Céline Bahuon

Differential Virulence and Pathogenesis of West Nile Viruses

West Nile virus (WNV) is a neurotropic flavivirus that cycles between mosquitoes and birds but that can also infect humans, horses, and other vertebrate animals. In most humans, WNV infection remains subclinical. However, 20%–40% of those infected may develop WNV disease, with symptoms ranging from fever to meningoencephalitis. A large variety of WNV strains have been described worldwide. Based on their genetic differences, they have been classified into eight lineages; the pathogenic strains belong to lineages 1 and 2. Ten years ago, Beasley et al. (2002) found that dramatic differences exist in the virulence and neuroinvasion properties of lineage 1 and lineage 2 WNV strains. Further insights on how WNV interacts with its hosts have recently been gained; the virus acts either at the periphery or on the central nervous system (CNS), and these observed differences could help explain the differential virulence and neurovirulence of WNV strains. This review aims to summarize the current state of knowledge on factors that trigger WNV dissemination and CNS invasion as well as on the inflammatory response and CNS damage induced by WNV. Moreover, we will discuss how WNV strains differentially interact with the innate immune system and CNS cells, thus influencing WNV pathogenesis.

Dual Emergence of Usutu Virus in Common Blackbirds, Eastern France, 2015.

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IS-98-ST1 West Nile Virus Derived from an Infectious cDNA Clone Retains Neuroinvasiveness and Neurovirulence Properties of the Original Virus

Infectious clones of West Nile virus (WNV) have previously been generated and used to decipher the role of viral proteins in WNV virulence. The majority of molecular clones obtained to date have been derived from North American, Australian, or African isolates. Here, we describe the construction of an infectious cDNA clone of a Mediterranean WNV strain, IS-98-ST1. We characterized the biological properties of the recovered recombinant virus in cell culture and in mice. The growth kinetics of recombinant and parental WNV were similar in Vero cells. Moreover, the phenotype of recombinant and parental WNV was indistinguishable as regards viremia, viral load in the brain, and mortality in susceptible and resistant mice. Finally, the pathobiology of the infectious clone was examined in embryonated chicken eggs. The capacity of different WNV strains to replicate in embryonated chicken eggs closely paralleled their ability to replicate in mice, suggesting that inoculation of embryonated chicken eggs could provide a practical in vivo model for the study of WNV pathogenesis. In conclusion, the IS-98-ST1 infectious clone will allow assessment of the impact of selected mutations and novel genomic changes appearing in emerging European strains pathogenicity and endemic or epidemic potential. This will be invaluable in the context of an increasing number of outbreaks and enhanced severity of infections in the Mediterranean basin and Eastern Europe.

La fièvre catarrhale ovine (ou «bluetongue») dans le nord de l'Europe

La fievre catarrhale ovine, aussi appelee « bluetongue », est une arbovirose transmise par un moucheron hematophage du genre Culicoides. Elle se manifeste cliniquement principalement chez les moutons et se traduit par une infection generalisee et grave. Depuis sa reapparition en Europe en 1998, cinq serotypes (1, 2, 4, 9 et 16) sur les 24 existants ont ete recenses dans de nombreux pays du pourtour mediterraneen. En France, seulement la region Corse a subi quatre epizooties impliquant les serotypes 2, 4 et 16. En 2006, de facon inattendue, la bluetongue (serotype 8) a emerge en Belgique, Allemagne, Pays bas, France et au Luxembourg. La symptomatologie associee a cette epizootie a de quoi surprendre, puisque les bovins presentent des signes cliniques de gravite variable, alors que classiquement, le virus de la bluetongue ne provoque que tres rarement des manifestations cliniques dans cette espece. Les caracteristiques de cette epizootie, les methodes de diagnostic et les moyens prophylactiques seront presentes dans cet article.