The pathogenesis and immunology of bluetongue virus infection of ruminants

Abstract

Bluetongue (BLU) virus is transmitted from infected to susceptible ruminants by hematophagous vector midges (Culicoides species). Cattle are important reservoir hosts of the virus because infection typically is asymptomatic and characterized by prolonged cell associated viremia, and because at least some species of insect vector preferentially feed on cattle. Interaction of BLU virus with the cell membrane of erythrocytes in infected cattle likely facilitates both prolonged viremia as well as infection of the insect vector. BLU disease is most common in sheep and some wildlife species. A variety of host, agent and environmental factors clearly can influence expression of disease in these species. The pathogenesis of BLU virus infection of cattle and sheep is remarkably similar, thus the basis for expression of disease in sheep but not cattle remains to be firmly established. Some difference in susceptibility of endothelial cells to infection in the two species is one potential explanation. Ruminants develop a variety of antiviral responses after BLU virus infection. Antibodies to outer capsid protein VP2 are responsible for virus neutralization, and confer resistance to reinfection with the homologous serotype of BLU virus. Antibodies to epitopes on proteins which are common to all viruses of the BLU serogroup form the basis of current diagnostic serologic tests. Cell mediated responses have been incompletely characterized, in part because BLU virus replicates within dividing lymphocytes and virus-mediated cytolysis inhibits in vitro blastogenesis. Immunological competence of ruminants to BLU virus arises prior to midgestation, and suggestions that persistent immune tolerant BLU virus infection occurs after in utero exposure of cattle have not been substantiated and are not consistent with recent findings.