THE IMMUNE-RESPONSE OF CATTLE, PERSISTENTLY INFECTED WITH NONCYTOPATHIC BVDV, AFTER SUPERINFECTION WITH ANTIGENICALLY SEMI-HOMOLOGOUS CYTOPATHIC BVDV

Cattle persistently infected (PI) with noncytopathic (ncp) bovine viru s diarrhea virus (BVDV) are at risk for developing fatal mucosal disea se (MD), which is considered to occur after superinfection with antige nically homologous cytopathic (cp) BVDV. In this study, we intranasall y inoculated four PI-animals, that were PI with 2 ncp BVDV strains wit h 10(5) TCID50 antigenically closely related cp BVDV. Two PI-animals w ere inoculated with 10(5) TCID50 ncp BVDV and one PI-animal with virus free cell culture medium. Two out of four PI-animals that were inocul ated with cp BVDV, developed MD and were euthanized at day 17 and at d ay 24 after infection. Postmortem, both animals showed typical lesions of MD and cp BVDV was isolated. The other two PI-animals that were in oculated with cp BVDV did not develop MD and were euthanized at day 51 . They showed ulcerations in the gastrointestinal tract, cp BVDV was i solated and neutralizing antibodies were detected. From the three PI-a nimals, that were inoculated with ncp BVDV or cell culture medium, cp BVDV was also isolated. Cross neutralization tests were performed and no antigenic differences could be detected between the cp strains isol ated from the PI-animals. Lymphocyte subsets of these PI-animals were determined by flow cytometric analysis. Before superinfection, the per centages of gamma delta subsets were much higher in the PI-animals tha t did not develop MD than in nonviremic control animals and in the PI- animals that died of MD. From this study we conclude that the presence of antigenically closely related cp BVDV in PI-animals does not neces sarily lead to the development of MD and that besides the antigenic re latedness between the persisting ncp BVDV and cp BVDV other factors, f or instance the number of circulating gamma delta cells, might determi ne whether or not PI-animals develop MD. (C) 1998 Elsevier Science B.V .