Analysis of the function of the lymphocytic choriomeningitis virus s segment untranslated region on growth capacity in vitro and on virulence in vivo

Satoshi Taniguchi, Tomoki Yoshikawa, Masayuki Shimojima, Shuetsu Fukushi, Takeshi Kurosu, Hideki Tani, Aiko Fukuma, Fumihiro Kato, Eri Nakayama, Takahiro Maeki, Shigeru Tajima, Chang Kweng Lim, Hideki Ebihara, Shigeru Kyuwa, Shigeru Morikawa, Masayuki Saijo

Research output: Contribution to journalArticlepeer-review

Abstract

Lymphocytic choriomeningitis virus (LCMV) is a prototypic arenavirus. The function of untranslated regions (UTRs) of the LCMV genome has not been well studied except for the extreme 19 nucleotide residues of both the 50 and 30 termini. There are internal UTRs composed of 58 and 41 nucleotide residues in the 50 and 30 UTRs, respectively, in the LCMV S segment. Their functional roles have yet to be elucidated. In this study, reverse genetics and minigenome systems were established for LCMV strain WE and the function of these regions were analyzed. It was revealed that nucleotides 20-40 and 20-38 located downstream of the 19 nucleotides in the 50 and 30 termini, respectively, were involved in viral genome replication and transcription. Furthermore, it was revealed that the other internal UTRs (nucleotides 41-77 and 39-60 in the 50 and 30 termini, respectively) in the S segment were involved in virulence in vivo, even though these regions did not affect viral growth capacity in Vero cells. The introduction of LCMV with mutations in these regions attenuates the virus and may enable the production of LCMV vaccine candidates.

Original languageEnglish (US)
Article numberv12080896
JournalViruses
Volume12
Issue number8
DOIs
StatePublished - Aug 2020

Keywords

  • Arenavirus
  • LCMV strain WE
  • Lymphocytic choriomeningitis virus
  • Reverse genetics
  • Untranslated region

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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