Visualization of chikungunya virus infection in vitro and in vivo

Emerg Microbes Infect. 2019;8(1):1574-1583. doi: 10.1080/22221751.2019.1682948.

Abstract

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has become an important re-emerging pathogen with its rapid spread to many non-endemic areas. The lack of effective vaccines and antiviral agents is largely attributed to the elusive infection and dissemination dynamics in vivo. In this study, we designed and developed a novel, replication-competent, CHIKV reporter virus (CHIKV-iRFP) encoding a near infrared fluorescent protein (iRFP). In vitro and in vivo characterization demonstrated that CHIKV-iRFP retained similar replication and virulence phenotypes to its parental virus. Neonatal BABL/c mice and IFNAR-/- A129 mice were highly susceptible to CHIKV-iRFP infection. Following intracranial (i.c.) inoculation, CHIKV-iRFP efficiently replicated and disseminated into whole body, resulting in rapid death in an age-dependent manner. Remarkably, upon footpad injection, CHIKV-iRFP readily disseminated from footpad to head and whole skeleton, with a specific tropism for bone marrow. Taken together, this novel reporter virus provides a powerful tool to track real time CHIKV replication and to test the in vivo efficacy of vaccines and antiviral therapeutics.

Keywords: Chikungunya virus; iRFP; live imaging; mice; reporter virus.

MeSH terms

  • Animals
  • Chikungunya Fever / virology*
  • Chikungunya virus / genetics
  • Chikungunya virus / pathogenicity
  • Chikungunya virus / physiology*
  • Female
  • Fluorescence
  • Genes, Reporter
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Virulence
  • Virus Replication

Substances

  • Luminescent Proteins

Grants and funding

This work was supported by the National Key R&D Program of China (2018YFA0507201) and the National Natural Science Foundation of China (grant number 81572003).