T cell proliferative response to bovine leukaemia virus (BLV): identification of T cell epitopes on the major core protein (p24) in BLV-infected cattle with normal haematological values

Mager, A.; Masengo, R; Mammerickx, Marc; Letesson, J.J.

doi:10.1099/0022-1317-75-9-2223

Cited by 30 publications

(20 citation statements)

References 40 publications

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“…Peripheral blood mononuclear cells (PBMCs) were purified from the blood samples by density gradient centrifugation on Percoll (GE Healthcare), washed three times with PBS, and suspended in PBS. Isolated PBMCs were then labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) (Sigma-Aldrich) and cultured in triplicate with 2% heat-inactivated culture supernatant of BLV-infected fetal lamb kidney (FLK) cells (41) or BLV gp51 peptide mix [0.1 and 1 µg/ml of each peptide (25)] for 6 days. The heat-inactivated culture supernatant of BLV-uninfected FLK cells was used as a negative control antigen.…”

Section: Methodsmentioning

confidence: 99%

Anti-Bovine Programmed Death-1 Rat–Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle

et al. 2017

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Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1), is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat–bovine chimeric monoclonal antibody 5D2 (Boch5D2) was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV). Purified Boch5D2 was capable of detecting bovine PD-1 molecules expressed on cell membranes in flow cytometric analysis. In particular, Biacore analysis determined that the binding affinity of Boch5D2 to bovine PD-1 protein was similar to that of the original anti-bovine PD-1 rat monoclonal antibody 5D2. Boch5D2 was also capable of blocking PD-1/PD-L1 binding at the same level as 5D2. The immunomodulatory and therapeutic effects of Boch5D2 were evaluated by in vivo administration of the antibody to a BLV-infected calf. Inoculated Boch5D2 was sustained in the serum for a longer period. Boch5D2 inoculation resulted in activation of the proliferation of BLV-specific CD4+ T cells and decrease in the proviral load of BLV in the peripheral blood. This study demonstrates that Boch5D2 retains an equivalent biochemical function to that of the original antibody 5D2 and is a candidate therapeutic agent for regulating antiviral immune response in vivo. Clinical efficacy of PD-1/PD-L1 blockade awaits further experimentation with a large number of animals.

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Section: Methodsmentioning

confidence: 99%

Anti-Bovine Programmed Death-1 Rat–Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle

et al. 2017

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“…The CA protein appears to be a major target for the host immune response with high antibody titers found in the sera of infected animals and two defined regions of p24 being recognized by specific T lymphocytes [110,111]. One of the T-cell epitopes overlaps with a domain highly conserved among retroviruses, the major homology region (MHR), which is required for viral infectivity in vivo [112].…”

Section: The Blv Genomementioning

confidence: 99%

Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human

et al. 2007

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In 1871, the observation of yellowish nodules in the enlarged spleen of a cow was considered to be the first reported case of bovine leukemia. The etiological agent of this lymphoproliferative disease, bovine leukemia virus (BLV), belongs to the deltaretrovirus genus which also includes the related human T-lymphotropic virus type 1 (HTLV-1). This review summarizes current knowledge of this viral system, which is important as a model for leukemogenesis. Recently, the BLV model has also cast light onto novel prospects for therapies of HTLV induced diseases, for which no satisfactory treatment exists so far.

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“…A fourth residue (either Tyr or Phe) at position 147 appears to be invariably aromatic. These sequences also overlap a T cell epitope that is recognized in bovine leukaemia virus (BLV)-infected animals (Majer et al, 1994). In fact, purified p24 capsid protein stimulates the incorporation of [$H]methyl-thymidine into CD4 + -and CD8 + -enriched T cell populations.…”

mentioning

confidence: 99%

The major homology region of bovine leukaemia virus p24gag is required for virus infectivity in vivo.

Willems¹,

Kerkhofs²,

Attenelle³

et al. 1997

Journal of General Virology

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In order to gain insight into the role of the major homology region (MHR) in the infectious potential of bovine leukaemia virus (BLV), mutations were introduced into the capsid gene of an infectious molecular clone. A provirus that was designed to contain only a slightly modified version of the MHR (substitution of phenylalanine 147 with a tyrosine) was still infectious in vivo. Furthermore, the provirus loads were not significantly different from those obtained with a wild-type virus. A second mutant was designed to analyse a mild modification of the MHR at the level of arginine 150. The substitution of this residue with a lysine completely destroyed the infectious potential of the recombinant virus. Finally, a third mutant that was deleted in the MHR region was unable to infect the host. Thus it appears that the integrity of the MHR domain is essential for BLV infectivity in vivo.

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T cell proliferative response to bovine leukaemia virus (BLV): identification of T cell epitopes on the major core protein (p24) in BLV-infected cattle with normal haematological values

Cited by 30 publications

References 40 publications

Anti-Bovine Programmed Death-1 Rat–Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle

Anti-Bovine Programmed Death-1 Rat–Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle

Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human

The major homology region of bovine leukaemia virus p24gag is required for virus infectivity in vivo.

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