Host genetic mechanism of resistance and susceptibility to a bovine retroviral infection

Abstract

The bovine leukemia virus (BLV) has approximately 50% nucleotide sequence similarity to HTLV types I and II, and shares common regulatory mechanisms, but differs in host cell tropism, with B‐cells comprising the primary target of infection. We have shown that progression of BLV infection to persistent lymphocytosis (PL) is under the control of the bovine major histocompatibility complex, mapping closest to BoLA class II genes. We recently narrowed the association to exon 2 of the BoLA‐DRB3 gene. This exon was cloned from animals with BoLA haplotypes previously found to be associated with resistance and susceptibility to PL. Sequence analysis revealed the presence of the amino acids Glu‐Arg (ER) at putative antigen binding residues 70 and 71 only in BoLA haplotypes associated with resistance. This correlation was confirmed in a case‐control study using an allele‐specific polymerase chain reaction for the detection of the ER motif at residues 70‐71. Analysis of infection in peripheral blood leukocytes by a new single cell detection methodology revealed that BLV‐infected PL‐resistant animals have fewer infected peripheral cells than age‐matched susceptible cows. These results provide a molecular basis for Ir gene control of resistance and susceptibility to PL and suggest that the cellular immune response is important in preventing the in vivo spread of BLV infection.