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

Abstract

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 BoLA-DRB3 MHCII molecule. We performed an association study using sequencing-based typed BOLA-DRB3 alleles from over 800 Holstein and Holstein × Jersey cows considering LI in vivo and accounting for filial relationships. The DBR3*0902 allele was associated with a low level of infection (LLI) (<1% of circulating infected B-cells), whereas the DRB3*1001 and DRB3*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-DRB3 alleles were associated with LI. DRB3*0902 had unique haplotypes for each of the pockets: Ser -Glu -Arg -Glu (pocket 4), Ser -Ser (pocket 6), Glu -Trp -Arg (pocket 7) and Asn -Asp (pocket 9), and all of them were significantly associated with LLI. Conversely, Lys -Arg -Ala -Ala and Ser -Arg -Ala -Ala , corresponding to the DRB3*1001 and *1201 alleles respectively, were associated with HLI. We showed that the specific amino acid pattern in the DRB3*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-DRB3 alleles associated with a HLI, which is compatible with a highly contagious profile.

Early events following bovine leukaemia virus infection in calves with different alleles of the major histocompatibility complex DRB3 gene

“…The HPL phenotype has been associated with the BoLA-DRB3*1501 allele, while the LPL phenotype has been associated with the BoLA DRB3*0902 and *1701 alleles [19]. The association of proviral load with the BoLA-DRB3 polymorphism in BLV-infected cattle has been subsequently confirmed by others and extended to other bovine breeds [20][21][22][23].…”

Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations

“…A potential limitation of such approach is that the MHC-DR PBR positions used have been documented by X-ray crystallography just in humans and mice. Nevertheless, several of these positions have been associated with vaccine responses and susceptibility or resistance to infectious diseases (Garcia-Briones et al, 2000;Baxter et al, 2009;Rastislav and Mangesh, 2012;Carignano et al, 2017) and thus analysis based on these positions is reasonable.…”

“…Ascertaining cattle's BoLA-DRB3 allele frequency distribution in different regions worldwide has been used for executing infectious disease control programmes (Maillard et al, 2003) and can be applied to developing vaccines having a wider range of protection (Patarroyo et al, 2011). Different BoLA-DRB3 alleles have been associated with variations in susceptibility to infectious diseases (Dietz et al, 1997;Acosta-Rodriguez et al, 2005;Martinez et al, 2006;Nascimento et al, 2006;Kulberg et al, 2007;Juliarena et al, 2008;Nikbakht et al, 2016;Carignano et al, 2017), vaccine responses (Garcia-Briones et al, 2000;Rupp et al, 2007;Baxter et al, 2009;Gowane et al, 2013) and production traits (Sharif et al, 1999). BoLA-DRB3 genetic diversity has been characterized in both widespread and autochthonous creole cattle breeds (Takeshima et al, 2001;Takeshima et al, 2002;Takeshima et al, 2003;Baxter et al, 2008;Wang et al, 2008;Giovambattista et al, 2013;Takeshima et al, 2014;Takeshima et al, 2015a).…”

Genetic Diversity of Bovine Major Histocompatibility Complex Class II DRB3 locus in cattle breeds from Asia compared to those from Africa and America

“…BoLA-DRB3.2 which is the second exon of the third DRB bovine gene is responsible for the β1 domain of the only widely expressed DRB gene in cattle. There is an increasing effort to characterize bovine MHC allele frequencies by breed and location because of the role of BoLA-DRB3 allele in resistance and/or susceptibility to infectious diseases and immunology 6 , 7 , 8 .…”