Shipping fever – pathogenesis and vaccine development
BHV-1 primarily causes respiratory tract and genital tract infections, but can also infect the fetus and cause abortions in pregnant cows. Clinical symptoms include nasal lesions and discharge, cough, increased respiratory rate, fever, anorexia and weight loss. Calves over three months of age generally recover within 10-12 days. However, BHV-1 may also spread to the eyes where it causes conjunctivitis, the brain leading to encephalitis, or the lower respiratory tract. BHV-1 suppresses the immune response at several levels, which predisposes calves to fatal secondary bacterial infections, for example Mannheimia. haemolytica. Subsequent to primary infection, BHV-1 remains in the host in a latent state in the trigeminal ganglia. Reactivation occurs due to stress such as inclement weather, transportation or overcrowding of animals.
The goal of this project is to perform a functional characterization of the impact of major proteins of BHV-1 on the intrinsic response to infection. Infection of bovine cells or calves with BHV-1 leads to a robust IFN response. This suggests that multiple and robust mechanisms/proteins are needed early during BHV-1 infection to counteract these responses. We have identified one of the major components of the virion, VP8, as an important virulence factor in BHV-1. A deletion lacking VP8 is impaired in growth in vitro and non-virulent in vivo. We are further characterizing the function of this protein, and generating additional mutants by deleting parts and/or phosphorylation sites of VP8.
- Determine how VP8 down-modulates cellular anti-viral resistance
- Identify additional virulence factors of BHV-1
- Develop attenuated BHV-1 mutant virus