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.

Highlights

  • The recent Zika virus (ZIKV) outbreak has reminded us that the emergence of new viruses depends on multiple factors and is extremely difficult to predict

  • Usutu virus (USUV) is an African mosquito-borne virus closely related to West Nile virus and belongs to the Japanese encephalitis virus serogroup in the Flavivirus genus

  • The goal of our work was to study the ability of USUV to infect neuronal cells and to characterize the effects of USUV infection in these cells

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Summary

Introduction

The recent Zika virus (ZIKV) outbreak has reminded us that the emergence of new viruses depends on multiple factors and is extremely difficult to predict. Usutu virus (USUV) has recently focused attention. USUV is an African mosquito-borne virus closely related to West Nile virus (WNV) that belongs to the Japanese encephalitis virus (JEV) serogroup in the Flavivirus genus (Flaviviridae family) [1]. USUV was discovered in 1959 from a mosquito of the Culex neavei species in South Africa and isolated by intracerebral inoculation of newborn mice [2]. USUV natural life cycle is similar to WNV: it involves birds as reservoirs and ornithophilic mosquitoes as vectors like the common Culex pipiens. USUV-infected mosquitoes were recently detected in several European countries [6,7]. Mammals including horses or wild boars, were described as accidental or dead-end hosts [8,9,10]

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