A 44-Nucleotide Region in the Chikungunya Virus 3' UTR Dictates Viral Fitness in Disparate Host Cells

Viruses. 2024 May 28;16(6):861. doi: 10.3390/v16060861.

Abstract

We previously reported that deletion of a 44-nucleotide element in the 3' untranslated region (UTR) of the Chikungunya virus (CHIKV) genome enhances the virulence of CHIKV infection in mice. Here, we find that while this 44-nucleotide deletion enhances CHIKV fitness in murine embryonic fibroblasts in a manner independent of the type I interferon response, the same mutation decreases viral fitness in C6/36 mosquito cells. Further, the fitness advantage conferred by the UTR deletion in mammalian cells is maintained in vivo in a mouse model of CHIKV dissemination. Finally, SHAPE-MaP analysis of the CHIKV 3' UTR revealed this 44-nucleotide element forms a distinctive two-stem-loop structure that is ablated in the mutant 3' UTR without altering additional 3' UTR RNA secondary structures.

Keywords: 3′ UTR; CHIKV; Chikungunya virus; RNA structure; SHAPE-MaP; viral fitness.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions*
  • Animals
  • Cell Line
  • Chikungunya Fever* / virology
  • Chikungunya virus* / genetics
  • Chikungunya virus* / physiology
  • Disease Models, Animal
  • Fibroblasts / virology
  • Genetic Fitness
  • Humans
  • Mice
  • Nucleic Acid Conformation
  • RNA, Viral / genetics
  • Sequence Deletion
  • Virulence
  • Virus Replication*

Substances

  • 3' Untranslated Regions
  • RNA, Viral