Characterization of a murine model of non-lethal, symptomatic dengue virus infection

Sci Rep. 2018 Mar 20;8(1):4900. doi: 10.1038/s41598-018-22618-w.

Abstract

The mosquito-borne disease dengue is caused by four serologically- and genetically-related viruses, termed DENV-1 to DENV-4. Historical setbacks due to lack of human-like mouse models of dengue were partially remedied with characterization of lethal DENV-2 infection in immunocompromised AG129 mice (deficient in IFN-α/β/γ receptors). Recently, our group established lethal AG129 mouse infection models of DENV-1, DENV-3, and DENV-4 using human isolates. Here we compare a non-lethal, disseminated model of DENV-3 infection using strain D83-144 to that of the lethal outcome following infection by strain C0360/94. Both strains belong to DENV-3 genotype II and differ by only 13 amino acids. Intraperitoneal inoculation of AG129 mice with strain D83-144 led to clinical signs of dengue infection, such as cytokine induction, thrombocytopenia, and systemic infection. However, C0360/94 infection led to features of severe human dengue, including coagulopathy and lethal outcome, whereas D83-144 infection does not. This study is the first to investigate a low passage, non-mouse lethal strain in AG129 mice and demonstrates that D83-144 infection induces milder features of human dengue than those induced by lethal C0360/94 infection. The results suggest that the AG129 mouse model has applications to investigate factors associated with mild or severe disease.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Dengue / physiopathology*
  • Dengue / virology
  • Dengue Virus / physiology*
  • Disease Models, Animal*
  • Disseminated Intravascular Coagulation
  • Female
  • Genotype*
  • Humans
  • Immunocompromised Host
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Transgenic
  • RNA, Viral / genetics*
  • Receptors, Interferon / deficiency
  • Serogroup
  • Thrombocytopenia

Substances

  • Cytokines
  • RNA, Viral
  • Receptors, Interferon