Abstract

Bluetongue (BT) is a noncontagious, insect-transmitted disease of ruminants caused by the bluetongue virus (BTV). A laboratory animal model would greatly facilitate the studies of pathogenesis, immune response and vaccination against BTV. Herein, we show that adult mice deficient in type I IFN receptor (IFNAR(−/−)) are highly susceptible to BTV-4 and BTV-8 infection when the virus is administered intravenously. Disease was characterized by ocular discharges and apathy, starting at 48 hours post-infection and quickly leading to animal death within 60 hours of inoculation. Infectious virus was recovered from the spleen, lung, thymus, and lymph nodes indicating a systemic infection. In addition, a lymphoid depletion in spleen, and severe pneumonia were observed in the infected mice. Furthermore, IFNAR(−/−) adult mice immunized with a BTV-4 inactivated vaccine showed the induction of neutralizing antibodies against BTV-4 and complete protection against challenge with a lethal dose of this virus. The data indicate that this mouse model may facilitate the study of BTV pathogenesis, and the development of new effective vaccines for BTV.

Highlights

  • Bluetongue (BT) is an infectious noncontagious viral disease of ruminants caused by the bluetongue virus (BTV)

  • Since blood is the natural route of BTV infection in ruminants, adult C57BL/6 and IFNAR(2/2) mice were infected intravenously (i.v.) with 106 PFUs of BTV-4

  • IFNAR(2/2) mice were susceptible to BTV-4 infection (Fig. 1A), showing disease symptoms characterized by ocular discharges and apathy starting at 48 h.p.i

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Summary

Introduction

Bluetongue (BT) is an infectious noncontagious viral disease of ruminants caused by the bluetongue virus (BTV). The virus, consisting of 24 different serotypes, is transmitted to its vertebrate host by a few species of biting midges of the Culicoides genus (Diptera: Ceratopogonidae) [1]. BT is a reportable disease of considerable socioeconomic concern and of major importance in the international trade of animals and animal products. Since August 2006, BTV-8 has caused severe epizootic outbreakes in northern Europe [5]. The emergence of BT in parts of Europe never before affected was attributed mainly to climate change and linked to the Northern expansion of the major Old World vector Culicoides imicola. There is evidence for the involvement of other novel indigenous European vector species of Culicoides (C. obsoletus and C. pulicaris ) [6]

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