In Vitro and In Vivo Models to Study the Zoonotic Mosquito-Borne Usutu Virus

Abstract

Usutu virus (USUV), a mosquito-borne zoonotic flavivirus discovered in South Africa in 1959, has spread to many European countries over the last 20 years. The virus is currently a major concern for animal health due to its expanding host range and the growing number of avian mass mortality events. Although human infections with USUV are often asymptomatic, they are occasionally accompanied by neurological complications reminiscent of those due to West Nile virus (another flavivirus closely related to USUV). Whilst USUV actually appears less threatening than some other emergent arboviruses, the lessons learned from Chikungunya, Dengue, and Zika viruses during the past few years should not be ignored. Further, it would not be surprising if, with time, USUV disperses further eastwards towards Asia and possibly westwards to the Americas, which may result in more pathogenic USUV strains to humans and/or animals. These observations, inviting the scientific community to be more vigilant about the spread and genetic evolution of USUV, have prompted the use of experimental systems to understand USUV pathogenesis and to boost the development of vaccines and antivirals. This review is the first to provide comprehensive coverage of existing in vitro and in vivo models for USUV infection and to discuss their contribution in advancing data concerning this neurotropic virus. We believe that this paper is a helpful tool for scientists to identify gaps in the knowledge about USUV and to design their future experiments to study the virus.

Analysis of avian Usutu virus infections in Germany from 2011 to 2018 with focus on dsRNA detection to demonstrate viral infections

“…Organs that were found to be antigen positive by immunohistochemistry contained cultivable infectious virus when inoculated in permissive cell lines. Similar findings were reported in several studies 56 , 59 , 60 . However, in most studies, virus isolation was not possible in all animals examined due to poor state of preservation 9 , 23 , 56 , 60 , 61 .…”

Pathology and Pathogenesis of Eurasian Blackbirds (Turdus merula) Naturally Infected with Usutu Virus

“…The Usutu virus causes mass mortality in avian species and leads to asymptomatic to mild or neuroinvasive forms of disease in humans [ 1 , 3 ]. In birds naturally infected with USUV, knowledge about pathology and cell and tissue tropism is still fragmentary.…”

“…Usutu virus (USUV) is a zoonotic arbovirus (genus Flavivirus, family Flaviviridae) infecting birds and humans [ 1 , 2 , 3 , 4 ]. In birds, it is reported as a cause of mass mortality, mainly affecting passerines and birds of prey.…”

Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication

“…The infection is transmitted through the bites of infected mosquitoes, primarily by the genus Culex . From a research point of view, USUV is an attractive pathogen as it generally requires lower biosafety containment levels than other genetically related pathogens which makes it suitable as a model to study flavivirus biology and infection [ 11 ]. In recent years, it has also become an increasingly interesting pathogen from a human health perspective, with an increase in the number of cases associated with neurological disease [ 12 , 13 , 14 ].…”