Pathogenesis of Two Western Mediterranean West Nile Virus Lineage 1 Isolates in Experimentally Infected Red-Legged Partridges (Alectoris rufa).

Virginia Gamino,Miguel Ángel Jiménez-Clavero,Elisa Pérez-Ramírez,Elena Sotelo,Ana Valeria Gutiérrez-Guzmán,Francisco Llorente,Ursula Höfle

doi:10.3390/pathogens10060748

Abstract

West Nile virus (WNV) is the most widespread flavivirus in the world with a wide vertebrate host range. Its geographic expansion and activity continue to increase with important human and equine outbreaks and local bird mortality. In a previous experiment, we demonstrated the susceptibility of 7-week-old red-legged partridges (Alectoris rufa) to Mediterranean WNV isolates Morocco/2003 and Spain/2007, which varied in virulence for this gallinaceous species. Here we study the pathogenesis of the infection with these two strains to explain the different course of infection and mortality. Day six post-inoculation was critical in the course of infection, with the highest viral load in tissues, the most widespread virus antigen, and more severe lesions. The most affected organs were the heart, liver, and spleen. Comparing infections with Morocco/2003 and Spain/2007, differences were observed in the viral load, virus antigen distribution, and lesion nature and severity. A more acute and marked inflammatory reaction (characterized by participation of microglia and CD3+ T cells) as well as neuronal necrosis in the brain were observed in partridges infected with Morocco/2003 as compared to those infected with Spain/2007. This suggests a higher neurovirulence of Morocco/2003, probably related to one or more specific molecular determinants of virulence different from Spain/2007.

Highlights

West Nile virus (WNV) is an arthropod-borne flavivirus whose natural cycle involves bird hosts and mosquito vectors, with horses and humans as accidental or dead-end hosts [1]
In an experimental study we demonstrated that the red-legged partridge (Alectoris rufa), a Mediterranean endemic gallinaceous bird species [19], is susceptible to the infection with two lineage 1 Western Mediterranean WNV strains, Morocco/2003 [20] and
We studied differences in the pathogenesis after experimental infection of red-legged partridges with two different Mediterranean lineage 1 (L1) WNV isolates, Morocco/2003 and Spain/2007, to elucidate the cause of the different infection course and mortality observed during the experiment and described in a previous work [17]

Summary

Introduction

West Nile virus (WNV) is an arthropod-borne flavivirus whose natural cycle involves bird hosts and mosquito vectors, with horses and humans as accidental or dead-end hosts [1]. It is considered one of the most widely distributed arboviruses in the world, causing numerous human, equine, and bird outbreaks and mortalities, both in the Old and New World [2,3]. In the Mediterranean basin, WNV activity is continuously increasing, and has been associated with several outbreaks affecting mainly humans and horses [4,5]. Under laboratory conditions in experimental infections, at least some Mediterranean L1 WNV strains have proven to be pathogenic for European wild bird species [14,15,16,17,18]. 4.0/).

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