MOLECULAR BIOLOGY AND PATHOGENESIS OF ARBOVIRUSES
Project Number: 5410-32000-016-00
Start Date: Feb 01, 2007
End Date: Dec 10, 2008
Arthropod-borne viruses (arboviruses) are important pathogens of livestock and have a significant impact on the US livestock industry. These viruses have a complex life cycle and often infect not only animals but also humans. The rapid spread of West Nile virus shows the danger from invasive arboviruses. We will characterize viral and host proteins important in the infections cycle. The pathogenesis of epizootic hemorrhagic disease virus (EHDV) infection in cattle is not well understood. We will determine if the difference in EHDV virulence between cattle and deer is related to endothelial cell tropism. We will also examine the effect on the fetus of EHDV infection of pregnant cattle. Effective control of arbovirus infections requires sensitive and specific diagnostics and efficacious vaccines. We will develop tests for the detection of viral antibody, viral particles, viral antigens, and viral nucleic acids. Epizootics caused by West Nile virus and vesicular stomatitis virus result in significant morbidity and mortality in the equine and bovine industries. At present there is no vaccine for these viruses. We will develop and evaluate vaccines for both of these viruses. We will (1) elucidate mechanisms of infections with arboviruses and pathogenesis with epizootic hemorrhagic disease virus; (2) clarify the role of Culicoides saliva in arbovirus infections; and (3) develop additional diagnostic tests for arboviruses and more efficacious preventative measure for arboviruses.
Receptors for arboviruses will be characterized. Mechanisms of virus neutralization in vertebrate and invertebrate cells will be determined. The role of the BTV hemagglutinin in transmission of virus from infected mammalian hosts to insect vectors will be studied. The effect of EHDV infection on the bovine fetus will be investigated. EHDV replication in cattle and deer cells will be studied. The effects of insect saliva proteins on VSV replication in mammalian cells will be examined. Insect genes coding for proteins that affect virus replication in the insect will be identified. Specific diagnostic tests for BTV, EHDV, VSV and WNV will be developed and tested. The potential efficacy of a mucosal vaccine for protection against VSV infections will be tested. Research will be carried out to show that intracellular antibodies can protect against BTV infection.