Deleterious effect of Usutu virus on human neural cells

PLoS Negl Trop Dis. 2017 Sep 5;11(9):e0005913. doi: 10.1371/journal.pntd.0005913. eCollection 2017 Sep.

Abstract

In the last decade, the number of emerging Flaviviruses described worldwide has increased considerably. Among them Zika virus (ZIKV) and Usutu virus (USUV) are African mosquito-borne viruses that recently emerged. Recently, ZIKV has been intensely studied due to major outbreaks associated with neonatal death and birth defects, as well as neurological symptoms. USUV pathogenesis remains largely unexplored, despite significant human and veterinary associated disorders. Circulation of USUV in Africa was documented more than 50 years ago, and it emerged in Europe two decades ago, causing massive bird mortality. More recently, USUV has been described to be associated with neurological disorders in humans such as encephalitis and meningoencephalitis, highlighting USUV as a potential health threat. The aim of this study was to evaluate the ability of USUV to infect neuronal cells. Our results indicate that USUV efficiently infects neurons, astrocytes, microglia and IPSc-derived human neuronal stem cells. When compared to ZIKV, USUV led to a higher infection rate, viral production, as well as stronger cell death and anti-viral response. Our results highlight the need to better characterize the physiopathology related to USUV infection in order to anticipate the potential threat of USUV emergence.

MeSH terms

  • Animals
  • Astrocytes / physiology
  • Astrocytes / virology*
  • Brain / virology
  • Cells, Cultured
  • Encephalitis Viruses, Japanese / growth & development
  • Encephalitis Viruses, Japanese / physiology*
  • Mice
  • Neural Stem Cells / physiology
  • Neural Stem Cells / virology*
  • Neuroglia / physiology
  • Neuroglia / virology*
  • Neurons / physiology
  • Neurons / virology*
  • Organ Culture Techniques
  • Viral Tropism*
  • Zika Virus / growth & development
  • Zika Virus / physiology

Grant support

This work was funded by La Région Languedoc-Roussillon (http://www.midipyrenees.fr/-Accueil-Enseignement-superieur-Recherche-) and REACting (https://www.inserm.fr/zoom/reacting-une-approche-multidisciplinaire-pour-relever-le-defi-des-crises-epidemiques). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.