Published date: Feb 11 2020

Journal Title: KnE Life Sciences

Issue title: The 2019 International Conference on Biotechnology and Life Sciences (IC-BIOLIS)

Pages:

DOI: 10.18502/kls.v5i2.6439

Rahmat Azhari Kemalrahmat.azharikemal@lecturer.unri.ac.idDepartment of Medical Biology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia

Jeremias IvanDepartment of BioInformatics, School of Life Sciences, Indonesia International Institute for Life Sciences. Pulomas Barat Kav. 88, Jakarta, Indonesia

Eric Bernardus Lili SandjajaDepartment of BioTechnology, School of Life Sciences, Indonesia International Institute for Life Sciences. Pulomas Barat Kav. 88, Jakarta, Indonesia

Audi Putra SantosaDepartment of BioTechnology, School of Life Sciences, Indonesia International Institute for Life Sciences. Pulomas Barat Kav. 88, Jakarta, Indonesia

Dengue is a mosquito-borne viral disease of which incidence has rapidly increased in the last few years. Despite the recent development of a licensed dengue vaccine, safer and more efficacious dengue vaccine still needs to be developed. Dengue virus has four antigenically and genetically distinct serotypes. Ancestral sequence reconstruction (ASR) and consensus sequence (CS) might be able to overcome antigenic distinction between those four serotypes. Envelope (E) protein is responsible for a wide range of dengue virus biological activities. Domain III of the E protein (EDIII) plays a role in receptor binding for viral entry and inducing protective immunity against the dengue virus. We utilised bioinformatics software to computationally design ancestral and consensus sequences of Asian dengue E protein. E protein sequences of 987 DENV strains and 5 outgroups were retrieved from GenBank. We constructed ancestral and consensus sequences for each serotype. For ASR, ancestral sequences were gradually designed to construct ancestral sequence for all serotypes using MEGA X. For CS, all four consensus sequences were directly used to construct consensus sequence for all serotypes using UGENE 1.32. Phylogenetic tree consisting existing dengue sequences as well as ancestral and consensus sequences were visualised using FigTree 1.4.4. All ancestral and consensus sequences were analysed for conserved motifs, especially in domain III region. ASR sequences were closer to the centre of phylogenetic tree branches while consensus sequences were located among natural isolates. Further CD4 T cell immunogenicity prediction on domain III (EDIII) showed that both ASR and consensus EDIII have the two-highest combined immunogenicity scores. These sequences are potential for further in vitro and in vivo studies as dengue vaccine candidate.

Keywords: ancestral sequence, consensus, dengue, envelope protein, vaccine

[1] H. Fahimi, M. Mohammadipour, H. Kashani, F. Parvini, & M. Sadeghizadeh. “Dengue viruses and promising envelope protein domain III-based vaccines,” Appl. Microbiol. Biotechnol., vol. 102, no. 7, pp. 2977-2996, 2018.


[2] S. Hasan, S. F. Jamdar, M. Alalowi, & S. M. Al Ageel Al Beaiji. “Dengue virus: A global human threat: Review of literature,” J. Int. Soc. Prev. Community. Dent., vol. 6, no. 1, p. 1, 2016.


[3] R. T. Sasmono, A. F. Taurel, A. Prayitno, H. Sitompul, B. Yohan, R. F. Hayati, A. Bouckenooghe, S. R. Hadinegoro, J. Nealon. “Dengue virus serotype distribution based on serological evidence in pediatric urban population in Indonesia,” PLoS. Negl. Trop. Dis, vol. 12, no. 6, 2018.


[4] World Health Organization. “Dengue,” Retrieved from http://www.searo.who.int/entity/ vector_borne_tropical_diseases/data/data_factsheet/en/index1.html, 2019.


[5] A. Maula, A. Fuad, & A. Utarini. “Ten-years trend of dengue research in Indonesia and South-east Asian countries: a bibliometric analysis,” Global Health Action, vol. 11, no. 1, p. 1504398, 2018.


[6] Departemen Kesehatan Republik Indonesia, “Profil Kesehatan Indonesia 2014,” Retrieved from http://www.depkes.go.id/resources/download/pusdatin/profil-kesehatan-indonesia/profil-kesehatan- indonesia-2014.pdf, 2014.


[7] Y. S. Tian„Y. Zhou, T. Takagi„ M. Kameoka, & N. Kawashita. “Dengue virus and its inhibitors: A brief review,” Chemical and Pharmaceutical Bulletin, vol. 66, no. 3, pp. 191-206. 2018.


[8] S. Sridhar, A. Luedtke, E. Langevin, M. Zhu, M. Bonaparte, & T. Machabert, S. Savarino, B. Zambrano, A. Moureau, A. Khromava, Z. Moodie, T. Westling, C. Mascareñas, C. Frago, M. Cortés, D. Chansinghakul, F. Noriega, A. Bouckenooghe, J. Chen, S. P. Ng, P. B. Gilbert, S. Gurunathan, C. A. DiazGranados. “Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy,” N. Engl. J. Med., vol. 379, no. 4, pp. 327-340, 2018.


[9] R. Voelker. “Dengue Vaccine Gets the Nod,” JAMA, vol. 321, no. 21, p. 2066, 2019


[10] J. Flipse, M. A. Diosa-Toro, T. E. Hoornweg, D. P. I. van de Pol, S. Urcuqui-Inchima, & J. M. Smit. “Antibody- Dependent Enhancement of Dengue Virus Infection in Primary Human Macrophages; Balancing Higher Fusion against Antiviral Responses,” Scientific Reports, vol. 6, no. 1, 2016.


[11] S. Yasmin & M. Mukerjee. “The Dengue Debacle,” Scientific American, vol. 320, no. 4, pp. 38-47, 2019.


[12] K. Fatima & N. I. Syed. “Dengvaxia controversy: impact on vaccine hesitancy,” J. Glob. Health, vol. 8, no. 2, p. 020312, 2018.


[13] M. McArthur, M. Sztein, & R. Edelman. “Dengue vaccines: recent developments, ongoing challenges and current candidates,” Expert Rev. Vaccines, vol. 12, no. 8, pp. 933-953, 2013.


[14] D. L. N. F. Maeda, M. T. Batista, L. R. Pereira, M. de Jesus Cintra, J. H. Amorim, C. Mathias-Santos, S. A. Pereira, S. B. Boscardin, S. dos Ramos Silva, E. L. Faquim-Mauro, V. B. Silveira, D. B. L. Oliveira, S. A. Johnston, L. C. de Souza Ferreira, & J. F. Rodriguez. “Adjuvant-mediated epitope specificity and enhanced neutralizing activity of antibodies targeting dengue virus envelope protein,” Front. Immunol., vol. 8, p. 1175, 2017.


[15] S. Noisakran, N. Onlamoon, P. Songprakhon, H. Hsiao, K. Chokephaibulkit, & G. Perng. “Cells in Dengue Virus Infection In Vivo,” Advances In Virology, vol. 2010, pp. 1-15, 2010.


[16] C. Y. Chiang, M. H. Huang, C. H. Hsieh, M. Y. Chen, H. H. Liu, J. P. Tsai, Y. S. Li, C. Y. Chang, S. J. Liu, P. Chong, C. H. Leng, & H. W. Chen. “Dengue-1 envelope protein domain III along with PELC and CpG oligodeoxynucleotides synergistically enhances immune responses,” PLoS Negl. Trop. Dis., vol. 6, no. 5, p. e1645, 2012.


[17] S. Sukupolvi-Petty, S. K. Austin, W. E. Purtha, T. Oliphant, G. E. Nybakken, J. J. Schlesinger, J. T. Roehrig, G. D. Gromowski, A. D. Barrett, D. H. Fremont, M. S. Diamond. “Type-and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes,”. J. Virol., vol. 81, no. 23, pp. 12816-12826, 2007.


[18] S. M. Lok, V. Kostyuchenko, G. E. Nybakken, H. A. Holdaway, A. J. Battisti, S. Sukupolvi-Petty, D. Sedlak, D. H. Fremont, P. R. Chipman, J. T. Roehrig, M. S. Diamond, R. J. Kuhn, & M. G. Rossmann. “Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins,” Nat. Struct. Mol. Biol., vol. 15, no. 3, p. 312, 2008.


[19] M. Poggianella, J. L. S. Campos, K. R. Chan, H. C. Tan, M. Bestagno, E. E. Ooi, & O. R. Burrone. “Dengue E protein domain III-based DNA immunisation induces strong antibody responses to all four viral serotypes,” PLoS. Negl. Trop. Dis.,vol. 9, no. 7, 2015.
[20] J. Torresi, G. Ebert, & M. Pellegrini. “Vaccines licensed and in clinical trials for the prevention of dengue,” Hum. Vaccin. Immunother., vol. 13, no. 5, pp. 1059-1072, 2017.


[21] K. P. Burke, S. Munshaw, W. O. Osburn, J. Levine, L. Liu, J. Sidney, A. Sette, S. C. Ray, & A. L. Cox. “Immunogenicity and cross-reactivity of a representative ancestral sequence in hepatitis C virus infection,” J. Immunol., vol. 188, no. 10, pp. 5177-5188, 2012.


[22] M. F. Ducatez, J. Bahl, Y. Griffin, E. Stigger-Rosser, J. Franks, S. Barman, D. Vijaykrishna, A. Webb, Y. Guan, R. G. Webster, G. J. D. Smith, R. J. Webby. “Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development,” Proc. Nat. Acad. Sci., vol. 108, no. 1, pp. 349- 354, 2010.


[23] M. W. Chen, T. J. R. Cheng, Y. Huang, J. T. Jan, S. H. Ma, L. Y. Alice, W. Chi-Huey, & D. D. Ho. “A consensus–hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses,” Proc. Natl. Acad. Sci., vol. 105, no. 36, pp. 13538-13543, 2008.


[24] D. L. Kothe, Y. Li, J. M. Decker, F. Bibollet-Ruche, K. P. Zammit, M. G. Salazar, Y. Chen, Z. Weng, E. A. Weaver, F. Gao, B. F. Haynes, G. M. Shaw, B. T. Korber, B. H. Hahn. “Ancestral and consensus envelope immunogens for HIV-1 subtype C,” Virology, vol. 352, no. 2, pp. 438-449, 2016.


[25] R. Edgar. “MUSCLE: multiple sequence alignment with high accuracy and high throughput,” Nucleic Acids Res., vol. 32, no. 5, pp. 1792-1797, 2004.


[26] S. Kumar, G. Stecher, M. Li, C. Knyaz, & K. Tamura. “MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms,” Mol. Biol. Evol., vol. 35, no. 6, pp. 1547-1549, 2018.


[27] K. Okonechnikov, O. Golosova, & M. Fursov. “Unipro UGENE: a unified bioinformatics toolkit,” Bioinformatics, vol. 28, no.8, pp. 1166-1167, 2012.


[28] A. Rambaut. “FigTree: tree figure drawing tool version 1.4.4,” Available at: http://tree.bio.ed.ac.uk/ software/figtree, 2012.


[29] S. Dhanda, E. Karosiene, L. Edwards, A. Grifoni, S. Paul, M. Andreatta, D. Weiskopf, J. Sidney, M. Nielsen, B. Peters, & A. Sette. “Predicting HLA CD4 Immunogenicity in Human Populations,” Front. Immunol., vol. 9, p. 1369, 2018.


[30] S. Paul, C. S. Lindestam Arlehamn, T. J. Scriba, M. B. Dillon, C. Oseroff, D. Hinz, D. M. McKinney, S. C. Pro, J. Sidney, B. Peters, & A. Sette. “Development and validation of a broad scheme for prediction of HLA class II restricted T cell epitopes,” J. Immunol. Methods., vol. 422, pp. 28-34, 2015.


[31] V. Risso, J. Gavira, D. Mejia-Carmona, E. Gaucher, & J. Sanchez-Ruiz. “Hyperstability and Substrate Promiscuity in Laboratory Resurrections of Precambrian β-Lactamases,” J. Am. Chem. Soc., vol. 135, no. 8, pp. 2899-2902, 2013


[32] J. B. Joy, R. H. Liang, R. M. McCloskey, T. Nguyen, & A. F. Y. Poon. “Ancestral Reconstruction,” PLoS. Comput. Biol., vol. 12, no. 7, p. e1004763, 2016.


[33] G. S. Kesturu, Colleton, B. A. Colleton, Y. Liu, L. Heath, O. S. Shaikh, C. R. Jr. Rinaldo, & R. Shankarappa. “Minimization of genetic distances by the consensus, ancestral, and center-of-tree (COT) sequences for HIV-1 variants within an infected individual and the design of reagents to test immune reactivity,” Virology, vol. 348, no. 2, pp. 437-448, 2006.


[34] H. Ross, D. Nickle, Y. Liu, L. Heath, M. Jensen, A. Rodrigo, & J. Mullins. “Sources of Variation in Ancestral Sequence Reconstruction for HIV-1 Envelope Genes,” Evol. Bioinformatics, vol. 2, 2007.


[35] T. Schneider. “Consensus Sequence Zen,” Appl. Bioinformatics, vol. 1, no. 3, pp. 111119, 2002.


[36] X. Q. Li, L. W. Qiu, Y. Chen, K. Wen, J. P. Cai, J. Chen, Y. X. Pan, J. Li, D. M. Hu, Y. F. Huang, L. D. Liu, X. X. Ding, Y. H. Guo, & X. Y. Che. “Dengue virus envelope domain III immunization elicits predominantly cross-reactive, poorly neutralizing antibodies localized to the AB loop: implications for dengue vaccine design,” J. Gen. Virol., vol. 94, no. 10, pp. 2191-2201, 2013.


[37] Y. Lin, K. Wen, Y. Guo, L. Qiu, Y. Pan, L. Yu, B. Di, & Y. Chen. “Mapping of the B cell neutralizing epitopes on ED III of envelope protein from Dengue virus,” Bing Du Xue Bao (Chinese Journal of Virology), vol. 31, no. 6, pp. 665-673, 2015.


[38] C. M. Midgley, A. Flanagan, H. B. Tran, W. Dejnirattisai, K. Chawansuntati, A. Jumnainsong, W. Wongwiwat, T. Duangchinda, J. Mongkolsapaya, J. M. Grimes, G. R. Screaton. A. “Structural Analysis of a Dengue Cross-Reactive Antibody Complexed with Envelope Domain III Reveals the Molecular Basis of Cross-Reactivity,” J. Immunol. vol. 188, no. 10, pp. 4971-4979, 2012.