Shipping fever – pathogenesis and vaccine development

Cells expression BHV-1 VP8 and US3

Project Team: Sylvia van den HurkPhilip Griebel, Marlene Snider

Bovine herpesvirus 1 (BHV-1) and bovine viral diarrhea virus (BVDV) are the major viral pathogens that cause shipping fever.

BHV-1 causes respiratory and genital tract infections, but can also cause abortions in pregnant cows. Clinical symptoms include nasal lesions and discharge, cough, increased respiratory rate, fever, anorexia and weight loss. BHV-1 suppresses the immune response, which predisposes calves to fatal secondary bacterial infections. Subsequent to primary infection, BHV-1 remains in the host in a latent state. Reactivation occurs due to stress such as inclement weather, transportation or overcrowding of animals.

Our goal is to perform a functional characterization of the impact of major tegument proteins of BHV-1 on the intrinsic response to infection. Infection of bovine cells or calves with BHV-1 leads to a robust interferon (IFN) response. This suggests that multiple and robust mechanisms/proteins are needed early during BHV-1 infection to counteract these responses. We have found one of the major components of the virion, VP8, to down-regulate the IFN response. A mutant virus lacking VP8 is impaired in growth in vitro and non-virulent in vivo. We are further characterizing the function of this and additional tegument proteins, as well as developing attenuated mutant viruses.

BVDV causes fever, increased respiratory rate, diarrhea, and low white blood cell (WBC) counts. Certain strains cause persistent infections in fetuses of cows infected during early stages of gestation. Although these calves may die, survivors act as viral reservoirs and may have birth defects or stunted growth.

Our goal is to develop an effective subunit vaccine against BVDV based on one of the protective antigens, the E2 protein, formulated with a new combination adjuvant.