Single amino acid differences are sufficient for CD4(+) T-cell recognitionof a heterologous virus by cattle persistently infected with bovine viral diarrhea virus

Cattle that are persistently infected (PI) with one strain of bovine viral diarrhea virus (BVDV) can resolve infection with a second, antigenically he terologous strain but not the homologous strain. Since CD4(+) T cells are t hought to be critical for the resolution of acute BVDV infection (Howard et al., 1992, Vet Immunol. Immunopathol. 32, 303-314), we have examined the r ecognition of a heterologous virus (NADL) by CD4(+) T cells from Pe515-PI a nimals. The immune response of non-PI control cattle challenged with NADL o r Pe515ncp was strain cross-reactive, whereas Pe515-PI animals responded to NADL only. The immune repertoire of both groups included NS3, which differ s by approximately 1% (9/683) amino acids between these two viruses. Lympho proliferative responses to proteins and synthetic peptides corresponding to three nonconservative differences in NS3 demonstrated that CD4(+) T cells from non-PI control animals responded well to proteins but poorly to the pe ptides from both viruses. In contrast, PI animals were responsive to hetero logous proteins and peptides but nonresponsive to the homologous equivalent s. A single amino acid difference between the two sequences was sufficient to allow responsiveness. (C) 2000 Academic Press.