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

Abstract

Running title: Analysis of TNF-a genetic polymorphism and its effect on BLV-disease progressionCorrespondent footnote: * Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.Phone: konnai@vetmed.hokudai.ac.jp 2 AbstractIn 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, the 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 of 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.

Tumor necrosis factor-alpha (TNFα) gene polymorphism and expression of membrane-bound TNFα protein on CD11b+ and IgM+ cells in cows naturally infected with bovine leukemia virus

“…Further work is required to validate the above observation. The presence of correlations between the TNFα -824G allele and high proviral load was reported by other authors (Konnai et al 2006). In published studies, a higher frequency of the G/G genotype was noted in cows at clinical stages of LS than in individuals with subclinical form of AL.…”

“…Konnai et al (2006) demonstrated that SNP (Single Nucleotide Polymorphism) at position -824 A>G of the TNFα gene (promoter infections in cattle can be caused by SNPs in the region of cytokine-coding genes (Tsukasaki et al 2001, Nishimura et al 2003. The effect of the above genetic polymorphism on BLV infections and EBL progression in cattle remains weakly investigated.…”

Relationships Between the First Ovulation Postpartum and Polymorphism in Genes Relating to Function of Immunity, Metabolism and Reproduction in High-producing Dairy Cows

“…Indeed, polymorphisms in the TNFα gene have been associated with increased susceptibility to autoimmune and infectious diseases in mice [31] and humans [32] and bovine leukemia virus-induced disease [33]. In the present study, the occurrence of first postpartum ovulation within 3 weeks in the C/C genotype animals of TNFα exon (55.4%) was higher than that in T/ T genotypes (14.3%).…”

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

“…Concerning BLV infection, TNF-α is closely related with the immune response against viral dissemination, stimulating the elimination of infected lymphocytes (KABEYA et al, 1999). Konnai et al (2006) described that genotype G/G in position -824 of the promoter region of TNF-α was associated with low transcriptional activity of the promoter region. The frequency of this genotype G/G was higher in individuals with BLV-induced lymphoma than in asymptomatic carrier individuals.…”