A Combined genetic-proteomic approach identifies residues within dengue virus NS4B critical for interaction with NS3 and viral replication

Journal of Virology

Volumn 89, Issue 14, 2015, Pages 7170-7186

  Chatel Chaix, Laurent ^a   Fischl, Wolfgang ^a   Scaturro, Pietro ^a   Cortese, Mirko ^a   Kallis, Stephanie ^a   Bartenschlager, Marie ^a   Fischer, Bernd ^b   Bartenschlager, Ralf ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

NONSTRUCTURAL PROTEIN 3; NONSTRUCTURAL PROTEIN 4B; MUTANT PROTEIN; NS3 PROTEIN, FLAVIVIRUS; NS4B PROTEIN, FLAVIVIRUS; PROTEIN BINDING; RNA HELICASE; SERINE PROTEINASE; VIRUS PROTEIN;

3' UNTRANSLATED REGION; ANIMAL CELL; ARTICLE; BINDING AFFINITY; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DENGUE VIRUS; DIMERIZATION; DNA FRAGMENTATION; ELECTROPORATION; ENDOPLASMIC RETICULUM; GENE AMPLIFICATION; GENE MAPPING; GENE REPLICATION; GENETIC ENGINEERING; GENETIC SCREENING; GLYCOSYLATION; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; IMMUNOPRECIPITATION; MASS SPECTROMETRY; NONHUMAN; PLASMID; POINT MUTATION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN CLEAVAGE; PROTEIN PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; PROTEOMICS; REVERTANT; SEQUENCE ALIGNMENT; SITE DIRECTED MUTAGENESIS; VIRUS GENOME; VIRUS REPLICATION; VIRUS STRAIN; AMINO ACID SUBSTITUTION; CELL LINE; GENE REPRESSION; GENETIC COMPLEMENTATION; GENETICS; LIVER CELL; METABOLISM; MICROBIAL VIABILITY; NUCLEOTIDE SEQUENCE; PHYSIOLOGY; REVERSE GENETICS; VIROLOGY;

ARTHROPODA; DENGUE VIRUS;

AMINO ACID SUBSTITUTION; CELL LINE; DENGUE VIRUS; DNA MUTATIONAL ANALYSIS; GENETIC COMPLEMENTATION TEST; HEPATOCYTES; HUMANS; MASS SPECTROMETRY; MICROBIAL VIABILITY; MUTANT PROTEINS; PROTEIN BINDING; PROTEIN INTERACTION MAPPING; REVERSE GENETICS; RNA HELICASES; SERINE ENDOPEPTIDASES; SUPPRESSION, GENETIC; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 84931067708     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.00867-15     Document Type: Article

References (43)

1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI. 2013. The global distribution and burden of dengue. Nature 496:504-507. http://dx.doi.org/10.1038/nature12060.
2. World Health Organization. 2009. Dengue: guidelines for diagnosis, treatment, prevention and control. World Health Organization, Geneva, Switzerland.
3. Acosta EG, Kumar A, Bartenschlager R. 2014. Revisiting dengue virushost cell interaction: new insights into molecular and cellular virology. Adv Virus Res 88:1-109. http://dx.doi.org/10.1016/B978-0-12-800098-4.00001-5.
4. Welsch S, Miller S, Romero-Brey I, Merz A, Bleck CK, Walther P, Fuller SD, Antony C, Krijnse-Locker J, Bartenschlager R. 2009. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5:365-375. http://dx.doi.org/10.1016/j.chom.2009.03.007.
5. Grief C, Galler R, Cortes LM, Barth OM. 1997. Intracellular localisation of dengue-2 RNA in mosquito cell culture using electron microscopic in situ hybridisation. Arch Virol 142:2347-2357. http://dx.doi.org/10.1007/s007050050247.
6. Mackenzie JM, Jones MK, Young PR. 1996. Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication. Virology 220:232-240. http://dx.doi.org/10.1006/viro.1996.0307.
7. Chatel-Chaix L, Bartenschlager R. 2014. Dengue virus-and hepatitis C virus-induced replication and assembly compartments: the enemy inside-caught in the web. J Virol 88:5907-5911. http://dx.doi.org/10.1128/JVI.03404-13.
8. Miller S, Kastner S, Krijnse-Locker J, Buhler S, Bartenschlager R. 2007. The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J Biol Chem 282:8873-8882. http://dx.doi.org/10.1074/jbc.M609919200.
9. Miller S, Sparacio S, Bartenschlager R. 2006. Subcellular localization and membrane topology of the Dengue virus type 2 non-structural protein 4B. J Biol Chem 281:8854-8863. http://dx.doi.org/10.1074/jbc.M512697200.
10. Lin C, Amberg SM, Chambers TJ, Rice CM. 1993. Cleavage at a novel site in the NS4A region by the yellow fever virus NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B signalase site. J Virol 67:2327-2335.
11. Roosendaal J, Westaway EG, Khromykh A, Mackenzie JM. 2006. Regulated cleavages at the West Nile virus NS4A-2K-NS4B junctions play a major role in rearranging cytoplasmic membranes and Golgi trafficking of the NS4A protein. J Virol 80:4623-4632. http://dx.doi.org/10.1128/JVI.80.9.4623-4632.2006.
12. Zou J, Xie X, Lee L.T, Chandrasekaran R, Reynaud A, Yap L, Wang QY, Dong H, Kang C, Yuan Z, Lescar J, Shi PY. 2014. Dimerization of flavivirus NS4B protein. J Virol 88:3379-3391. http://dx.doi.org/10.1128/JVI.02782-13.
13. Xie X, Wang QY, Xu HY, Qing M, Kramer L, Yuan Z, Shi PY. 2011. Inhibition of dengue virus by targeting viral NS4B protein. J Virol 85: 11183-11195. http://dx.doi.org/10.1128/JVI.05468-11.
14. Zou J, Lee LT, Wang QY, Xie X, Lu S, Yau YH, Yuan Z, Geifman SS, Kang C, Lescar J, Shi PY. 2015. Mapping the interactions between the NS4B and NS3 proteins of dengue virus. J Virol 89:3471-3483. http://dx.doi.org/10.1128/JVI.03454-14.
15. Khromykh AA, Sedlak PL, Westaway EG. 2000. cis-and trans-acting elements in flavivirus RNA replication. J Virol 74:3253-3263. http://dx.doi.org/10.1128/JVI.74.7.3253-3263.2000.
16. Umareddy I, Chao A, Sampath A, Gu F, Vasudevan SG. 2006. Dengue virus NS4B interacts with NS3 and dissociates it from single-stranded RNA. J Gen Virol 87:2605-2614. http://dx.doi.org/10.1099/vir.0.81844-0.
17. Zou J, Xie X, Wang QY, Dong H, Lee MY, Kang C, Yuan Z, Shi PY. 2015. Characterization of dengue virus NS4A and NS4B protein interaction. J Virol 89:3455-3470. http://dx.doi.org/10.1128/JVI.03453-14.
18. Li XD, Ye HQ, Deng CL, Liu SQ, Zhang HL, Shang BD, Shi PY, Yuan ZM, Zhang B. 9 January 2015. Genetic interaction between NS4A and NS4B for replication of Japanese encephalitis virus. J Gen Virol http://dx.doi.org/10.1099/vir.0.000044.
19. Wicker JA, Whiteman MC, Beasley DW, Davis CT, McGee CE, Lee JC, Higgs S, Kinney RM, Huang CY, Barrett AD. 2012. Mutational analysis of the West Nile virus NS4B protein. Virology 426:22-33. http://dx.doi.org/10.1016/j.virol.2011.11.022.
20. Youn S, Li T, McCune BT, Edeling MA, Fremont DH, Cristea IM, Diamond MS. 2012. Evidence for a genetic and physical interaction between nonstructural proteins NS1 and NS4B that modulates replication of West Nile virus. J Virol 86:7360-7371. http://dx.doi.org/10.1128/JVI.00157-12.
21. Kakumani PK, Ponia SS, S RK, Sood V, Chinnappan M, Banerjea AC, Medigeshi GR, Malhotra P, Mukherjee SK, Bhatnagar RK. 2013. Role of RNA interference (RNAi) in dengue virus replication and identification of NS4B as an RNAi suppressor. J Virol 87:8870-8883. http://dx.doi.org/10.1128/JVI.02774-12.
22. Munoz-Jordan JL, Sanchez-Burgos GG, Laurent-Rolle M, Garcia-Sastre A. 2003. Inhibition of interferon signaling by dengue virus. Proc Natl Acad Sci USA 100:14333-14338. http://dx.doi.org/10.1073/pnas.2335168100.
23. Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. 2005. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol 79:8004-8013. http://dx.doi.org/10.1128/JVI.79.13.8004-8013.2005.
24. Grant D, Tan GK, Qing M, Ng JK, Yip A, Zou G, Xie X, Yuan Z, Schreiber MJ, Schul W, Shi PY, Alonso S. 2011. A single amino acid in nonstructural protein NS4B confers virulence to dengue virus in AG129 mice through enhancement of viral RNA synthesis. J Virol 85:7775-7787. http://dx.doi.org/10.1128/JVI.00665-11.
25. Appel N, Pietschmann T, Bartenschlager R. 2005. Mutational analysis of hepatitis C virus nonstructural protein 5A: potential role of differential phosphorylation in RNA replication and identification of a genetically flexible domain. J Virol 79:3187-3194. http://dx.doi.org/10.1128/JVI.79.5.3187-3194.2005.
26. Simossis VA, Heringa J. 2005. PRALINE: a multiple sequence alignment toolbox that integrates homology-extended and secondary structure information. Nucleic Acids Res 33:W289-W294. http://dx.doi.org/10.1093/nar/gki390.
27. Cole C, Barber JD, Barton GJ. 2008. The Jpred 3 secondary structure prediction server. Nucleic Acids Res 36:W197-W201. http://dx.doi.org/10.1093/nar/gkn238.
28. Kinney RM, Butrapet S, Chang GJ, Tsuchiya KR, Roehrig JT, Bhamarapravati N, Gubler DJ. 1997. Construction of infectious cDNA clones for dengue 2 virus: strain 16681 and its attenuated vaccine derivative, strain PDK-53. Virology 230:300-308. http://dx.doi.org/10.1006/viro.1997.8500.
29. Fischl W, Bartenschlager R. 2013. High-throughput screening using dengue virus reporter genomes. Methods Mol Biol 1030:205-219. http://dx.doi.org/10.1007/978-1-62703-484-5_17.
30. Moss B, Elroy-Stein O, Mizukami T, Alexander WA, Fuerst TR. 1990. Product review. New mammalian expression vectors. Nature 348:91-92.
31. Wyatt LS, Moss B, Rozenblatt S. 1995. Replication-deficient vaccinia virus encoding bacteriophage T7 RNA polymerase for transient gene expression in mammalian cells. Virology 210:202-205. http://dx.doi.org/10.1006/viro.1995.1332.
32. Scaturro P, Trist IM, Paul D, Kumar A, Acosta EG, Byrd CM, Jordan R, Brancale A, Bartenschlager R. 2014. Characterization of the mode of action of a potent dengue virus capsid inhibitor. J Virol 88:11540-11555. http://dx.doi.org/10.1128/JVI.01745-14.
33. Kumar A, Buhler S, Selisko B, Davidson A, Mulder K, Canard B, Miller S, Bartenschlager R. 2013. 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 87:4545-4557. http://dx.doi.org/10.1128/JVI.03083-12.
34. Chatel-Chaix L, Germain MA, Motorina A, Bonneil E, Thibault P, Baril M, Lamarre D. 2013. A host YB-1 ribonucleoprotein complex is hijacked by hepatitis C virus for the control of NS3-dependent particle production. J Virol 87:11704-11720. http://dx.doi.org/10.1128/JVI.01474-13.
35. van Cleef KW, Overheul GJ, Thomassen MC, Kaptein SJ, Davidson AD, Jacobs M, Neyts J, van Kuppeveld FJ, van Rij RP. 2013. Identification of a new dengue virus inhibitor that targets the viral NS4B protein and restricts genomic RNA replication. Antiviral Res 99:165-171. http://dx.doi.org/10.1016/j.antiviral.2013.05.011.
36. Naik NG, Wu HN. 15 April 2015.Mutation of putative N-glycosylation sites on dengue NS4B decreases RNA replication. J Virol http://dx.doi.org/10.1128/JVI.00423-15.
37. Kaufusi PH, Kelley JF, Yanagihara R, Nerurkar VR. 2014. Induction of endoplasmic reticulum-derived replication-competent membrane structures by West Nile virus non-structural protein 4B. PLoS One 9:e84040. http://dx.doi.org/10.1371/journal.pone.0084040.
38. de Wispelaere M, LaCroix AJ, Yang PL. 2013. The small molecules AZD0530 and dasatinib inhibit dengue virus RNA replication via Fyn kinase. J Virol 87:7367-7381. http://dx.doi.org/10.1128/JVI.00632-13.
39. Brooks AJ, Johansson M, John AV, Xu Y, Jans DA, Vasudevan SG. 2002. The interdomain region of dengue NS5 protein that binds to the viral helicase NS3 contains independently functional importin beta 1 and importin alpha/beta-recognized nuclear localization signals. J Biol Chem 277:36399-36407. http://dx.doi.org/10.1074/jbc.M204977200.
40. Johansson M, Brooks AJ, Jans DA, Vasudevan SG. 2001. A small region of the dengue virus-encoded RNA-dependent RNA polymerase, NS5, confers interaction with both the nuclear transport receptor importinbeta and the viral helicase, NS3. J Gen Virol 82:735-745.
41. Yon C, Teramoto T, Mueller N, Phelan J, Ganesh VK, Murthy KH, Padmanabhan R. 2005. Modulation of the nucleoside triphosphatase/RNA helicase and 5'-RNA triphosphatase activities of Dengue virus type 2 nonstructural protein 3 (NS3) by interaction with NS5, the RNAdependent RNA polymerase. J Biol Chem 280:27412-27419. http://dx.doi.org/10.1074/jbc.M501393200.
42. Tay MY, Saw WG, Zhao Y, Chan KW, Singh D, Chong Y, Forwood JK, Ooi EE, Gruber G, Lescar J, Luo D, Vasudevan SG. 2015. The C-terminal 50 amino acid residues of dengue NS3 protein are important for NS3-NS5 interaction and viral replication. J Biol Chem 290:2379-2394. http://dx.doi.org/10.1074/jbc.M114.607341.
43. Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 57:289-300.