Bovine leukemia virus gene expression in vivo

Haas, Ludwig; Divers, Thomas J.; Casey, James W.

doi:10.1128/jvi.66.10.6223-6225.1992

Cited by 24 publications

(19 citation statements)

References 16 publications

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“…Expression of the BLV genome is repressed in vivo, and even sensitive methods, such as reverse transcription-PCR (RT-PCR) and in situ hybridization, have detected only limited viral RNA expression (2,26,30,37,42,63). However, the virus can be reactivated ex vivo, by growing untransformed BLVinfected lymphocytes from aleukemic sheep (31,39,42,50).…”

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In Vivo Rescue of a Silent tax -Deficient Bovine Leukemia Virus from a Tumor-Derived Ovine B-Cell Line by Recombination with a Retrovirally Transduced Wild-Type tax Gene

Broeke

Bagnis

Ciesiolka

et al. 1999

J Virol

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The lack of bovine leukemia virus (BLV) expression is a consistent finding in freshly isolated ovine tumor cells and in the B-cell lines derived from these tumors. In order to gain further insight into the mechanisms of BLV silencing in these tumors, we have used the YR2 B-cell line, which was derived from the leukemic cells of a BLV-infected sheep. This cell line contains a single, monoclonally integrated, silent provirus, which cannot be reactivated either by stimulation in vitro or by in vivo injection of the tumor cells or cloned proviral DNA in sheep. Sequence analysis of the tax gene from the YR2 cell line identified two G-to-A transitions (G 7924 to A 7924 and G 8149 to A 8149 ) that result in E-to-K amino acid changes at positions 228 and 303 in the Tax protein.Following retroviral vector-mediated transfer of a wild-type tax gene into YR2 cells, we showed that BLV mRNA, viral proteins, and virions were produced, demonstrating that the cellular factors required for virus expression were present in the original YR2 cell line. Injection of this transduced YR2 cell line in sheep led to the rescue of replication-competent BLV proviruses. The integrated competent proviruses exhibited unique chimeric tax genes, which arose from homologous recombination between the transduced wild-type tax and the YR2-derived tax sequences. Furthermore, in one of these functional recombinant proviruses, only the A 8149 -to-G 8149 reversion was present, providing clear evidence that the defect underlying the silent phenotype in YR2 cells results from a single C-terminal E 303 -to-K 303 amino acid substitution in the BLV Tax protein. Our observations suggest that a single strategically located mutation in tax provides a mechanism for BLV inactivation in B-cell tumors.

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In Vivo Rescue of a Silent tax -Deficient Bovine Leukemia Virus from a Tumor-Derived Ovine B-Cell Line by Recombination with a Retrovirally Transduced Wild-Type tax Gene

Broeke

Bagnis

Ciesiolka

et al. 1999

J Virol

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“…The proportion of lymphocytes carrying provirus in PL animals is 33 to 77% (27,34), while less than 1% of lymphocytes from AL animals carry provirus (34). Viral transcripts (18,24) and virus expression in vitro (10,11) are detected most readily in PL and TB cells and only infrequently in from AL cells. Thus, our findings provide compelling evidence that less-stringent virus control in PL and TB animals correlates with impaired CD4 ϩ T-cell immunity and that the immune system likely influences the fate of infection.…”

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confidence: 99%

Progression to persistent lymphocytosis and tumor development in bovine leukemia virus (BLV)-infected cattle correlates with impaired proliferation of CD4+ T cells in response to gag- and env-encoded BLV proteins

Orlik

Splitter

1996

J Virol

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The mechanism of leukemogenesis and persistent lymphocytosis (PL; benign expansion of B lymphocytes) in cattle infected with bovine leukemia virus (BLV; a retrovirus closely related to human T-cell leukemia virus type 1) is unknown; however, the immune system likely plays an important role in controlling the outcome of infection. In this study, we compared T-cell competence in serologically positive alymphocytotic (AL) animals with T-cell functions in animals with progressive stages of infection, PL and tumor bearing (TB). Dramaticdifferences were observed in lymphocyte proliferation to recombinant proteins encoded by BLV gag (p12, p15, and p24) and env (gp30, and gp51) genes in different disease stages. Lymphocytes from AL cattle recognized an average of three of five recombinant proteins per animal. Expansion of antigen pulsed lymphocytes in interleukin-2 increased protein recognition to almost five per animal. In contrast, lymphocytes from PL and TB animals failed to recognize any BLV recombinant proteins. Short-term T-cell cultures from the PL group expanded in interleukin-2, as well as the PL and TB cells cultured in indomethacin (3 to 6 g/ml), increased the average of recognized proteins per animal to one. Cells proliferating to BLV antigens were CD4 ؉ T lymphocytes, as shown by cell depletion studies. The positive effect of indomethacin suggests involvement of prostaglandin E 2 as a negative regulatory factor in the later stages of disease. Thus, for the first time, advancing stages of BLV infection were correlated with decreased T-cell competence, providing deeper insight into pathogenesis of retroviral infections.

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“…This has made it difficult to identify a discrete mechanism by which BLV can mediate leukemogenesis. Amplification by reverse transcriptase PCR (RT-PCR) has detected BLV mRNAs in freshly isolated peripheral blood mononuclear cells (PBMC) and tumor cells of infected animals (1,18,19,23,38). Overt virus expression occurs upon cultivation of these cells in vitro.…”

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