Abstract
Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. However, less than 5% of BLV-infected cattle will develop lymphoma, suggesting that, in addition to viral infection, host genetic polymorphisms might play a role in disease susceptibility. Bovine leukocyte antigen (BoLA)-DRB3 is a highly polymorphic gene associated with BLV proviral load (PVL) susceptibility. Due to the fact that PVL is positively associated with disease progression, it is believed that controlling PVL can prevent lymphoma development. Thus, many studies have focused on the relationship between PVL and BoLA-DRB3. Despite this, there is little information regarding the relationship between lymphoma and BoLA-DRB3. Furthermore, whether or not PVL-associated BoLA-DRB3 is linked to lymphoma-associated BoLA-DRB3 has not been clarified. Here, we investigated whether or not lymphoma-associated BoLA-DRB3 is correlated with PVL-associated BoLA-DRB3. We demonstrate that two BoLA-DRB3 alleles were specifically associated with lymphoma resistance (*010:01 and *011:01), but no lymphoma-specific susceptibility alleles were found; furthermore, two other alleles, *002:01 and *012:01, were associated with PVL resistance and susceptibility, respectively. In contrast, lymphoma and PVL shared two resistance-associated (DRB3*014:01:01 and *009:02) BoLA-DRB3 alleles. Interestingly, we found that PVL associated alleles, but not lymphoma associated alleles, are related with the anti-BLV gp51 antibody production level in cows. Overall, our study is the first to demonstrate that the BoLA-DRB3 polymorphism confers differential susceptibility to BLV-induced lymphoma and PVL.
Highlights
IntroductionWhose genome integrates with the host genome, proviral load (PVL) is an important risk factor of viruss-associated disease prediction [5,6]
Viral load in chronic infections with viruses, such as hepatitis B virus (HBV), hepatitis C virus (HCV), human T cell leukemia virus type 1 (HTLV-1), and human immunodeficiency virus type 1(HIV-1), has been reported to determine the likelihood of pathogenesis and disease progression [1,2,3,4].For retroviruses, whose genome integrates with the host genome, proviral load (PVL) is an important risk factor of viruss-associated disease prediction [5,6]
Bovine leukemia virus (BLV) is closely related to HTLV-1 and is the causative agent of enzootic bovine leukosis (EBL), a disease that is characterized by long-term symptoms, including persistent lymphocytosis (PL), which may culminate in B-cell lymphosarcoma [7,8]
Summary
Whose genome integrates with the host genome, proviral load (PVL) is an important risk factor of viruss-associated disease prediction [5,6]. Several studies indicate that BLV PVL is associated with BLV-related disease progression [9,10,11,12,13]. Only 5% of infected cattle progress to develop lymphoma, suggesting that in addition to viral infection, host genetic polymorphisms might play a role in disease susceptibility. The major histocompatibility complex (MHC), a highly polymorphic gene set, plays a crucial role in antigen presentation and immune responsiveness [14,15,16], and it is associated with numerous infectious diseases. Several studies have identified genetic variations in BoLA-DRB3, a functionally important locus and the most highly polymorphic BoLA class II locus in cattle. 330 DRB3 alleles have been registered in the Immuno Polymorphism Database (IPD)- MHC database
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