BOLA‐DRB3 gene polymorphisms influence bovine leukaemia virus infection levels in Holstein and Holstein × Jersey crossbreed dairy cattle

Summary Bovine leukemia virus ( BLV ) infections, causing persistent lymphocytosis and lethal lymphosarcoma in cattle, have reached high endemicity on dairy farms. We observed extensive inter‐individual variation in the level of infection ( LI ) by assessing differences in proviral load in peripheral blood. This phenotypic variation appears to be determined by host genetics variants, especially those located in the Bo LA ‐ DRB 3 MHCII molecule. We performed an association study using sequencing‐based typed BOLA ‐ DRB 3 alleles from over 800 Holstein and Holstein × Jersey cows considering LI in vivo and accounting for filial relationships. The DBR 3*0902 allele was associated with a low level of infection ( LLI ) (<1% of circulating infected B‐cells), whereas the DRB 3*1001 and DRB 3*1201 alleles were related to a high level of infection ( HLI ). We found evidence that 13 polymorphic positions located in the pockets of the peptide‐binding cleft of the BOLA ‐ DRB 3 alleles were associated with LI . DRB 3*0902 had unique haplotypes for each of the pockets: Ser 13 ‐Glu 70 ‐Arg 71 ‐Glu 74 (pocket 4), Ser 11 ‐Ser 30 (pocket 6), Glu 28 ‐Trp 61 ‐Arg 71 (pocket 7) and Asn 37 ‐Asp 57 (pocket 9), and all of them were significantly associated with LLI . Conversely, Lys 13 ‐Arg 70 ‐Ala 71 ‐Ala 74 and Ser 13 ‐Arg 70 ‐Ala 71 ‐Ala 74 , corresponding to the DRB 3*1001 and *1201 alleles respectively, were associated with HLI . We showed that the specific amino acid pattern in the DRB 3*0902 peptide‐binding cleft may be related to the set point of a very low proviral load level in adult cows. Moreover, we identified two BOLA ‐ DRB 3 alleles associated with a HLI , which is compatible with a highly contagious profile.