MUTATIONAL DYNAMICS AND EVOLUTION OF ZOONOTIC RNA VIRUSES IN NATURAL RESERVOIRS

The emergence of zoonotic RNA viruses poses a critical threat to global public health, with approximately 75% of new infectious diseases originating from animal reservoirs. While global evolutionary trends are well- documented, the intersection of viral mutational dynamics and regional ecological factors - particularly in Central Asia remains insufficiently integrated, hindering effective biosafety surveillance. This review follows the PRISMA guidelines, synthesizing molecular-genetic data from PubMed, Web of Science, and Scopus to analyze the mutational plasticity of RNA viruses and their circulation in natural reservoirs. Our analysis characterizes the molecular drivers of interspecies barriers and demonstrates that Kazakhstan’s unique biogeographic landscape acts as a catalyst for region-specific viral evolution. We conclude that integrating «One Health» frameworks with metagenomic surveillance is essential to mitigate future zoonotic risks in the region.

1. Taylor, L. H., Latham, S. M., & Woolhouse, M. E. (2001). Risk factors for human disease emergence. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 356(1411), 983–989. https://doi.org/10.1098/rstb.2001.0888

2. Jones, K. E., Patel, N. G., Levy, M. A., Storeygard, A., & Balk, D. (2008). Global trends in emerging infectious diseases. Nature, 451(7181), 990–993. https://doi.org/10.1038/nature06536

3. Pandit, P. S., Anthony, S. J., Goldstein, T., Olival, K. J., & Doyle, M. M. (2022). Predicting the potential for zoonotic transmission and host associations for novel viruses. Communications Biology, 5(1), 844. https://doi.org/10.1038/s42003-022-04364-y

4. Ellwanger, J. H., & Chies, J. A. B. (2021). Zoonotic spillover: Understanding basic aspects for better prevention. Genetics and Molecular Biology, 44(1 Suppl 1), e20200425. https://doi.org/10.1590/1678-4685-GMB-2020-0425

5. Parrish, C. R., Holmes, E. C., Morens, D. M., & Park, E. C. (2008). Cross-species virus transmission and the emergence of new epidemic diseases. Microbiology and Molecular Biology Reviews, 72(3), 457–470. https://doi.org/10.1128/MMBR.00004-08

6. Mandary, M. B., Masomian, M., & Poh, C. L. (2019). Impact of RNA virus evolution on quasispecies formation and virulence. International Journal of Molecular Sciences, 20(18), 4657. https://doi.org/10.3390/ijms20184657

7. Fairman, C. W., Lever, A. M. L., & Kenyon, J. C. (2021). Evaluating RNA structural flexibility: Viruses lead the way. Viruses, 13(11), 2130. https://doi.org/10.3390/v13112130

8. Villa, T. G., Abril, A. G., Sánchez, S., de Miguel, T., & Sánchez-Pérez, A. (2021). Animal and human RNA viruses: genetic variability and ability to overcome vaccines. Archives of Microbiology, 203(2), 443–464. https://doi.org/10.1007/s00203-020-02040-5

9. Peck, K. M., & Lauring, A. S. (2018). Complexities of Viral Mutation Rates. Journal of Virology, 92(14), e01031-17. https://doi.org/10.1128/JVI.01031-17

10. . Burashev, Ye. D., Orynbayev, M. B., Sultankulova, K. T., Omarova, Z. D., Tulendibayev, A. B., Argimbayeva, T. U., Aubakir, N. A., & Yermekbay, T. T. (2024). Monitoring the spread of avian influenza virus in Kazakhstan. Agrarian Science, (12), 41-44. https://doi.org/10.32634/0869-8155-2024-389-12-41-44

11. Kabzhanova, A. M., Mukhanbetkaliyev, Y. Y., Yesembekova, G. N., Berdikulov, M. A., & Abdrakhmanov, S. K. (2022). Spatiotemporal analysis of the epizootic situation of animal rabies in Kazakhstan. Bulletin of Science of S. Seifullin Kazakh Agrotechnical University, 3(114), 51–58. https://doi.org/10.51452/kazatu.2022.3(114).1118

12. Agranovsky, A. A. (2021). Structure and expression of large (+)RNA genomes of viruses of higher eukaryotes. Biochemistry (Moscow), 86(3), 248–261. https://doi.org/10.1134/S0006297921030020

13. Mittelholzer, C., & Klimkait, T. (2022). Advances in molecular genetics enabling studies of highly pathogenic RNA viruses. Viruses, 14(12), 2682. https://doi.org/10.3390/v14122682

14. Černý, J., Bolfíková, B. Č., Valdés, J. J., Grubhoffer, L., & Růžek, D. (2014). Evolution of Tertiary Structure of Viral RNA Dependent Polymerases. PLoS ONE, 9(5), e96070. https://doi.org/10.1371/journal.pone.0096070

15. Denison, M. R., Graham, R. L., Donaldson, E. F., Eckerle, L. D., & Baric, R. S. (2011). Coronaviruses: an RNA proofreading machine. Nature Reviews Microbiology, 9(4), 263-274. https://doi.org/10.1038/nrmicro2572

16. Brook, C. E., Shoemaker, T., Bundgaard, I., et al. (2020). Accelerated viral dynamics in bat cell lines, with implications for zoonotic disease severity. eLife, 9, e48480. https://doi.org/10.7554/eLife.48480

17. Sanjuán, R., & Domingo-Calap, P. (2016). Mechanisms of viral mutation. Cellular and Molecular Life Sciences, 73(23), 4433-4448. https://doi.org/10.1007/s00018-016-2299-6

18. . Kawasaki, Y., et al. (2023). Comparison of genome replication fidelity between SARS-CoV-2 and influenza A virus in human cells. Scientific Reports, 13, 13278. https://doi.org/10.1038/s41598-023-40463-4

19. Robson, F., Khan, K. S., Le, T. K., et al. (2020). Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting. Molecular Cell, 79(5), 710–727. https://doi.org/10.1016/j.molcel.2020.07.027

20. Dolan, P. T., Whitfield, Z. J., & Andino, R. (2018). Mechanisms and concepts in RNA virus population dynamics and evolution. Annual Review of Virology, 5(1), 69–92. https://doi.org/ 10.1146/annurev-virology-101416-041718

21. Dash, M., Meher, P., Aditya, K., Satapathy, S. S., & Namsa, N. D. (2024). High frequency of transition to transversion ratio in the stem region of RNA secondary structure of untranslated region of SARS-CoV-2. PeerJ, 12, e16962. https://doi.org/10.7717/peerj.16962

22. Te Velthuis, A. J. W., Grimes, J. M., & Fodor, E. (2021). Structural insights into RNA polymerases of negative-sense RNA viruses. Nature Reviews Microbiology, 19(5), 303–318. https://doi.org/10.1038/s41579-020-00501-8

23. Gortazar, C., Reperant, L. A., Kuiken, T., de la Fuente, J., & Boadella, M. (2014). Crossing the interspecies barrier: Opening the door to zoonotic pathogens. PLoS Pathogens, 10(6), e1004129. https://doi.org/10.1371/journal.ppat.1004129

24. Wells, K., & Clark, N. J. (2019). Host specificity in variable environments. Trends in Parasitology, 35(6), 452–465. https://doi.org/10.1016/j.pt.2019.04.001

25. . Herfst, S., Böhringer, M., Karo, B., Lawrence, P., & Lewis, N. S. (2017). Drivers of airborne human-to-human pathogen transmission. Current Opinion in Virology, 22, 22–29. https://doi.org/10.1016/j.coviro.2016.11.006

26. Plowright, R. K., & Hudson, P. J. (2021). From protein to pandemic: The transdisciplinary approach needed to prevent spillover and the next pandemic. Viruses, 13(7), 1298. https://doi.org/10.3390/v13071298

27. Harrison, S. C. (2015). Viral membrane fusion. Virology, 479-480, 498–507. https://doi.org/10.1016/j.virol.2015.03.043

28. Escudero-Pérez, B., Lalande, A., Mathieu, C., & Lawrence, P. (2023). Host-pathogen interactions influencing zoonotic spillover potential and transmission in humans. Viruses, 15(3), 599. https://doi.org/10.3390/v15030599

29. Priyadarsini, S. L., Suresh, M., & Huisingh, D. (2020). What can we learn from previous pandemics to reduce the frequency of emerging infectious diseases like COVID-19? Global Transitions, 2, 202–220. https://doi.org/10.1016/j.glt.2020.09.003

30. Jackson, C. B., Farzan, M., Chen, B., & Choe, H. (2022). Mechanisms of SARS-CoV-2 entry into cells. Nature Reviews Molecular Cell Biology, 23(1), 3–20. https://doi.org/10.1038/s41580-021-00418-x

31. Smith, H. A., Chakraborty, S., Gooley, P. R., Moseley, G. W., & Rawlinson, S. M. (2025). New directions in the multifunctionality of RNA viruses: insights from the rabies virus P-protein. Current Opinion in Virology, 73, 101496. https://doi.org/10.1016/j.coviro.2025.101496

32. Aditi, S., & Shariff, M. (2019). Nipah virus infection: A review. Epidemiology and Infection, 147, e95. https://doi.org/10.1017/S0950268819000086

33. Ang, B. S. P., Lim, T. C. C., & Wang, L. (2018). Nipah Virus Infection. Journal of Clinical Microbiology, 56(6), e01875-17. https://doi.org/ 10.1128/JCM.01875-17

34. Bi, Y., Yang, J., Wang, L., Ran, L., & Gao, G. F. (2024). Ecology and evolution of avian influenza viruses. Current Biology, 34(15), R716–R721. https://doi.org/10.1016/j.cub.2024.05.053

35. Reperant, L. A., Kuiken, T., & Osterhaus, A. D. (2012). Influenza viruses: from birds to humans. Human Vaccines & Immunotherapeutics, 8(1), 7–16. https://doi.org/10.4161/hv.8.1.18672

36. World Organisation for Animal Health (WOAH). (2009). Sub-Regional Meeting on Zoonoses in Central Asia. Astana (Kazakhstan), 17-19 November 2009. WOAH Publications.

37. Zhou, S., Liu, B., Han, Y., Wang, Y., Chen, L., Wu, Z., & Yang, J. (2022). ZOVER: the database of zoonotic and vector-borne viruses. Nucleic Acids Research, 50(D1), D943–D949. https://doi.org/10.1093/nar/gkab862

38. Sultankulova, K. T., Shynybekova, G. O., Kozhabergenov, N. S., Mukhami, N. N., & Chervyakova, O. V. (2022). The Prevalence and Genetic Variants of the CCHF Virus Circulating among Ticks in the Southern Regions of Kazakhstan. Pathogens, 11(8), 841. https://doi.org/10.3390/pathogens11080841

39. Abdiyeva, K., Turebekov, N., Yegemberdiyeva, R., Dmitrovskiy, A., & Yeraliyeva, L. (2020). Vectors, molecular epidemiology and phylogeny of TBEV in Kazakhstan and Central Asia. Parasites & Vectors, 13(1), 504. https://doi.org/10.1186/s13071-020-04362-1

40. Sultankulova, K. T., Kozhabergenov, N. S., Shynybekova, G. O., Chervyakova, O. V., & Usserbayev, B. S. (2025). Metagenomic detection of RNA viruses of Hyalomma asiaticum ticks in the southern regions of Kazakhstan. Microorganisms, 13(9), 2064. https://doi.org/10.3390/microorganisms13092064

41. Jia, Y., Wang, S., Yang, M., Ulzhan, N., Omarova, K., Liu, Z., Kazkhan, O., & Wang, Y. (2022). First detection of tacheng tick virus 2 in hard ticks from southeastern Kazakhstan. Kafkas Universitesi Veteriner Fakultesi Dergisi, 28(1), 139–142. https://doi.org/10.9775/kvfd.2021.26453

42. Usserbayev B., et al. (2025). Genetic Variations of Three Kazakhstan Strains of the SARS-CoV-2 Virus. Viruses, 17(3), 415. https://doi.org/10.3390/v17030415

43. Kassenov M., et al. (2023).Complete Coding Sequence of a Lineage AY.122 SARS-CoV-2 Virus Strain Detected in Kazakhstan. Microbiology Resource Announcements, 12(7), e00353-23.

44. https://doi.org/10.1128/mra.00353-23

45. Berdikulov M., et al. (2025). Molecular and phylogenetic characterization of Crimean-Congo hemorrhagic fever virus circulating in Kazakhstan. Frontiers in Veterinary Science, 12, 1623822.

46. https://doi.org/10.3389/fvets.2025.1623822

47. Volynkina A., et al. (2022). Molecular epidemiology and phylogeography of Crimean-Congo hemorrhagic fever virus. PLOS ONE,17(4), e0266177. https://doi.org/10.1371/journal.pone.0266177

48. Mendenhall I.H., et al. (2029). Discovery and Characterization of Novel Bat Coronavirus Sequences from Kazakhstan. Viruses, 11(4), 356. https://doi.org/10.3390/v11040356