Hensley, L., Asiedu, C., Geisbert, J., Stanley, D., Honko, A., Johnson, J., Mulangu, S., Pau, M. G., Custers, J., Vellinga, J., Hendriks, J., Jahrling, P., Roederer, M., Goudsmit, J., Koup, R., and Sullivan, N. J. (2011) Recombinant adenovirus serotype 26 (Ad26) and Ad35 vaccine vectors bypass immunity to Ad5 and protect nonhuman primates against ebolavirus challenge. J. Virol. 85, 4222- 4233
66. Zhang, W., Xue, T., Wu, X., Zhang, P., Zhao, G., Peng, D., Hu, S., Wang, X., Liu, X., and Liu, W. (2011) Increase in viral yield in eggs and MDCK cells of reassortant H5N1 vaccine candidate viruses caused by insertion of 38 amino acids into the NA stalk. Vaccine 29, 8032-8041
67. Shapira, S. D., Gat-Viks, I., Shum, B. O., Dricot, A., de Grace, M. M., Wu, L., Gupta, P. B., Hao, T., Silver, S. J., Root, D. E., Hill, D. E., Regev, A., and Hacohen, N. (2009) A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell 139, 1255-1267
68. Ganter, B., and Giroux, C. N. (2008) Emerging applications of network and pathway analysis in drug discovery and development. Curr. Opin. Drug Disc. Dev. 11, 86-94
69. Friedman, A. A., Tucker, G., Singh, R., Yan, D., Vinayagam, A., Hu, Y., Binari, R., Hong, P., Sun, X., Porto, M., Pacifico, S., Murali, T., Finley, R. L., Jr., Asara, J. M., Berger, B., and Perrimon, N. (2011) Proteomic and functional genomic landscape of receptor tyrosine kinase and ras to extracellular signal-regulated kinase signaling. Sci. Signal. 4, rs10
70. Yore, M. M., Kettenbach, A. N., Sporn, M. B., Gerber, S. A., and Liby, K. T. (2011) Proteomic analysis shows synthetic oleanane triterpenoid binds to mTOR. PloS One 6, e22862
71. Ruan, L., Li, X. H., Wan, X. X., Yi, H., Li, C., Li, M. Y., Zhang, P. F., Zeng, G. Q., Qu, J. Q., He, Q. Y., Li, J. H., Chen, Y., Chen, Z. C., and Xiao, Z. Q. (2011) Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics. Proteome Sci. 9, 35
72. Satoh, J., and Tabunoki, H. (2011) Comprehensive analysis of human microRNA target networks. BioData Mining 4, 17
73. Glaab, E., Baudot, A., Krasnogor, N., and Valencia, A. (2010) Extending pathways and processes using molecular interaction networks to analyse cancer genome data. BMC Bioinformatics 11, 597
74. Jianu, R., Yu, K., Cao, L., Nguyen, V., Salomon, A. R., and Laidlaw, D. H. (2010) Visual integration of quantitative proteomic data, pathways, and protein interactions. IEEE Trans. Vis. Comput. Graphics 16, 609-620
75. Bankhead, A., 3rd, Sach, I., Ni, C., LeMeur, N., Kruger, M., Ferrer, M., Gentleman, R., and Rohl, C. (2009) Knowledgebased identification of essential signaling from genome-scale siRNA experiments. BMC Systems Biol. 3, 80
76. Fraser, I. D., and Germain, R. N. (2009) Navigating the network: signaling cross-talk in hematopoietic cells. Nat. Immunol. 10, 327-331
77. Prenzel, N., Fischer, O. M., Streit, S., Hart, S., and Ullrich, A. (2001) The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr. Relat. Cancer 8, 11-31 (Pubitemid 32520251)
78. Weiss, F. U., Wallasch, C., Campiglio, M., Issing, W., and Ullrich, A. (1997) Distinct characteristics of heregulin signals mediated by HER3 or HER4. J. Cell. Physiol. 173, 187-195 (Pubitemid 27481128)
79. Jones, F. E., Welte, T., Fu, X. Y., and Stern, D. F. (1999) ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation. J. Cell Biol. 147, 77-88
80. Kainulainen, V., Sundvall, M., Maatta, J. A., Santiestevan, E., Klagsbrun, M., and Elenius, K. (2000) A natural ErbB4 isoform that does not activate phosphoinositide 3-kinase mediates proliferation but not survival or chemotaxis. J. Biol. Chem. 275, 8641-8649 (Pubitemid 30180214)
81. Long, W., Wagner, K. U., Lloyd, K. C., Binart, N., Shillingford, J. M., Hennighausen, L., and Jones, F. E. (2003) Impaired differentiation and lactational failure of Erbb4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5. Development 130, 5257-5268 (Pubitemid 37369683)
82. Khor, R., McElroy, L. J., and Whittaker, G. R. (2003) The ubiquitin-vacuolar protein sorting system is selectively required during entry of influenza virus into host cells. Traffic 4, 857-868 (Pubitemid 37547895)
83. Lakadamyali, M., Rust, M. J., and Zhuang, X. (2006) Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes. Cell 124, 997-1009 (Pubitemid 43344239)
84. Eierhoff, T., Hrincius, E. R., Rescher, U., Ludwig, S., and Ehrhardt, C. (2010) The epidermal growth factor receptor (EGFR) promotes uptake of influenza A viruses (IAV) into host cells. PLoS Pathog. 6, e1001099
85. Toker, A. (1998) Signaling through protein kinase C. Front. Biosci. 3, D1134-D1147
86. Hoffmann, H. H., Palese, P., and Shaw, M. L. (2008) Modulation of influenza virus replication by alteration of sodium ion transport and protein kinase C activity. Antiviral Res. 80, 124-134
87. + channels in respiratory epithelia. Proc. Natl. Acad. Sci. U. S. A. 97, 10282-10287
88. Lazrak, A., Iles, K. E., Liu, G., Noah, D. L., Noah, J. W., and Matalon, S. (2009) Influenza virus M2 protein inhibits epithelial sodium channels by increasing reactive oxygen species. FASEB J. 23, 3829-3842
89. Sieczkarski, S. B., and Whittaker, G. R. (2005) Characterization of the host cell entry of filamentous influenza virus. Arch. Virol. 150, 1783-1796 (Pubitemid 41176635)
90. Constantinescu, S. N., Cernescu, C. D., and Popescu, L. M. (1991) Effects of protein kinase C inhibitors on viral entry and infectivity. FEBS Lett. 292, 31-33
91. Root, C. N., Wills, E. G., McNair, L. L., and Whittaker, G. R. (2000) Entry of influenza viruses into cells is inhibited by a highly specific protein kinase C inhibitor. J. Gen. Virol. 81, 2697-2705
92. Neri, L. M., Borgatti, P., Capitani, S., and Martelli, A. M. (2002) The nuclear phosphoinositide 3-kinase/AKT pathway: a new second messenger system. Biochim. Biophys. Acta 1584, 73-80 (Pubitemid 35217879)
93. Vanhaesebroeck, B., Ali, K., Bilancio, A., Geering, B., and Foukas, L. C. (2005) Signalling by PI3K isoforms: insights from gene-targeted mice. Trends Biochem. Sci. 30, 194-204 (Pubitemid 40463309)
94. Ehrhardt, C., Marjuki, H., Wolff, T., Nurnberg, B., Planz, O., Pleschka, S., and Ludwig, S. (2006) Bivalent role of the phosphatidylinositol-3-kinase (PI3K) during influenza virus infection and host cell defence. Cell. Microbiol. 8, 1336-1348
95. Kujime, K., Hashimoto, S., Gon, Y., Shimizu, K., and Horie, T. (2000) p38 mitogen-activated protein kinase and c-jun-NH2- terminal kinase regulate RANTES production by influenza virus-infected human bronchial epithelial cells. J. Immunol. 164, 3222-3228 (Pubitemid 30148985)
96. Ludwig, S., Pleschka, S., Planz, O., and Wolff, T. (2006) Ringing the alarm bells: signalling and apoptosis in influenza virus infected cells. Cell. Microbiol. 8, 375-386 (Pubitemid 43356029)
97. Ludwig, S., Planz, O., Pleschka, S., and Wolff, T. (2003) Influenza-virus-induced signaling cascades: targets for antiviral therapy? Trends Mol. Med. 9, 46-52 (Pubitemid 36313864)
98. Pleschka, S., Wolff, T., Ehrhardt, C., Hobom, G., Planz, O., Rapp, U. R., and Ludwig, S. (2001) Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade. Nat. Cell Biol. 3, 301-305 (Pubitemid 32201326)
99. Pearson, G., Robinson, F., Beers Gibson, T., Xu, B. E., Karandikar, M., Berman, K., and Cobb, M. H. (2001) Mitogenactivated protein (MAP) kinase pathways: regulation and physiological functions. Endocr. Rev. 22, 153-183 (Pubitemid 32458157)
100. Dong, C., Davis, R. J., and Flavell, R. A. (2002) MAP kinases in the immune response. Annu. Rev. Immunol. 20, 55-72 (Pubitemid 34293420)
101. Ludwig, S., Wolff, T., Ehrhardt, C., Wurzer, W. J., Reinhardt, J., Planz, O., and Pleschka, S. (2004) MEK inhibition impairs influenza B virus propagation without emergence of resistant variants. FEBS Lett. 561, 37-43 (Pubitemid 38317295)
102. Marjuki, H., Alam, M. I., Ehrhardt, C., Wagner, R., Planz, O., Klenk, H. D., Ludwig, S., and Pleschka, S. (2006) Membrane accumulation of influenza A virus hemagglutinin triggers nuclear export of the viral genome via protein kinase Calphamediated activation of ERK signaling. J. Biol. Chem. 281, 16707-16715
103. Marjuki, H., Yen, H. L., Franks, J., Webster, R. G., Pleschka, S., and Hoffmann, E. (2007) Higher polymerase activity of a human influenza virus enhances activation of the hemagglutinin-induced Raf/MEK/ERK signal cascade. Virol. J. 4, 134
104. Guillot, L., Le Goffic, R., Bloch, S., Escriou, N., Akira, S., Chignard, M., and Si-Tahar, M. (2005) Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J. Biol. Chem. 280, 5571-5580 (Pubitemid 40280035)
105. Karin, M., Liu, Z., and Zandi, E. (1997) AP-1 function and regulation. Curr. Opin. Cell Biol. 9, 240-246 (Pubitemid 27135992)
106. Ludwig, S., Wang, X., Ehrhardt, C., Zheng, H., Donelan, N., Planz, O., Pleschka, S., Garcia-Sastre, A., Heins, G., and Wolff, T. (2002) The influenza A virus NS1 protein inhibits activation of Jun N-terminal kinase and AP-1 transcription factors. J. Virol. 76, 11166-11171 (Pubitemid 35176236)
107. Pahl, H. L. (1999) Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18, 6853-6866
108. Chu, W. M., Ostertag, D., Li, Z. W., Chang, L., Chen, Y., Hu, Y., Williams, B., Perrault, J., and Karin, M. (1999) JNK2 and IKKßare required for activating the innate response to viral infection. Immunity 11, 721-731 (Pubitemid 30030711)
109. Wurzer, W. J., Ehrhardt, C., Pleschka, S., Berberich-Siebelt, F., Wolff, T., Walczak, H., Planz, O., and Ludwig, S. (2004) NF-κB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation. J. Biol. Chem. 279, 30931-30937 (Pubitemid 39037751)
110. Nimmerjahn, F., Dudziak, D., Dirmeier, U., Hobom, G., Riedel, A., Schlee, M., Staudt, L. M., Rosenwald, A., Behrends, U., Bornkamm, G. W., and Mautner, J. (2004) Active NF-κB signalling is a prerequisite for influenza virus infection. J. Gen. Virol. 85, 2347-2356 (Pubitemid 39162607)
111. Wurzer, W. J., Planz, O., Ehrhardt, C., Giner, M., Silberzahn, T., Pleschka, S., and Ludwig, S. (2003) Caspase 3 activation is essential for efficient influenza virus propagation. EMBO J. 22, 2717-2728 (Pubitemid 36712368)
112. Kramer, A., Liashkovich, I., Oberleithner, H., Ludwig, S., Mazur, I., and Shahin, V. (2008) Apoptosis leads to a degradation of vital components of active nuclear transport and a dissociation of the nuclear lamina. Proc. Natl. Acad. Sci. U. S. A. 105, 11236-11241
113. Faleiro, L., and Lazebnik, Y. (2000) Caspases disrupt the nuclear-cytoplasmic barrier. J. Cell Biol. 151, 951-959
114. Brazma, A., Hingamp, P., Quackenbush, J., Sherlock, G., Spellman, P., Stoeckert, C., Aach, J., Ansorge, W., Ball, C. A., Causton, H. C., Gaasterland, T., Glenisson, P., Holstege, F. C., Kim, I. F., Markowitz, V., Matese, J. C., Parkinson, H., Robinson, A., Sarkans, U., Schulze-Kremer, S., Stewart, J., Taylor, R., Vilo, J., and Vingron, M. (2001) Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat. Genet. 29, 365-371 (Pubitemid 34326681)
115. Brazma, A. (2009) Minimum information about a microarray experiment (MIAME)-successes, failures, challenges. Sci. World J. 9, 420-423
116. Haney, S. A. (2007) Increasing the robustness and validity of RNAi screens. Pharmacogenomics 8, 1037-1049
117. Schulte, J., Sepp, K. J., Wu, C., Hong, P., and Littleton, J. T. (2011) High-content chemical and RNAi screens for suppressors of neurotoxicity in a Huntington's disease model. PloS One 6, e23841
118. Pache, L., Konig, R., and Chanda, S. K. (2011) Identifying HIV-1 host cell factors by genome-scale RNAi screening. Methods 53, 3-12
119. Genovesio, A., Giardini, M. A., Kwon, Y. J., de Macedo Dossin, F., Choi, S. Y., Kim, N. Y., Kim, H. C., Jung, S. Y., Schenkman, S., Almeida, I. C., Emans, N., and Freitas-Junior, L. H. (2011) Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection. PLoS One 6, e19733
120. Genovesio, A., Kwon, Y. J., Windisch, M. P., Kim, N. Y., Choi, S. Y., Kim, H. C., Jung, S., Mammano, F., Perrin, V., Boese, A. S., Casartelli, N., Schwartz, O., Nehrbass, U., and Emans, N. (2011) Automated genome-wide visual profiling of cellular proteins involved in HIV infection. J. Biomol. Screen. 16, 945-958
121. Severson, W. E., McDowell, M., Ananthan, S., Chung, D. H., Rasmussen, L., Sosa, M. I., White, E. L., Noah, J., and Jonsson, C. B. (2008) High-throughput screening of a 100,000-compound library for inhibitors of influenza A virus (H3N2). J. Biomol. Screen. 13, 879-887
122. Shih, S. R., Chu, T. Y., Reddy, G. R., Tseng, S. N., Chen, H. L., Tang, W. F., Wu, M. S., Yeh, J. Y., Chao, Y. S., Hsu, J. T., Hsieh, H. P., and Horng, J. T. (2010) Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity. J. Biomed. Sci. 17, 13
123. Borjabad, A., Morgello, S., Chao, W., Kim, S. Y., Brooks, A. I., Murray, J., Potash, M. J., and Volsky, D. J. (2011) Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders. PLoS Pathog. 7, e1002213
124. Geiss, G. K., An, M. C., Bumgarner, R. E., Hammersmark, E., Cunningham, D., and Katze, M. G. (2001) Global impact of influenza virus on cellular pathways is mediated by both replicationdependent and -independent events. J. Virol. 75, 4321-4331 (Pubitemid 32410144)
125. Geiss, G. K., Bumgarner, R. E., An, M. C., Agy, M. B., van 't Wout, A. B., Hammersmark, E., Carter, V. S., Upchurch, D., Mullins, J. I., and Katze, M. G. (2000) Large-scale monitoring of host cell gene expression during HIV-1 infection using cDNA microarrays. Virology 266, 8-16 (Pubitemid 30048631)
126. Chang, Y. E., and Laimins, L. A. (2000) Microarray analysis identifies interferon-inducible genes and Stat-1 as major transcriptional targets of human papillomavirus type 31. J. Virol. 74, 4174-4182 (Pubitemid 30214423)
127. Khodarev, N. N., Advani, S. J., Gupta, N., Roizman, B., and Weichselbaum, R. R. (1999) Accumulation of specific RNAs encoding transcriptional factors and stress response proteins against a background of severe depletion of cellular RNAs in cells infected with herpes simplex virus 1. Proc. Natl. Acad. Sci. U. S. A. 96, 12062-12067 (Pubitemid 29502858)
128. Der, S. D., Zhou, A., Williams, B. R., and Silverman, R. H. (1998) Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc. Natl. Acad. Sci. U. S. A. 95, 15623-15628 (Pubitemid 29018750)
129. Legendre, M., Audic, S., Poirot, O., Hingamp, P., Seltzer, V., Byrne, D., Lartigue, A., Lescot, M., Bernadac, A., Poulain, J., Abergel, C., and Claverie, J. M. (2010) mRNA deep sequencing reveals 75 new genes and a complex transcriptional landscape in Mimivirus. Genome Res. 20, 664-674
130. Yang, Z., Bruno, D. P., Martens, C. A., Porcella, S. F., and Moss, B. (2010) Simultaneous high-resolution analysis of vaccinia virus and host cell transcriptomes by deep RNA sequencing. Proc. Natl. Acad. Sci. U. S. A. 107, 11513-11518
131. Lefebvre, G., Desfarges, S., Uyttebroeck, F., Munoz, M., Beerenwinkel, N., Rougemont, J., Telenti, A., and Ciuffi, A. (2010) Analysis of HIV-1 expression level and sense of transcription by high-throughput sequencing of the infected cell. J. Virol. 85, 6205-6211
132. Fields, S., and Song, O. (1989) A novel genetic system to detect protein-protein interactions. Nature 340, 245-246 (Pubitemid 19171591)
133. Calderwood, M. A., Venkatesan, K., Xing, L., Chase, M. R., Vazquez, A., Holthaus, A. M., Ewence, A. E., Li, N., Hirozane- Kishikawa, T., Hill, D. E., Vidal, M., Kieff, E., and Johannsen, E. (2007) Epstein-Barr virus and virus human protein interaction maps. Proc. Natl. Acad. Sci. U. S. A. 104, 7606-7611 (Pubitemid 47185953)
134. von Brunn, A., Teepe, C., Simpson, J. C., Pepperkok, R., Friedel, C. C., Zimmer, R., Roberts, R., Baric, R., and Haas, J. (2007) Analysis of intraviral protein-protein interactions of the SARS coronavirus ORFeome. PloS One 2, e459
135. de Chassey, B., Navratil, V., Tafforeau, L., Hiet, M. S., Aublin-Gex, A., Agaugue, S., Meiffren, G., Pradezynski, F., Faria, B. F., Chantier, T., Le Breton, M., Pellet, J., Davoust, N., Mangeot, P. E., Chaboud, A., Penin, F., Jacob, Y., Vidalain, P. O., Vidal, M., Andre, P., Rabourdin-Combe, C., and Lotteau, V. (2008) Hepatitis C virus infection protein network. Mol. Syst. Biol. 4, 230
136. Karlas, A., Machuy, N., Shin, Y., Pleissner, K. P., Artarini, A., Heuer, D., Becker, D., Khalil, H., Ogilvie, L. A., Hess, S., Maurer, A. P., Muller, E., Wolff, T., Rudel, T., and Meyer, T. F. (2010) Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 463, 818-822
137. Konig, R., Stertz, S., Zhou, Y., Inoue, A., Hoffmann, H. H., Bhattacharyya, S., Alamares, J. G., Tscherne, D. M., Ortigoza, M. B., Liang, Y., Gao, Q., Andrews, S. E., Bandyopadhyay, S., De Jesus, P., Tu, B. P., Pache, L., Shih, C., Orth, A., Bonamy, G., Miraglia, L., Ideker, T., Garcia-Sastre, A., Young, J. A., Palese, P., Shaw, M. L., and Chanda, S. K. (2010) Human host factors required for influenza virus replication. Nature 463, 813-817
138. Brass, A. L., Dykxhoorn, D. M., Benita, Y., Yan, N., Engelman, A., Xavier, R. J., Lieberman, J., and Elledge, S. J. (2008) Identification of host proteins required for HIV infection through a functional genomic screen. Science 319, 921-926 (Pubitemid 351263756)