Dicer-2 Regulates Resistance and Maintains Homeostasis against Zika Virus Infection in Drosophila

J Immunol. 2018 Nov 15;201(10):3058-3072. doi: 10.4049/jimmunol.1800597. Epub 2018 Oct 10.

Abstract

Zika virus (ZIKV) outbreaks pose a massive public health threat in several countries. We have developed an in vivo model to investigate the host-ZIKV interaction in Drosophila We have found that a strain of ZIKV replicates in wild-type flies without reducing their survival ability. We have shown that ZIKV infection triggers RNA interference and that mutating Dicer-2 results in enhanced ZIKV load and increased susceptibility to ZIKV infection. Using a flavivirus-specific Ab, we have found that ZIKV is localized in the gut and fat body cells of the infected wild-type flies and results in their perturbed homeostasis. In addition, Dicer-2 mutants display severely reduced insulin activity, which could contribute toward the increased mortality of these flies. Our work establishes the suitability of Drosophila as the model system to study host-ZIKV dynamics, which is expected to greatly advance our understanding of the molecular and physiological processes that determine the outcome of this disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Drosophila Proteins / immunology*
  • Drosophila melanogaster / immunology
  • Drosophila melanogaster / virology
  • Homeostasis / immunology
  • Host-Pathogen Interactions / immunology*
  • RNA Helicases / immunology*
  • Ribonuclease III / immunology*
  • Zika Virus Infection / immunology*

Substances

  • Drosophila Proteins
  • DCR-2 protein, Drosophila
  • Ribonuclease III
  • RNA Helicases