Tumor necrosis factor-alpha genetic polymorphism may contribute to progression of bovine leukemia virus-infection

In a previous report, we had indicated that in a sheep model, the expression of tumor necrosis factor (TNF)-α was closely associated with disease progression in sheep experimentally infected with bovine leukemia virus (BLV). However, individual variabilities are observed in these responses in BLV-infected animals. To attempt to identify genetic factors promoting the progression to BLV-induced lymphoma, we endeavored to determine whether there are any polymorphisms in the TNF-α gene among 291 individuals and whether this would affect the level of TNF-α expression and concomitant progression of BLV-induced disease or increase in the provirus load in the carriers. We found that the frequency of the TNF-α −824G allele, which has been associated with low transcription activity of the promoter/predicted enhancer region of the bovine TNF-α gene, was higher in individuals with BLV-induced lymphoma than in asymptomatic carrier individuals. In addition, we observed a tendency for increased BLV-provirus load in cattle with TNF-α −824G/G homozygote compared to TNF-α −824A/A homozygote or TNF-α −824A/G. These data suggest that the observed polymorphism in the promoter region of TNF-α gene could at least in part contribute to the progression of lymphoma in BLV-infection.