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

• Published in: Microbes and infection 2006-07, Vol.8 (8), p.2163-2171
• Main Authors: Konnai, Satoru, Usui, Tatsufumi, Ikeda, Manabu, Kohara, Junko, Hirata, Toh-ichi, Okada, Kosuke, Ohashi, Kazuhiko, Onuma, Misao
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; BLV; Bovine leukemia virus; Carrier State - virology; Cattle; Cell Line; Disease Progression; Enzootic Bovine Leukosis - genetics; Enzootic Bovine Leukosis - immunology; Enzootic Bovine Leukosis - virology; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Frequency; Leukemia Virus, Bovine; Lymphoma - genetics; Lymphoma - veterinary; Lymphoma - virology; Microbiology; Miscellaneous; Molecular Sequence Data; Polymorphism; Polymorphism, Genetic; Promoter; Promoter Regions, Genetic; Proviruses; RNA, Messenger - analysis; RNA, Messenger - genetics; Sequence Homology, Nucleic Acid; TNF-alpha; Transcriptional Activation; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Viral Load; Virology
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2006.04.017

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.