Abstract
Lineage 2 West Nile virus (WNV) strains were reported for the first time in Europe in 2004. Despite an almost silent circulation around their entry point in Hungary, an upsurge of pathogenicity occurred in 2010 as 262 people suffered from neuroinvasive disease in Greece. This increase in virulence was imputed to the emergence of a His249Pro mutation in the viral NS3 helicase, as previously evidenced in American crows experimentally infected with the prototype lineage 1 North-American WNV strain. However, since 2003, WNV strains bearing the NS3Pro genotype are regularly isolated in Western-Mediterranean countries without being correlated to any virulent outbreak in vertebrates. We thus sought to evaluate the weight of the NS3249Pro genotype as a virulence marker of WNV in an in vivo avian model of WNV infection. We therefore characterized three genetically-related Eastern-Europe lineage 2 WNV strains in day-old specific pathogen-free (SPF) chickens: Hun2004 and Aus2008 which are both characterized by a NS3249His genotype, and Gr2011 which is characterized by a NS3249Pro genotype. Unlike Hun2004 and Aus2008, Gr2011 was weakly virulent in SPF chicks as Gr2011-induced viremia was lower and waned quicklier than in the Hun2004 and Aus2008 groups. Overall, this study showed that the presence of a proline residue at position 249 of the viral NS3 helicase is neither sufficient nor necessary to confer pathogenicity to any given lineage 2 WNV strain in birds.
Highlights
West Nile virus (WNV) is a mosquito-borne, positive sense, single-stranded RNA virus that belongs to the Flavivirus genus (Flaviviridae family), and that falls within the Japanese encephalitis virus antigenic complex [1]
The dose of 103 tissue culture infectious dose 50 (TCID50) was chosen because it is close to the dose usually inoculated by C. pipiens mosquitoes during natural infections (i.e. 104.3 PFU, [39]), and because we showed in a previous work [37] that this dose allows a significant discrimination between different pathotypes of lineage 1 West Nile virus strains in the specific pathogen-free (SPF) chicken model, based on mortality rates
We have compared in this study the pathogenic profile of related lineage 2 WNV strains bearing either a NS3249Pro or a NS3249His genotype, while previous studies dealing with NS3249 polymorphism usually compared NS3249Pro genotype with NS3249Thr genotype [25, 28, 30, 40]
Summary
West Nile virus (WNV) is a mosquito-borne, positive sense, single-stranded RNA virus that belongs to the Flavivirus genus (Flaviviridae family), and that falls within the Japanese encephalitis virus antigenic complex [1]. The same year, the first human outbreak of neuroinvasive disease due to a lineage 2 WNV was reported in Romania [14] This outbreak was caused by a strain that was highly similar to a Volgograd lineage 2 strain involved in an outbreak in Russia in the Volga Delta area in 2007, but is unrelated to the GreekHungarian lineage 2. In 2011, a lineage 2 WNV strain related to the Hungarian-Greek strains was reported for the first time in a dead Eurasian collared dove (Streptopelia decaocto) and in Culex pipiens mosquitoes in North-Eastern Italy and in at least two febrile patients from Central Italy and Sardinia [16,17,18] and caused at least 7 human cases of WNND in 2013 in the Po river area [19,20,21]. Four lineage 2 isolates closely related to the Austrian, Italian and Serbian strains reported in 2008, 2011 and 2012 respectively, were detected in mosquitoes in the Czech Republic during 2013 [24]
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