Induction and inhibition of bovine leukaemia virus expression in naturally infected cells

Zandomeni, Rubén; Carrera-Zandomeni, M.; Esteban, Eduardo; Donawick, William J.; Ferrer, Jorge F.

doi:10.1099/0022-1317-73-8-1915

Cited by 18 publications

(22 citation statements)

References 39 publications

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“…We also found a similar time-dependent loss of sensitivity of SLP to anti-gp51-mediated inhibition. Both of these findings are consistent with the fact that the expression of BLV particles in culture reaches maximum after 12 to 24 h of cell culture (57). Finally, we demonstrated that cell cultures treated with Stx1 express less BLV p24 protein.…”

Section: Discussionsupporting

confidence: 79%

Antiviral Activity of Shiga Toxin 1: Suppression of Bovine Leukemia Virus-Related Spontaneous Lymphocyte Proliferation

Ferens

Hovde

2000

Infect Immun

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Human infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) cause hemorrhagic colitis. The Stxs belong to a large family of ribosome-inactivating proteins (RIPs) that are found in a variety of higher plants and some bacteria. Many RIPs have potent antiviral activity for the plants that synthesize them. STEC strains, both virulent and nonvirulent to humans, are frequently isolated from healthy cattle. Interestingly, despite intensive investigations, it is not known why cattle carry STEC. We tested the hypothesis that Stx has antiviral properties for bovine viruses by assessing the impact of Stx type 1 (Stx1) on bovine peripheral blood mononuclear cells (PBMC) from cows infected with bovine leukemia virus (BLV). PBMC from BLV-positive animals invariably displayed spontaneous lymphocyte proliferation (SLP) in vitro. Stx1 or the toxin A subunit (Stx1A) strongly inhibited SLP. Toxin only weakly reduced the pokeweed mitogen-or interleukin-2-induced proliferation of PBMC from normal (BLV-negative) cows and had no effect on concanavalin A-induced proliferation. The toxin activity in PBMC from BLV-positive cattle was selective for viral SLP and did not abrogate cell response to pokeweed mitogen-or interleukin-2-induced proliferation. Antibody to virus or Stx1A was most effective at inhibiting SLP if administered at the start of cell culture, indicating that both reagents likely interfere with BLV-dependent initiation of SLP. Stx1A inhibited expression of BLV p24 protein by PBMC. A well-defined mutant Stx1A (E167D) that has decreased catalytic activity was not effective at inhibiting SLP, suggesting the inhibition of protein synthesis is likely the mechanism of toxin antiviral activity. Our data suggest that Stx has potent antiviral activity and may serve an important role in BLV-infected cattle by inhibiting BLV replication and thus slowing the progression of infection to its malignant end stage.

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Section: Discussionsupporting

confidence: 79%

Antiviral Activity of Shiga Toxin 1: Suppression of Bovine Leukemia Virus-Related Spontaneous Lymphocyte Proliferation

Ferens

Hovde

2000

Infect Immun

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“…Thus, both results argue in favour of a specific phosphorylation of CDC25B by CK2. To ensure that no contaminating kinase copurified with either in vitro translated CDC25B or recombinant CK2, kinase assays were performed in the presence of two CK2 inhibitors: heparin and DRB (5,6-dichloro-1-b-d-ribofuranosyl benzimidazole) (Zandomeni et al, 1986). Increasing concentration of heparin abolished CDC25B phosphorylation (Figure 2a) and addition of DRB considerably reduced its phosphorylation (Figure 2b).…”

Section: Resultsmentioning

confidence: 99%

Protein kinase CK2 regulates CDC25B phosphatase activity

et al. 2003

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Human dual-specificity phosphatases CDC25 (A, B and C) play an important role in the control of cell cycle progression by activating the cyclin-dependent kinases (CDKs). Regulation of these phosphatases during the cell cycle involves post-translational modifications such as phosphorylation and protein-protein interactions. Given the suspected involvement of the protein kinase CK2 at the G2/M transition, we have investigated its effects on the CDC25B phosphatase. We show that in vitro CK2 phosphorylates CDC25B, but not CDC25C. Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. We also report that CDC25B interacts with CK2, and this interaction, mediated by the CK2b regulatory subunit, involves domains that are located within the first 55 amino acids of CK2b and between amino acids 122 and 200 on CDC25B. This association was confirmed in vivo, in Sf9 insect cells and in U 2 OS human cells expressing an HA epitope-tagged CDC25B. Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo. We discuss the possibility that CDC25B phosphorylation by CK2 could play a role in the regulation of the activity of CDC25B as a starter of mitosis.

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“…Although BLV expression in vivo is thought to be blocked at the transcriptional level (4,29,44,72), little is known about specific cellular events responsible for this viral latency and the derepression after in vitro culture. A plasma-blocking factor present in some virus-infected animals could be implicated in the inhibition of viral synthesis in vivo (29,80). However, the nature of this factor and its mechanism of action have not yet been established.…”

mentioning

confidence: 99%

The CREB, ATF-1, and ATF-2 transcription factors from bovine leukemia virus-infected B lymphocytes activate viral expression

Adam¹,

Kerkhofs²,

Mammerickx³

et al. 1996

J Virol

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Efficient transcription and replication of the bovine leukemia virus (BLV) genome require both the viral long terminal repeat (LTR) and the virus-coded transcriptional activator Tax, which functions through a 21-bp sequence (Tax-responsive element [TxRE]) which is repeated three times within the LTR. Since Tax does not bind directly to DNA, host cell transcription factors play a central role in BLV expression. Electrophoretic mobility shift assays with nuclear extracts prepared with infected bovine B lymphocytes revealed fiveTxREspecific complexes (C1, C2, C3, C4, and C5). Here, by using a UV-induced indirect labeling technique (UV cross-linking) in conjunction with mobility shift assays, eight major polypeptides of 31, 33, 42, 46, 51, 57, 87, and 119 kDa were identified within these five complexes. Immunoprecipitation experiments identified the 57and 119-kDa proteins as cyclic AMP response element-binding (CREB) proteins, the 46-and 51-kDa proteins as activating transcription factor-1 (ATF-1), and the 87-kDa as protein ATF-2. All of these proteins (except the ATF-1 protein of 51 kDa) belong to the complex C1, which is the major complex identified in freshly isolated BLV-infected lymphocytes from cattle with persistent lymphocytosis. In transient-cotransfection experiments, these three transcription factors were able to activate LTR-directed gene expression in the presence of protein kinase A or Ca 2؉ /calmodulin-dependent protein kinase IV. CREB protein, ATF-1, and ATF-2 thus appear to be the major transcription factors involved in the early stages of viral expression.

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Induction and inhibition of bovine leukaemia virus expression in naturally infected cells

Cited by 18 publications

References 39 publications

Antiviral Activity of Shiga Toxin 1: Suppression of Bovine Leukemia Virus-Related Spontaneous Lymphocyte Proliferation

Antiviral Activity of Shiga Toxin 1: Suppression of Bovine Leukemia Virus-Related Spontaneous Lymphocyte Proliferation

Protein kinase CK2 regulates CDC25B phosphatase activity

The CREB, ATF-1, and ATF-2 transcription factors from bovine leukemia virus-infected B lymphocytes activate viral expression

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