Project Number: 5430-32000-006-00
Project Type: Appropriated

Start Date: Oct 01, 2012
End Date: Feb 28, 2017

Objective:
Objective 1: Determine the molecular and biological characteristics of emergent, re-emergent, and previously uncharacterized bluetongue virus isolates. Sub-objective A. Develop means to detect and characterize emergent viruses. Objective 2: Assess the risk of North American ruminants to emergent, re-emergent, and previously uncharacterized bluetongue virus isolates. Sub-objective A. Develop BTV “vector-transmitted” infectious models in target ruminant species to facilitate disease pathogenesis, disease transmission and vaccine efficacy studies. Sub-objective B. Identify mammalian host innate and adaptive responses to insect transmitted BTV.

Approach:
Bluetongue virus (BTV) is transmitted by Culicoides midges to wild and domestic ruminants, especially sheep, and results in significant economic losses from decreased animal production and non-tariff trade restrictions on animals and animal products. Of the 26 BTV serotypes, only five are considered domestic to the U.S., although 10 exotic types have been introduced since 1999. There is an ever-increasing need for veterinary diagnostic laboratories to reliably detect multiple serotypes in submitted samples. We propose to develop rapid, sensitive, specific diagnostic assays to detect and differentiate multiple serotypes of BTV and anti-BTV antibodies in cattle and sheep from a single blood or serum sample. There are major gaps in understanding underlying mechanisms of disease and transmission of different serotypes, not only at the level of virus-vector-host interaction, but also at the herd and animal population levels. One major issue is our inability to experimentally demonstrate clinical bluetongue disease in sheep and cattle, critical for understanding pathogenesis and vaccine development and evaluation. Traditional injection infection models completely remove the insect from the equation and expose cell types and elicit immune responses atypical of natural infections. These dissimilarities may play a significant role in the clinical disease differences seen in natural versus laboratory infections. We will evaluate the role of virus delivery routes (subcutaneous versus intradermal) and the role insect salivary proteins play in virus infection, pathogenesis and immune responses to BTV. The long term goal is to develop a robust BTV infection and disease animal model; a critical need for bluetongue infection, pathogenesis and vaccine research.