Design and testing of Hepatitis Delta Ribozymes for suppression of Chikungunya virus infection in cell cultures
Main Article Content
Abstract
Chikungunya virus is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates following the introduction of its major vector, Aedes albopictus. Recent cases have been documented in Europe, the Caribbean, and the Americas. Chikungunya virus causes a disease frequently misdiagnosed as Dengue fever, with potentially life-threatening symptoms that can result in long term debilitating arthritis. There have been ongoing investigations of possible therapeutic interventions for both acute and chronic symptoms, but to date none have proven effective in reducing the severity or lasting effects of this disease. Recently, a promising vaccine candidate has received accelerated approval, indicating the importance of remedies to this emerging worldwide health threat. Nonetheless, therapeutic interventions for Chikungunya and other mosquito borne virus diseases are urgently needed yet remain elusive. The increasing risk of spread from endemic regions via human travel and commerce, coupled with the absence of a vaccine or approved therapeutic, puts a significant proportion of the world population at risk for this disease. In this report we explore the possibility of using Specific On/oFf Adapter Hepatitis Delta Virus Ribozymes as antivirals in cells infected with Chikungunya virus. The results we obtained suggest there could be some role in using these ribozyme molecules as antiviral therapies for not only Chikungunya virus, but potentially other viruses as well.
Keywords:
Chikungunya, CHIKV, Hepatitis Delta, Ribozyme, Antiviral
Article Details
How to Cite
FRASER, Mark E. et al.
Design and testing of Hepatitis Delta Ribozymes for suppression of Chikungunya virus infection in cell cultures.
Medical Research Archives, [S.l.], v. 12, n. 8, sep. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5762>. Date accessed: 04 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i8.5762.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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13. Hochedez P, Hausfater P, Jaureguiberry S, et al. Cases of chikungunya fever imported from the islands of the South West Indian Ocean to Paris, France. Euro Surveill. 2007;12(1):pii=679. 2738459.
14. Morrison TE. Reemergence of chikungunya virus. J Virol. 2014;88(20):11644-7. doi: 10.1128/JVI.01432-14.
15. Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog. 2007;3(12):e201. doi: 10.1371/journal.ppat.0030201.
16. Wang E, Volkova E, Adams AP, Forrester N, Xiao SY, Frolov I, Weaver SC. Chimeric alphavirus vaccine candidates for chikungunya. Vaccine. 2008;26(39):5030-9. doi: 10.1016/j.vaccine.2008.07.054.
17. Kumar M, Sudeep AB, Arankalle VA. Evaluation of recombinant E2 protein-based and whole-virus inactivated candidate vaccines against chikungunya virus. Vaccine. 2012;30(43):6142-9. doi: 10.1016/j.vaccine.2012.07.072. Epub 2012 Aug 8.
18. Wang D, Suhrbier A, Penn-Nicholson A, et al. A complex adenovirus vaccine against chikungunya virus provides complete protection against viraemia and arthritis. Vaccine. 2011;29(15):2803-9. doi: 10.1016/j.vaccine.2011.01.108.
19. Slifka DK, Raué HP, Weber WC, et al. Development of a next-generation chikungunya virus vaccine based on the HydroVax platform. PLoS Pathog. 2022;18(7):e1010695. doi: 10.1371/journal.ppat.1010695.
20. Metz SW, Gardner J, Geertsema C, et al. Effective chikungunya virus-like particle vaccine produced in insect cells. PLoS Negl Trop Dis. 2013;7(3):e2124. doi: 10.1371/journal.pntd.0002124.
21. Livengood JA, Partidos CD, Plante K, et al. Preclinical Evaluation of a Live Attenuated Chikungunya Vaccine, Procedia in Vaccinology. 2012;6:141-149, ISSN 1877-282X, https://doi.org/10.1016/j.provac.2012.04.019.
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23. Schneider M, Narciso-Abraham M, Hadl S, et al. Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2023;401(10394):2138-2147. doi: 10.1016/S0140-6736(23)00641-4.
24. Battisti V, Urban E, Langer T. Antivirals against the Chikungunya Virus. Viruses. 2021;13(7):1307. doi: 10.3390/v13071307.
25. Suzuki Y. Interferon-induced restriction of Chikungunya virus infection. Antiviral Res. 2023 Feb;210:105487. doi: 10.1016/j.antiviral.2022.105487.
26. López LS, Calvo EP, Castellanos JE. Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication. Viruses. 2023;15(2):481. doi: 10.3390/v15020481.
27. Oyewole OO, Dunnavant K, Bhattarai S, et al. A Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infection. Viruses. 2022;14(6):1123. doi: 10.3390/v14061123.
28. Nam S, Ga YJ, Lee JY, Hwang WY, Jung E, Shin JS, Chen W, Choi G, Zhou B, Yeh JY, Go YY. Radicicol Inhibits Chikungunya Virus Replication by Targeting Nonstructural Protein 2. Antimicrob Agents Chemother. 2021;65(7):e0013521. doi: 10.1128/AAC.00135-21.
29. Levi LI, Rezelj VV, Henrion-Lacritick A, et al. Defective viral genomes from chikungunya virus are broad-spectrum antivirals and prevent virus dissemination in mosquitoes. PLoS Pathog. 2021;17(2):e1009110. doi: 10.1371/journal.ppat.1009110.
30. Solignat M, Gay B, Higgs S, Briant L, Devaux C. Replication cycle of chikungunya: a re-emerging arbovirus. Virology. 2009;393(2):183-97. doi: 10.1016/j.virol.2009.07.024. Epub 2009 Sep 4.
31. Dash PK, Tiwari M, Santhosh SR, Parida M, Lakshmana Rao PV. RNA interference mediated inhibition of Chikungunya virus replication in mammalian cells. Biochem Biophys Res Commun. 2008;376(4):718-22. doi: 10.1016/j.bbrc.2008.09.040.
32. Lam S, Chen KC, Ng MM, Chu JJ. Expression of plasmid-based shRNA against the E1 and nsP1 genes effectively silenced Chikungunya virus replication. PLoS One. 2012;7(10):e46396. doi: 10.1371/journal.pone.0046396.
33. Bull JJ, Jacobson A, Badgett MR, Molineux IJ. Viral escape from antisense RNA. Mol Microbiol. 1998;28(4):835-46. doi: 10.1046/j.1365-2958.1998.00847.x.
34. Cheng GF, Lin JJ, Shi Y, et al. Dose-dependent inhibition of gynecophoral canal protein gene expression in vitro in the schistosome (Schistosoma japonicum) by RNA interference. Acta Biochim Biophys Sin (Shanghai). 2005;37(6):386-90. doi: 10.1111/j.1745-7270.2005.00058.x.
35. Parashar D, Paingankar MS, Kumar S, et al. Administration of E2 and NS1 siRNAs inhibit chikungunya virus replication in vitro and protects mice infected with the virus. PLoS Negl Trop Dis. 2013;7(9):e2405. doi: 10.1371/journal.pntd.0002405.
36. von Laer D, Hasselmann S, Hasselmann K. Gene therapy for HIV infection: what does it need to make it work? J Gene Med. 2006;8(6):658-67. doi: 10.1002/jgm.908.
37. Rossi JJ, June CH, Kohn DB. Genetic therapies against HIV. Nat Biotechnol. 2007;25(12):1444-54. doi: 10.1038/nbt1367.
38. Mitsuyasu RT, Merigan TC, Carr A, et al. 2009. Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells. Nat Med. 2009;15(3):285-92. doi: 10.1038/nm.1932.
39. Nawtaisong P, Keith J, Fraser T, et al. Effective suppression of Dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome. Virol J. 2009;6:73. doi: 10.1186/1743-422X-6-73.
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