scholarly journals Bovine Leukemia Virus Structural Gene Vectors Are Immunogenic and Lack Pathogenicity in a Rabbit Model

1999 ◽  
Vol 73 (10) ◽  
pp. 8160-8166 ◽  
Author(s):  
Lucia Kucerova ◽  
Veronika Altanerova ◽  
Cestmir Altaner ◽  
Kathleen Boris-Lawrie
Keyword(s):  
Structural Gene ◽  
Bovine Leukemia Virus ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Rabbit Model ◽  
Sudden Onset ◽  
Negative Control ◽  
Peripheral Blood Mononuclear ◽  
In Vivo Transfection

ABSTRACT Infection with a replication-competent bovine leukemia virus structural gene vector (BLV SGV) is an innovative vaccination approach to prevent disease by complex retroviruses. Previously we developed BLV SGV that constitutively expresses BLV gag, pol, and env and related cis-acting sequences but lacks tax, rex, RIII, andGIV and most of the BLV long terminal repeat sequences, including the cis-acting Tax and Rex response elements. The novel SGV virus is replication competent and replicates a selectable vector to a titer similar to that of the parental BLV in cell culture. The overall goal of this study was to test the hypothesis that infection with BLV SGV is nonpathogenic in rabbits. BLV infection of rabbits by inoculation of cell-free BLV or cell-associated BLV typically causes an immunodeficiency-like syndrome and death by 1 year postinfection. We sought to evaluate whether in vivo transfection of BLV provirus recapitulates pathogenic BLV infection and to compare BLV and BLV SGV with respect to infection, immunogenicity, and clinical outcome. Three groups of rabbits were subjected to in vivo transfection with BLV, BLV SGV, or negative control DNA. The results of our 20-month study indicate that in vivo transfection of rabbits with BLV recapitulates the fatal BLV infection produced by cell-free or cell-associated BLV. The BLV-infected rabbits exhibited sudden onset of clinical decline and immunodeficiency-like symptoms that culminated in death. BLV and BLV SGV infected peripheral blood mononuclear cells and induced similar levels of seroconversion to BLV structural proteins. However, BLV SGV exhibited a reduced proviral load and did not trigger the immunodeficiency-like syndrome. These results are consistent with the hypothesis that BLV SGV is infectious and immunogenic and lacks BLV pathogenicity in rabbits, and they support the use of this modified proviral vector delivery system for vaccines against complex retroviruses like BLV.

scholarly journals Bovine Leukemia Virus-Induced Persistent Lymphocytosis in Cattle Does Not Correlate with Increased Ex Vivo Survival of B Lymphocytes

1999 ◽  
Vol 73 (2) ◽  
pp. 1127-1137 ◽  
Author(s):  
Franck Dequiedt ◽  
Glenn H. Cantor ◽  
Valerie T. Hamilton ◽  
Suzanne M. Pritchard ◽  
William C. Davis ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Bovine Leukemia Virus ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Leukemia Virus ◽  
Spontaneous Apoptosis ◽  
Persistent Lymphocytosis ◽  
Peripheral Blood Mononuclear

ABSTRACT Bovine leukemia virus (BLV) is an oncogenic retrovirus associated with B-cell lymphocytosis, leukemia, and lymphosarcoma in the ovine and bovine species. We have recently reported that in sheep, BLV protects the total population of peripheral blood mononuclear cells (PBMCs) from ex vivo spontaneous apoptosis. This global decrease in the apoptosis rates resulted from both direct and indirect mechanisms which allow extension of cell survival. Although sheep are not natural hosts for BLV, these animals are prone to develop virus-induced leukemia at very high frequencies. Most infected cattle, however, remain clinically healthy. This difference in the susceptibilities to development of leukemia in these two species might be related to alterations of the apoptotic processes. Therefore, we designed this study to unravel the mechanisms of programmed cell death in cattle. We have observed that PBMCs from persistently lymphocytotic BLV-infected cows were more susceptible to spontaneous ex vivo apoptosis than cells from uninfected or aleukemic animals. These higher apoptosis rates were the consequence of an increased proportion of B cells exhibiting lower survival abilities. About one-third of the BLV-expressing cells did not survive the ex vivo culture conditions, demonstrating that viral expression is not strictly associated with cell survival in cattle. Surprisingly, culture supernatants from persistently lymphocytotic cows exhibited efficient antiapoptotic properties on both uninfected bovine and uninfected ovine cells. It thus appears that indirect inhibition of cell death can occur even in the presence of high apoptosis rates. Together, these results demonstrate that the protection against spontaneous apoptosis associated with BLV is different in cattle and in sheep. The higher levels of ex vivo apoptosis occurring in cattle might indicate a decreased susceptibility to development of leukemia in vivo.

scholarly journals Cell-free transmission of Fv-4 resistance gene product controlling Friend leukemia virus-induced leukemogenesis: a unique mechanism for interference with viral infection

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1557-1563 ◽  
Author(s):  
M Kitagawa ◽  
S Aizawa ◽  
H Kamisaku ◽  
H Ikeda ◽  
K Hirokawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Specific Binding ◽  
Leukemia Virus ◽  
Spleen Cells ◽  
Peripheral Blood Mononuclear ◽  
Friend Leukemia ◽  
Bone Marrow Chimeras ◽  
Friend Leukemia Virus

Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We previously demonstrated that mixed radiation bone marrow chimeras containing Fv-4r-bearing BALB/c-Fv- 4Wr (C4W) bone marrow and Fv-4r-bearing C3H/He (C3H) bone marrow grafted into C3H recipient mice (C4W+C3H-->C3H) were resistant to Friend leukemia virus (FLV)-induced leukemogenesis, even when they contained as high as 70% C3H-derived cells. This indicates that FLV- sensitive C3H-derived cells are rendered refractory to infection and/or transformation with FLV when they coexist in mice with Fv-4r-bearing cells. To investigate the mechanism of Fv-4 resistance to FLV-induced leukemogenesis, we first examined the expression of Fv-4r env antigen in the peripheral blood mononuclear cells (PBMC) of these chimeras. The Fv-4r env antigen was present not only on C4W-derived cells, but also on Fv-4r-bearing C3H-derived cells in C4W+C3H-->C3H mixed bone marrow chimeras. The Fv-4r env antigen that binds to the cells surface of C3H cells was found in sera from normal C4W mice, C4W-->C3H chimeras, and C4W+C3H-->C3H mixed chimeras. The serum Fv-4r env antigen binds to ecotropic MuLV receptors, shown by specific binding to transfectant mink cells expressing ecotropic MuLV receptor, but not to parental mink cells. To determine whether the binding of Fv-4r env antigen to the putative MuLV receptors would block FLV infection, C3H thymocytes or spleen cells that had been preincubated with C4W serum were mixed with FLV and the subsequent production of MuLV specific antigens was examined. C3H thymocytes or spleen cells treated with C4W serum became refractory to binding by FLV. These results provide evidence that the Fv-4r env antigen is released from C4W-derived cells in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with FLV. The implication of these findings for gene therapy of retrovirus-induced disease such as acquired immune deficiency syndrome (AIDS) is discussed.

scholarly journals Cellular Immune Response to Interferon-Τ in Peripheral Blood Mononuclear Cells of Japanese Black Cattle with Bovine Leukemia Virus Infection / Imunski Odgovor Mononuklearnih Ćelija Periferne Krvi Na Interferon-Τ Kod Infekcije Virusom Leukemije Japanskog Crnog Govečeta

2015 ◽  
Vol 65 (2) ◽  
pp. 287-296
Author(s):  
Kakinuma Sei-Ichi ◽  
Izawa Tomohiro ◽  
Matsuda Kei-Ichi ◽  
Konnai Satoru ◽  
Maeda Yosuke ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Bovine Leukemia Virus ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Healthy Cattle ◽  
Blood Mononuclear Cells ◽  
Cellular Immune

γ IFN-τ is a type I interferon, and it is known to be non-virus inducible in ruminants. IFN-τ reduced syncytium formation by PBMC obtained from BLV infected cattle in vitro. In order to clarify the effects of IFN-τ on cellular immune function in Japanese Black (JB) cattle with bovine leukemia virus (BLV) infection, immune related factors of peripheral blood mononuclear cells (PBMC) were analyzed using IFN-τ as a stimulator. Thirty-two JB cattle were used in this investigation, and these cattle were divided into three groups: cattle with enzootic bovine leucosis (EBL) (EBL Group, N=7), clinically healthy cattle with BLV infection (Carrier Group, N=13), and clinically healthy cattle without BLV infection (non-Carrier Group, N=12). A number of mRNA expressions of interleukin-12 and interferon (IFN)-as immune cell activating cytokines, perforin and granulysin as cytotoxic factors, and myxovirus resistance protein (MX)-1 and MX-2 as anti-virus factors of PBMC were analyzed after culturing cells with phytohemagglutinin (PHA) or IFN-τ. The basal mRNA levels of perforin and granulysin in the Carrier Group were significantly higher than those in the non-Carrier Group. Also, significantly higher basal mRNA levels of MX-1 and MX-2 in the EBL Group were detected compared with the non-Carrier Group. The mRNA expressions of perforin and granulysin in PBMC stimulated with PHA were higher in the Carrier Group than those in the non-Carrier Group. There were significantly higher mRNA levels of MX-1 and MX-2 in PBMC stimulated with IFN-τ in the EBL Group compared with those in the non-Carrier Group. These results suggest an enhanced sensitivity of anti-virus reaction in PBMC by IFN-τ treatment in JB cattle with EBL.

scholarly journals Isolation of a Bovine Plasma Fibronectin-Containing Complex Which Inhibits the Expression of Bovine Leukemia Virus p24

2005 ◽  
Vol 79 (13) ◽  
pp. 8164-8170 ◽  
Author(s):  
Marianne J. van den Heuvel ◽  
Barbara J. Jefferson ◽  
Robert M. Jacobs
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Bovine Leukemia Virus ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Biologically Active ◽  
Peripheral Blood Mononuclear ◽  
Adult Cattle ◽  
Bovine Plasma ◽  
Blood Mononuclear Cells

ABSTRACT Bovine leukemia virus (BLV) is a deltaretrovirus that infects cattle worldwide. In agriculturally intensive regions, approximately 30% of dairy cows are BLV infected. Like the human T-cell leukemia virus (HTLV), there is a lengthy period of viral quiescence after initial infection with BLV. Unlike HTLV, BLV resides predominantly in B cells. Lymphoma is observed in less than 10% of BLV-infected adult cattle. Although viremia is undetectable in vivo, BLV-infected peripheral blood mononuclear cells readily become productive when cultured in vitro. Productivity is markedly diminished when cultures are supplemented with bovine plasma. This inhibitory activity of bovine plasma has been attributed to the “plasma blocking factor” (PBF). Here, we describe the purification of a PBF whose activity was resistant to heating to 65°C for 10 min and was attributable to a fibronectin-containing complex of approximately 320 kDa under nonreducing conditions. By use of two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time of flight (mass spectrometry), a protein with a size of 220 kDa and a pI of 5.4 was identified as a member of the fibronectin group of molecules. Both the purified protein and the commercially available bovine fibronectin inhibited BLV production in naturally infected peripheral blood mononuclear cells, although the fibronectin was less biologically active.

scholarly journals Global Genetic Profiles of Gene Network Disruption in Bovine Peripheral Blood Mononuclear Cells Induced by Bovine Leukemia Virus (BLV) Infection

2009 ◽  
Vol 2 ◽  
pp. GEG.S2853 ◽  
Author(s):  
Congjun Li ◽  
Robert W. Li ◽  
Theodore H. Elsasser ◽  
Stanislaw Kahl
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Bovine Leukemia Virus ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Viral Latency ◽  
Global Gene Expression ◽  
Immune Defense ◽  
Host Cells ◽  
Peripheral Blood Mononuclear

Efficient nutrient assimilation into useful animal-derived products is the ultimate requirement for successful animal production. Infection in young growing animals can decrease energy and nutrient use required for growth rate by redirection of nutrients to support immune defense processes. Bovine leukemia virus (BLV) infection is prevalent in several regions of the world including the U.S. Most BLV infections are characterized by viral latency in the majority of infected cells. Few, if any, definitive studies in cattle have addressed the potential perturbations of gene expression induced in host cells by BLV infection. This study uses integrated global gene expression information and knowledge of the regulatory events in cells to identify transcription regulation networks that control peripheral blood mononuclear cell (PBMC) responses to BLV infection. The aim is to identify the molecular and cellular pathway responses that are functioning during the viral latency stage of BLV infection. The data and regulatory network analysis indicate that CDC25A and transcription factors such as STAT1 and STAT3 may serve as important signaling pathways for the BLV-induced cellular responses. These findings provide vital information for the functional role of genes that participate in PBMC responses to BLV infection and pinpoint these newly characterized genes as potential molecular targets and biomarkers for animal infectious diseases.

scholarly journals Interleukin-12 p40 mRNA Expression in Bovine Leukemia Virus-Infected Animals: Increase in Alymphocytosis but Decrease in Persistent Lymphocytosis

1998 ◽  
Vol 72 (8) ◽  
pp. 6917-6921 ◽  
Author(s):  
Dohun Pyeon ◽  
Gary A. Splitter
Keyword(s):  
Mrna Expression ◽  
Bovine Leukemia Virus ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Antagonistic Effect ◽  
Interleukin 12 ◽  
Persistent Lymphocytosis ◽  
Peripheral Blood Mononuclear ◽  
Stage Disease ◽  
Bovine Leukosis

ABSTRACT Interleukin-12 (IL-12), a key cytokine in immune regulation, has an important role in activating the cell-mediated immune response in infectious diseases. Recently, a dichotomy between IL-12 and IL-10 regarding progression of a variety diseases has emerged. IL-12 activates type 1 cytokine production and has an antagonistic effect on type 2 cytokines. Here, by using quantitative competitive PCR, we show that peripheral blood mononuclear cells from bovine leukemia virus-infected animals in the alymphocytotic stage of disease express an increased amount of IL-12 p40 mRNA. In contrast, IL-12 p40 mRNA expression by cells from animals with late-stage disease, termed persistent lymphocytosis, was significantly decreased compared to that by normal and alymphocytotic animals. Interestingly, IL-12 p40 mRNA was also detected in tumor-bearing animals. IL-12 p40 expression occurred only in monocytes/macrophages, not B or T lymphocytes. The present study combined with previous findings suggest that IL-12 in bovine leukemia virus-infected animals may regulate production of other cytokines such as gamma interferon and IL-10 and the progression of bovine leukosis in animals that develop more advanced disease such as a persistent lymphocytosis of B cells or B-cell lymphosarcoma.

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