Association of BLV infection profiles with alleles of the BoLA‐DRB3.2 gene

Abstract

Bovine leukaemia virus (BLV) causes lymphosarcoma and persistent lymphocytosis (PL). Some MHC class II gene polymorphisms have been associated with resistance and susceptibility to the development of lymphosarcoma and PL, as well as with a reduced number of circulating BLV-infected lymphocytes. Previously, 230 BLV-infected Holstein cattle were classified into two infection profiles characterized by low and high proviral loads (LPL and HPL respectively). Here, the influence of the polymorphism at the BoLA-DRB3.2* gene of these animals was examined. After genotyping, the association between the BoLA-DRB3.2* alleles and the BLV infection profile was determined as the odds ratio (OR). Two subtypes of allele *11 were identified (ISAG*0901 and *0902). Allele ISAG*0902 showed a stronger association with the LPL profile (OR = 8.24; P < 0.0001) than allele *11 itself (OR = 5.82; P < 0.0001). Allele ISAG*1701 (*12) also showed significant association with the LPL profile (OR = 3.46; P < 0.0055). Only one allele, ISAG*1501 or 03 (*16), showed significant association with HPL (OR = 0.36; P < 0.0005). The DRB3.2* alleles were assigned to three categories: resistant (R), susceptible (S) and neutral (N). Based on their DRB3 genotypes, cattle were classified as homozygous or heterozygous. The RR and RN genotypes were associated with the LPL profile, while the SS and NS genotypes were associated with the HPL profile. The RS genotype could not be associated with any particular profile. Our results show that allele ISAG*0902 appears to be the best BLV resistance marker in Holstein cattle.

A novel association of BoLA DRB3 alleles in BLV infected cattle with different proviral loads

“…In the present investigation we found a significant number of animals carrying this allele in our herd, compared to the population of Holstein in Argentina (TAKESHIMA et al, 2015); however, no association could be established between allele BoLA DRB3.2*1101 and BLV PVL. In the literature BoLA DRB3.2*0902 (or *11 determined by PCR-RFLP) allele was most strongly associated with PL resistance or LPVL profile in Holstein cattle (XU et al, 1993;ZANOTTI et al, 1996;MIRSKY et al, 1998;JULIARENA et al, 2008;PANEI et al, 2009;MIYASAKA et al, 2013). In the present investigation we did not find this association, which could be due to a lower frequency of presentation of *0902 allele in this herd in comparison with the Argentinean Holstein populations (4.21% vs 6.4%, respectively) (TAKESHIMA et al, 2015).…”

“…Related to the infection with BLV in Holstein breed, several studies have shown that the susceptibility to PL was associated with the presence of BoLA DRB3*0101, *1501 or 03, *1101 or 02, and *1201 (XU et al, 1993;ZANOTTI et al, 1996;MIRSKY et al, 1998;JULIARENA et al, 2008;PANEI et al, 2009;NIKBAKHT BRUJENI et al, 2016). In the present study, BoLA DRB3*1201 was the most significantly associated with HPVL (p = 0.0111), and this might be due to the fact that its frequency in the investigated population was about one third higher than in other Argentinean Holstein populations (11.21% vs 7.3%, respectively) (TAKESHIMA et al, 2015).…”

“…In this investigation we also found a strong association between HPVL and the presence of BoLA DRB3*1501 (p = 0.0230). These two alleles are the most frequently associated with susceptibility to PL or HPVL in BLV-infected animals from different cattle breeds (XU et al, 1993;SULIMOVA et al, 1995;ZANOTTI et al, 1996;UDINA et al, 2003;JULIARENA et al, 2008). BoLA DRB3*1001 had the highest frequency in the investigated herd, and in the literature it was referred as a susceptible (XU et al, 1993;UDINA et al, 2003) or a neutral allele (XU et al, 1993) for PL development.…”

“…Genetic selection for BoLA DRB3.2*0902 allele has been proposed to breed cattle that are resistant to HPVL development (JULIARENA et al, 2016 (JULIARENA et al, 2008). It must be considered that expression of BoLA DRB3 might be influenced by polymorphisms in other surrounding genes.…”

“…Some alleles were associated with resistance to PL or to BLV-induced lymphosarcoma, or the capability of controlling the number of BLV-infected cells, while other alleles were associated with susceptibility to PL (XU et al, 1993;ZANOTTI et al, 1996;MIRSKY et al, 1998;PANEI et al, 2009;NIKBAKHT BRUJENI et al, 2016). When BLV-infected animals were characterized into two profiles of infection -high and low proviral load (HPVL and LPVL respectively) (JULIARENA et al, 2007), BoLA DRB3.2 *0902 allele was the strongest associated with LPVL profile, while *1501 or 03 allele showed a significant association with HPVL in carrier animals (JULIARENA et al, 2008). Miyasaka et al (2013) also analyzed the effect of BoLA DRB3.2 alleles on proviral load in Japanese cattle and found that *0902 and *1101 alleles were associated with LPVL and *1601 allele with HPVL and identified BoLA class II haplotypes that correlated with different PVL status.…”