ANALISA EVOLUSI VIRUS DENGUE YANG ENDEMIK DI INDONESIA
Article Sidebar
Main Article Content
Abstract
Indonesia merupakan daerah dengan hiperendemisitas tinggi untuk infeksi virus dengue dan tempat bersirkulasinya keempat varian genotype virus dengue. Saat ini salah satu cara untuk pencegahan infeksi virus dengue adalah dengan vaksin dengue yang baru tersedia tahun 2016. Vaksin dengue ini menstimulasi terbentuknya antibodi yang akan mengenali membran dan selubung dari keempat genotipe virus dengue. Efektivitas dari vaksin ini tergantung dari kesesuaian antara antibodi yang terbentuk dengan varian yang beredar di Indonesia. Mengingat virus dengue merupakan virus RNA yang umumnya memiliki laju mutasi yang tinggi, mutasi yang terjadi dapat mengakibatkan terbentuknya escape mutant yang mampu menghindari antibodi yang terbentuk oleh vaksin. Penelitian ini bertujuan untuk mengetahui evolusi dan laju mutasi dari virus dengue yang beredar di Indonesia. Sebanyak 116 data genom lengkap dari virus dengue yang telah dilaporkan di Indonesia digunakan dalam penelitian ini. Genotipe virus dengue dianalisa dengan menggunakan software MEGA-X. Evolusi dan laju mutasi dari gen penyandi selubung (E) dan membran (M) virus dengue dianalisa dengan menggunakan software BEAST versi 1.8.3. Hasil dari penelitian ini menunjukkan gen E dan M virus dengue telah berevolusi semenjak pertama kali dilaporkan pada tahun 1975 dan memiliki laju mutasi yang tinggi. Gen E mencapai 9.26 x 10-4 subsitusi/basa/tahun (95% HPD 7.81 X 10 10-4 – 1.07 X 10-3) maupun gen M yang mencapai 8.5 x 10-4 subsitusi/basa/tahun (95% HPD 6.03 X 10 10-4 – 1.09 X 10-3). Tingginya laju mutasi ini membutuhkan perhatian bagi pengembang vaksin untuk pengawasan dan evaluasi yang berkesinambungan.
Indonesia is an area with high hyperendemicity for dengue virus infection and the circulation of the four variants of dengue virus genotype. Currently, one way to prevent dengue virus infection is with a new dengue vaccine available in 2016. This dengue vaccine stimulates the formation of antibodies that will recognize the membrane and envelope of the four dengue virus genotypes. The effectiveness of this vaccine depends on the suitability of the antibodies formed with variants circulating in Indonesia. Since dengue virus is an RNA virus that generally has a high mutation rate, the mutations that occur can result in the formation of escape mutants that are able to avoid the antibodies formed by the vaccine. This study aims to determine the evolution and mutation rate of dengue viruses circulating in Indonesia. A total of 116 complete genome data from dengue viruses that have been reported in Indonesia were used in this study. Dengue virus genotypes were analyzed using MEGA-X software. The evolution and mutation rate of the envelope (E) and membrane (M) gene of the dengue virus were analyzed using BEAST software version 1.8.3. The results of this study indicate that the E and M genes of the dengue virus have evolved since they were first reported in 1975 and have a high mutation rate. Gen E reaches 9.26 x 10-4 substitution / base / year (95% HPD 7.81 X 10 10-4 - 1.07 X 10-3) and M gene reaches 8.5 x 10-4 substitution / base / year (95% HPD 6.03 X 10 10-4 - 1.09 X 10-3). The high rate of this mutation requires attention for vaccine developers for ongoing monitoring and evaluation.
Article Details
This work is licensed under a Jurnal Muara Sains, Teknologi, Kedokteran dan Ilmu Kesehatan Creative Commons Attribution-ShareAlike 4.0 International License.
Authors transfer copyright or assign exclusive rights to the publisher (including commercial rights)
References
Abbas, A. K., Lichtman, A. H. H., & Pillai, S. (2014). Cellular and Molecular Immunology: with STUDENT CONSULT Online Access. Elsevier Health Sciences.
Agarwal, R., Wahid, M. H., Yausep, O. E., Angel, S. H., & Lokeswara, A. W. (2017). The Immunogenicity and Safety of CYD-Tetravalent Dengue Vaccine (CYD-TDV) in Children and Adolescents: A Systematic Review. Acta Medica Indonesiana, 49(1), 24–33.
Allicock, O. M., Lemey, P., Tatem, A. J., Pybus, O. G., Bennett, S. N., Mueller, B. A., … Carrington, C. V. F. (2012). Phylogeography and Population Dynamics of Dengue Viruses in the Americas. Molecular Biology and Evolution, 29(6), 1533–1543. Retrieved from https://doi.org/10.1093/molbev/msr320
Bouckaert, R., Heled, J., K?hnert, D., Vaughan, T., Wu, C.H., Xie, D., … Drummond, A.J. (2014). Beast 2: A Software for Bayesian Evolutionary Analysis. Plos Computational Biology, 10(4). Retrieved from https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003537
Bhatt, S., Gething, P. W., Brady, O. J., Messina, J. P., Farlow, A. W., Moyes, C. L., … Hay, S. I. (2013). The global distribution and burden of dengue. Nature, 496(7446), 504–507. Retrieved from https://doi.org/10.1038/nature12060
Darriba, D., Taboada, G. L., Doallo, R., & Posada, D. (2012). jModelTest 2: more models, new heuristics and high-performance computing. Nature Methods, 9(8), 772. Retrieved from https://doi.org/10.1038/nmeth.2109
Doud, M. B., Hensley, S. E., & Bloom, J. D. (2017). Complete mapping of viral escape from neutralizing antibodies. PLoS Pathogens, 13(3). Retrieved from https://doi.org/10.1371/journal.ppat.1006271
Fadhila, S. R. (2017). Sekilas tentang Vaksin Dengue. Retrieved from IDAI website http://www.idai.or.id/artikel/klinik/imunisasi/sekilas-tentang-vaksin-dengue
Fahri, S., Yohan, B., Trimarsanto, H., Sayono, S., Hadisaputro, S., Dharmana, E., … Sasmono, R. T. (2013). Molecular surveillance of dengue in Semarang, Indonesia revealed the circulation of an old genotype of dengue virus serotype-1. PLoS Neglected Tropical Diseases, 7(8), e2354. Retrieved from https://doi.org/10.1371/journal.pntd.0002354
Haryanto, S., Hayati, R. F., Yohan, B., Sijabat, L., Sihite, I. F., Fahri, S., … Sasmono, R. T. (2016). The molecular and clinical features of dengue during outbreak in Jambi, Indonesia in 2015. Pathogens and Global Health, 110(3), 119–129. Retrieved from https://doi.org/10.1080/20477724.2016.1184864
Kumar, S., Stecher, G., Li, M., Knyaz, C., & Tamura, K. (2018). MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Molecular Biology and Evolution, 35(6), 1547–1549. Retrieved from https://doi.org/10.1093/molbev/msy096
Megawati, D., Masyeni, S., Yohan, B., Lestarini, A., Hayati, R. F., Meutiawati, F., … Sasmono, R. T. (2017). Dengue in Bali: Clinical characteristics and genetic diversity of circulating dengue viruses. PLoS Neglected Tropical Diseases, 11(5). Retrieved from https://doi.org/10.1371/journal.pntd.0005483
Nusa, R., Prasetyowati, H., Meutiawati, F., Yohan, B., Trimarsanto, H., Setianingsih, T. Y., & Sasmono, R. T. (2014). Molecular surveillance of Dengue in Sukabumi, West Java province, Indonesia. Journal of Infection in Developing Countries, 8(6), 733–741.
Sanjuán, R., Nebot, M. R., Chirico, N., Mansky, L. M., & Belshaw, R. (2010). Viral Mutation Rates. Journal of Virology, 84(19), 9733–9748. Retrieved from https://doi.org/10.1128/JVI.00694-10
Sasmono, R. T., Wahid, I., Trimarsanto, H., Yohan, B., Wahyuni, S., Hertanto, M., … Schreiber, M. J. (2015). Genomic analysis and growth characteristic of dengue viruses from Makassar, Indonesia. Infection, Genetics and Evolution, 32, 165–177. Retrieved from https://doi.org/10.1016/j.meegid.2015.03.006
World Health Organization. (2012). Global Strategy for dengue prevention and control, 2012–2020. Retrieved from WHO website: http://www.who.int/denguecontrol/9789241504034/en/
Ye, Q., Shang, S., & Li, W. (2015). A new vaccine escape mutant of hepatitis B virus causes occult infection. Human Vaccines & Immunotherapeutics, 11(2), 407–410. Retrieved from https://doi.org/10.4161/21645515.2014.994461