Infectious blood or culture-grown virus: a comparison of bluetongue virus challenge models.

The World Organisation for Animal Health (OIE) currently recommends using infectious ruminant blood as challenge inoculum in bluetongue virus (BTV) vaccination and challenge experiments. The use of virus grown in cultured cells is discouraged because culture passages can lead to changes in virus phenotype, including reduced replication efficiency and virulence in the host, while the OIE considers clinical disease in control animals indispensable evidence of successful infection. In the present study, two groups of five sheep were inoculated with either infectious calf blood lysate or culture-grown bluetongue virus of serotype 8 (BTV-8) (2 × 10(4)TCID(50) and 5 × 10(5)TCID(50), respectively). No pronounced difference in the induction and progression of viraemia as determined by real-time RT-PCR, which is the most objective parameter in the evaluation of vaccine efficacy, was observed. In a second experiment, the virulence of both inocula was confirmed by fatal infection of interferon receptor-deficient mice. The recent availability of highly sensitive molecular methods for the detection of BTV can finally shift the focus away from clinical disease. For the sake of objective and repeatable BTV challenge experiments, the OIE should reconsider its policy on culture-grown virus.