Analysis of the Function of the Lymphocytic Choriomeningitis Virus S Segment Untranslated Region on Growth Capacity In Vitro and on Virulence In Vivo

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 5&prime
and 3&prime
termini. There are internal UTRs composed of 58 and 41 nucleotide residues in the 5&prime
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&ndash
40 and 20&ndash
38 located downstream of the 19 nucleotides in the 5&prime
termini, respectively, were involved in viral genome replication and transcription. Furthermore, it was revealed that the other internal UTRs (nucleotides 41&ndash
77 and 39&ndash
60 in the 5&prime
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.