Cross-infection studies of normal calves infected with homologous pairs of non-cytopathic and cytopathic bovine viral diarrhoea virus (BVDV) showed significant differences in both humoral and cell-mediated immune responses against either biotype over a period of 5 months. Serological assays after primary intranasal inoculation showed striking significant (P < 0.05) differences between biotypes. Neutralizing titres were detected earlier and were much higher with the non-cytopathic strain than with the homologous cytopathic strain. Significant biotype-specific differences were also observed in the lymphocyte proliferative responses of cattle following in vitro stimulation by non-cytopathic/cytopathic BVDV and the non-structural p80 protein (NS3). The secondary immune response seems to be largely influenced by the biotype used for the primary inoculation and only to a lesser extent by the biotype inoculated for the second time after an interval of 91 days. Animals exposed twice to the cytopathic biotype, which exhibited the lowest antibody titres, showed evidence of BVDV-specific cell-mediated immunity as measured by lympho-proliferation against BVDV. In contrast, the antibody response in the subgroup of animals inoculated twice with homologous non-cytopathic virus was inversely correlated with the proliferative responses. These differences in the immune response were not readily apparent for the two other remaining subgroups which had received cytopathic or non-cytopathic biotypes alone following the second inoculation with non-cytopathic or cytopathic viruses, respectively. Taken together, these data suggest that the differences in immune responses against cytopathic or non-cytopathic strains may be due to a Th1/Th2-like regulatory mechanism.


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