Dengue virus-1 NS5 genetic variant associated with a severe clinical infection: Possible reduction of the innate immune response by inhibition of interferon type 1 and the Janus kinase-signal transducer and activator of transcription signaling pathway

Delgado‑Enciso,Iván; López‑Lemus,Uriel  A.; Valcarcel‑Gamiño,Jose  A.; Rodriguez‑Sanchez,Iram  P.; Valle‑Reyes,Salvador; Martinez‑Fierro,Margarita  L.; Melnikov,Valery; Guzmán‑Esquivel,José; Vaca‑Paniagua,Felipe; Valdez‑Velazquez,Laura  L.; Baltazar‑Rodriguez,Luz   M.; Soriano‑Hernandez,Alejandro D.; Paz‑Michel,Brenda; Espinoza‑Gómez,Francisco

doi:10.3892/ijmm.2018.3395

Dengue virus-1 NS5 genetic variant associated with a severe clinical infection: Possible reduction of the innate immune response by inhibition of interferon type 1 and the Janus kinase-signal transducer and activator of transcription signaling pathway

Authors:
- Iván Delgado‑Enciso
- Uriel A. López‑Lemus
- Jose A. Valcarcel‑Gamiño
- Iram P. Rodriguez‑Sanchez
- Salvador Valle‑Reyes
- Margarita L. Martinez‑Fierro
- Valery Melnikov
- José Guzmán‑Esquivel
- Felipe Vaca‑Paniagua
- Laura L. Valdez‑Velazquez
- Luz M. Baltazar‑Rodriguez
- Alejandro D. Soriano‑Hernandez
- Brenda Paz‑Michel
- Francisco Espinoza‑Gómez
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Affiliations: Department of Public Health, School of Medicine, University of Colima, Colima, Colima 28030, Mexico, Department of Chemical Sciences, School of Chemical Sciences, University of Colima, Coquimatlán, Colima 28400, Mexico, Genetics Department, School of Medicine, Nuevo León Autonomous University, Monterrey, Nuevo León 64460, Mexico, Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Zacatecas Autonomous University, Zacatecas, Zacatecas 98160, Mexico, Department of Research, Mexican Social Security Institute, Villa de Alvarez, Colima 28983, Mexico, Biomedicine Unit, School of Graduate Studies‑Iztacala, National Autonomous University of Mexico, Mexico City, State of Mexico 04510, Mexico, Esteripharma Mexico, Mexico City, State of Mexico 03100, Mexico
Published online on: January 17, 2018 https://doi.org/10.3892/ijmm.2018.3395
Pages: 2263-2269

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Abstract

Dengue virus (DENV) is currently considered as one of the most important mosquito-borne viral pathogens affecting humans. Genetic variations in viruses are likely to be a condition for more effective evasion of the immune system and resulting in severe clinical consequences. The DENV‑1 NS5 gene was sequenced to establish whether during an epidemic burst there were genetic variations of the virus and whether any variant was associated (through a case‑control design) with severe clinical behavior. A total of 31 patients positive for DENV‑1 were enrolled. Among the nucleotide differences between the sequences, only two generated amino acid changes. The variants 124Met/166Ser (amino acid positions according to the report GenBank AJL35015.1), were associated with a severe clinical course of the disease. Via in silico tests, it was identified that the variations generate changes in the protein probably affecting the function of type‑1 interferon, either at the level of its receptor or by interfering with the Janus kinase‑signal transducer and activator of transcription signaling pathway.

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1	Gubler DJ: Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 11:480–496. 1998.PubMed/NCBI
2	Kuno G, Chang GJ, Tsuchiya KR, Karabatsos N and Cropp CB: Phylogeny of the genus Flavivirus. J Virol. 72:73–83. 1998.PubMed/NCBI
3	Leitmeyer KC, Vaughn DW, Watts DM, Salas R, Villalobos I, Ramos C and Rico-Hesse R: Dengue virus structural differences that correlate with pathogenesis. J Virol. 73:4738–4747. 1999.PubMed/NCBI
4	Descloux E, Cao-Lormeau VM, Roche C and De Lamballerie X: Dengue 1 diversity and microevolution, French Polynesia 2001–2006: Connection with epidemiology and clinics. PLoS Negl Trop Dis. 3:e4932009. View Article : Google Scholar
5	Halstead SB: Dengue in the Americas and Southeast Asia: Do they differ? Rev Panam Salud Publica. 20:407–415. 2006. View Article : Google Scholar
6	Rico-Hesse R, Harrison LM, Salas RA, Tovar D, Nisalak A, Ramos C, Boshell J, de Mesa MT, Nogueira RM and da Rosa AT: Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology. 230:244–251. 1997. View Article : Google Scholar : PubMed/NCBI
7	Diamond MS: Evasion of innate and adaptive immunity by flaviviruses. Immunol Cell Biol. 81:196–206. 2003. View Article : Google Scholar : PubMed/NCBI
8	Hapuarachchi HC, Koo C, Kek R, Xu H, Lai YL, Liu L, Kok SY, Shi Y, Chuen RL, Lee KS, et al: Intra-epidemic evolutionary dynamics of a Dengue virus type 1 population reveal mutant spectra that correlate with disease transmission. Sci Rep. 6:225922016. View Article : Google Scholar : PubMed/NCBI
9	Maher-Sturgess SL, Forrester NL, Wayper PJ, Gould EA, Hall RA, Barnard RT and Gibbs MJ: Universal primers that amplify RNA from all three flavivirus subgroups. Virol J. 5:162008. View Article : Google Scholar : PubMed/NCBI
10	Kumar S, Stecher G and Tamura K: MEGA7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol. 33:1870–1874. 2016. View Article : Google Scholar : PubMed/NCBI
11	Roy A, Kucukural A and Zhang Y: I-TASSER: A unified platform for automated protein structure and function prediction. Nat Protoc. 5:725–738. 2010. View Article : Google Scholar : PubMed/NCBI
12	Yap TL, Xu T, Chen YL, Malet H, Egloff MP, Canard B, Vasudevan SG and Lescar J: Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution. J Virol. 81:4753–4765. 2007. View Article : Google Scholar : PubMed/NCBI
13	Davis IW, Leaver-Fay A, Chen VB, Block JN, Kapral GJ, Wang X, Murray LW, Arendall WB III, Snoeyink J, Richardson JS and Richardson DC: MolProbity: All-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35:W375–W383. 2007. View Article : Google Scholar : PubMed/NCBI
14	Chen VB, Arendall WB III, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, Murray LW, Richardson JS and Richardson DC: MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr. 66:12–21. 2010. View Article : Google Scholar : PubMed/NCBI
15	Chen VB, Davis IW and Richardson DC: KING (Kinemage, Next Generation): A versatile interactive molecular and scientific visualization program. Protein Sci. 18:2403–2409. 2009. View Article : Google Scholar : PubMed/NCBI
16	Suhre K and Sanejouand YH: On the potential of normal-mode analysis for solving difficult molecular-replacement problems. Acta Crystallogr D Biol Crystallogr. 60:796–799. 2004. View Article : Google Scholar : PubMed/NCBI
17	Quadt-Akabayov SR, Chill JH, Levy R, Kessler N and Anglister J: Determination of the human type I interferon receptor binding site on human interferon-alpha2 by cross saturation and an NMR-based model of the complex. Protein Sci. 15:2656–2668. 2006. View Article : Google Scholar : PubMed/NCBI
18	Williams NK, Bamert RS, Patel O, Wang C, Walden PM, Wilks AF, Fantino E, Rossjohn J and Lucet IS: Dissecting specificity in the Janus kinases: The structures of JAK-specific inhibitors complexed to the JAK1 and JAK2 protein tyrosine kinase domains. J Mol Biol. 387:219–232. 2009. View Article : Google Scholar : PubMed/NCBI
19	Samanta U and Bahnson BJ: Crystal structure of human plasma platelet-activating factor acetylhydrolase: Structural implication to lipoprotein binding and catalysis. J Biol Chem. 283:31617–31624. 2008. View Article : Google Scholar : PubMed/NCBI
20	Mao X, Ren Z, Parker GN, Sondermann H, Pastorello MA, Wang W, McMurray JS, Demeler B, Darnell JE Jr and Chen X: Structural bases of unphosphorylated STAT1 association and receptor binding. Mol Cell. 17:761–771. 2005. View Article : Google Scholar : PubMed/NCBI
21	Yang J, Doyle M, Faulk T, Visentin G, Aster R and Edwards B: Crystal structure of platelet factor 4 mutant 2: Full wwPDB X-ray Structure Validation Report. Sept 27–2017, http://files.rcsb.org/pub/pdb/validation_reports/f9/1f9q/1f9q_full_validation.pdf.
22	Priestle JP, Schär HP and Grütter MG: Crystallographic refinement of interleukin 1 beta at 2.0 Aresolution. Proc Natl Acad Sci USA. 86:9667–9671. 1989. View Article : Google Scholar
23	Somers W, Stahl M and Seehra JS: 1.9 Acrystal structure of interleukin 6: Implications for a novel mode of receptor dimerization and signaling. EMBO J. 16:989–997. 1997. View Article : Google Scholar : PubMed/NCBI
24	Tovchigrechko A and Vakser IA: GRAMM-X public web server for protein-protein docking. Nucleic Acids Res. 34:W310–W314. 2006. View Article : Google Scholar : PubMed/NCBI
25	Tovchigrechko A and Vakser IA: Development and testing of an automated approach to protein docking. Proteins. 60:296–301. 2005. View Article : Google Scholar : PubMed/NCBI
26	Kozakov D, Hall DR, Beglov D, Brenke R, Comeau SR, Shen Y, Li K, Zheng J, Vakili P, Paschalidis ICh and Vajda S: Achieving reliability and high accuracy in automated protein docking: Cluspro, PIPER, SDU, and stability analysis in CAPRI rounds 13-19. Proteins. 78:3124–3130. 2010. View Article : Google Scholar : PubMed/NCBI
27	Kozakov D, Brenke R, Comeau SR and Vajda S: PIPER: An FFT-based protein docking program with pairwise potentials. Proteins. 65:392–406. 2006. View Article : Google Scholar : PubMed/NCBI
28	Comeau SR, Gatchell DW, Vajda S and Camacho CJ: ClusPro: An automated docking and discrimination method for the prediction of protein complexes. Bioinformatics. 20:45–50. 2004. View Article : Google Scholar
29	Yung CF, Lee KS, Thein TL, Tan LK, Gan VC, Wong JG, Lye DC, Ng LC and Leo YS: Dengue serotype-specific differences in clinical manifestation, laboratory parameters and risk of severe disease in adults, Singapore. Am J Trop Med Hyg. 92:999–1005. 2015. View Article : Google Scholar : PubMed/NCBI
30	Zulkarnain E, Hotta S and Takegami T: Molecular comparison of dengue type 1 Mochizuki strain virus and other selected viruses concerning nucleotide and amino acid sequences of genomic RNA: A consideration of viral epidemiology and variation. Microbiol Immunol. 38:581–585. 1994. View Article : Google Scholar : PubMed/NCBI
31	Ishak H, Takegami T, Kamimura K and Funada H: Comparative sequences of two type 1 dengue virus strains possessing different growth characteristics in vitro. Microbiol Immunol. 45:327–331. 2001. View Article : Google Scholar : PubMed/NCBI
32	Park GS, Morris KL, Hallett RG, Bloom ME and Best SM: Identification of residues critical for the interferon antagonist function of Langat virus NS5 reveals a role for the RNA-dependent RNA polymerase domain. J Virol. 81:6936–6946. 2007. View Article : Google Scholar : PubMed/NCBI
33	Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Ashour J, Shupert WL, Holbrook MR, Barrett AD, et al: The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 84:3503–3515. 2010. View Article : Google Scholar : PubMed/NCBI
34	Wang J, Chen S, Liao Y, Zhang E, Feng S, Yu S, Li LF, He WR, Li Y, Luo Y, et al: Mitogen-Activated Protein Kinase Kinase 2, a Novel E2-interacting protein, promotes the growth of classical swine fever virus via attenuation of the JAK-STAT signaling pathway. J Virol. 90:10271–10283. 2016. View Article : Google Scholar :
35	Chiappelli F, Santos SM, Caldeira Brant XM, Bakhordarian A, Thames AD, Maida CA, Du AM, Jan AL, Nahcivan M, Nguyen MT and Sama N: Viral immune evasion in dengue: Toward evidence-based revisions of clinical practice guidelines. Bioinformation. 10:726–733. 2014. View Article : Google Scholar
36	Díaz FJ, Black WC IV, Farfán-Ale JA, Loroño-Pino MA, Olson KE and Beaty BJ: Dengue virus circulation and evolution in Mexico: A phylogenetic perspective. Arch Med Res. 37:760–773. 2006. View Article : Google Scholar : PubMed/NCBI
37	Espinoza-Gómez F, López-Lemus AU, Rodriguez-Sanchez IP, Martinez-Fierro ML, Newton-Sánchez OA, Chávez-Flores E and Delgado-Enciso I: Detection of sequences from a potentially novel strain of cell fusing agent virus in Mexican Stegomyia (Aedes) aegypti mosquitoes. Arch Virol. 156:1263–1267. 2011. View Article : Google Scholar : PubMed/NCBI