A natural variation in the RNA polymerase of severe fever with thrombocytopenia syndrome virus enhances viral replication and in vivo virulence

Kyeongseok Jeon, Hyo Jin Ro, Jun Gu Kang, Da Eun Jeong, Joowan Kim, Yebeen Lee, Ga Yeon Yoon, Ju Il Kang, Joon Yong Bae, Jin Il Kim, Man Seong Park, Keun Hwa Lee, Hyun Soo Cho, Yuri Kim, Nam Hyuk Cho

Research output: Contribution to journalArticlepeer-review

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with high mortality in Eastern Asia. The disease is caused by the SFTS virus (SFTSV), also known as Dabie bandavirus, which has a segmented RNA genome consisting of L, M, and S segments. Previous studies have suggested differential viral virulence depending on the genotypes of SFTSV; however, the critical viral factor involved in the differential viral virulence is unknown. Here, we found a significant difference in viral replication in vitro and virulence in vivo between two Korean isolates belonging to the F and B genotypes, respectively. By generating viral reassortants using the two viral strains, we demonstrated that the L segment, which encodes viral RNA-dependent RNA polymerase (RdRp), is responsible for the enhanced viral replication and virulence. Comparison of amino acid sequences and viral replication rates revealed a point variation, E251K, on the surface of RdRp to be the most significant determinant for the enhanced viral replication rate and in vivo virulence. The effect of the variation was further confirmed using recombinant SFTSV generated by reverse genetic engineering. Therefore, our results indicate that natural variations affecting the viral replicase activity could significantly contribute to the viral virulence of SFTSV.

Original languageEnglish
Article numbere29099
JournalJournal of Medical Virology
Volume95
Issue number9
DOIs
Publication statusPublished - 2023 Sept

Bibliographical note

Funding Information:
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare (grant no. HV22C0009) and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2021M3A9I2080489 and 2021M3A9I2080490), Republic of Korea. K. J., H.‐J. R., J. K., and Y.‐B. L. received a scholarship from the BK21‐plus education program provided by the NRF of Korea.

Publisher Copyright:
© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.

Keywords

  • RNA-dependent RNA polymerase
  • genotype
  • reverse genetics
  • severe fever with thrombocytopenia syndrome virus
  • viral replication
  • virulence

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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