A New Messenger RNA Expressed by Bovine Leukemia Virus Infected Cells

Abstract Vaccination against retroviruses is a challenge because of their ability to stably integrate into the host genome, undergo long-term latency in a proportion of infected cells and thereby escape immune response. Since clearance of the virus is almost impossible once infection is established, the primary goal is to achieve sterilizing immunity. Besides efficacy, safety is the major issue since vaccination has been associated with increased infection or reversion to pathogenicity. In this review, we discuss the different issues that we faced during the development of an efficient vaccine against bovine leukemia virus (BLV). We summarize the historical failures of inactivated vaccines, the efficacy and safety of a live-attenuated vaccine and the economical constraints of further industrial development.

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Cellular distribution of bovine leukemia virus proteins gp51SU, Pr72env, and Pr66gag-pro in persistently infected cells

Virus Research ◽

10.1016/s0168-1702(01)00291-x ◽

2001 ◽

Vol 79 (1-2) ◽

pp. 47-57 ◽

Cited By ~ 4

Author(s):

Louie Llames ◽

Joaquin Goyache ◽

Ana Domenech ◽

Ana V Montaña ◽

Guillermo Suarez ◽

...

Keyword(s):

Bovine Leukemia Virus ◽

Leukemia Virus ◽

Cellular Distribution ◽

Persistently Infected ◽

Infected Cells ◽

Virus Proteins

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Trans activation of the bovine leukemia virus long terminal repeat in BLV-infected cells

Science ◽

10.1126/science.2981432 ◽

1985 ◽

Vol 227 (4684) ◽

pp. 320-322 ◽

Cited By ~ 49

Author(s):

C. Rosen ◽

J. Sodroski ◽

R Kettman ◽

A Burny ◽

W. Haseltine

Keyword(s):

Long Terminal Repeat ◽

Bovine Leukemia Virus ◽

Leukemia Virus ◽

Terminal Repeat ◽

Infected Cells

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Intestinal Shiga Toxin-Producing Escherichia coli Bacteria Mitigate Bovine Leukemia Virus Infection in Experimentally Infected Sheep

Infection and Immunity ◽

10.1128/iai.74.5.2906-2916.2006 ◽

2006 ◽

Vol 74 (5) ◽

pp. 2906-2916 ◽

Cited By ~ 13

Author(s):

Witold A. Ferens ◽

Rowland Cobbold ◽

Carolyn J. Hovde

Keyword(s):

Escherichia Coli ◽

Antiviral Activity ◽

Shiga Toxin ◽

Bovine Leukemia Virus ◽

Mononuclear Cells ◽

Leukemia Virus ◽

Average Weight ◽

E Coli ◽

Infected Cells ◽

The Impact

ABSTRACTRuminants often carry gastrointestinal Shiga toxin (Stx)-producingEscherichia coli(STEC). Stxs belong to a large family of ribosome-inactivating proteins (RIPs), found in many plants and some bacteria. Plant RIPs, secreted into extracellular spaces, limit the spread of viruses through plant tissues by penetrating and killing virally infected cells. Previously, we showed Stx activity against bovine leukemia virus (BLV)-infected cells in vitro and hypothesized that STEC bacteria have antiviral activity in ruminant hosts. Here, we investigated the impact of STEC on the initial phases of BLV infection in sheep. Sheep were treated with biweekly oral doses ofE. coliO157:H7 (an STEC) or an isogenicstxmutant strain. A different group of sheep were similarly treated with five naturally occurring ovine STEC isolates orstx-negativeE. coli. Intestinal STEC bacteria were enumerated and identified by standard fecal culture and DNA hybridization. Oral STEC treatment did not always result in carriage of STEC, although many animals consistently presented with >104CFU/g feces. BLV viremia was assessed by spontaneous lymphocyte proliferation (SLP) in cultures of blood mononuclear cells and by syncytium formation in cocultures of the same with F-81 indicator cells. SLP was lower (P< 0.05) and syncytia were fewer (P < 0.05) in STEC-treated sheep than in untreated sheep. Both lower SLP and fewer syncytia positively correlated with fecal STEC numbers. Average weight gain post-BLV challenge was higher in STEC-treated sheep than in untreated sheep (P< 0.05). These results support the hypothesis that in ruminants, intestinal STEC bacteria have antiviral activity and mitigate BLV-induced disease.

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Biosynthesis of bovine leukemia virus (BLV) major internal protein (p24) in infected cells andX. laevisoocytes microinjected with BLV 60-70S RNA

Archives Internationales de Physiologie et de Biochimie ◽

10.3109/13813457709053315 ◽

1977 ◽

Vol 85 (5) ◽

pp. 978-979 ◽

Cited By ~ 4

Author(s):

J. Ghysdael ◽

E. Hubert ◽

Y. Cleuter

Keyword(s):

Bovine Leukemia Virus ◽

Leukemia Virus ◽

Internal Protein ◽

Infected Cells

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Analysis of Nucleotide Sequence of Tax, miRNA and LTR of Bovine Leukemia Virus in Cattle with Different Levels of Persistent Lymphocytosis in Russia

Pathogens ◽

10.3390/pathogens10020246 ◽

2021 ◽

Vol 10 (2) ◽

pp. 246

Author(s):

Aneta Pluta ◽

Natalia V. Blazhko ◽

Charity Ngirande ◽

Thomas Joris ◽

Luc Willems ◽

...

Keyword(s):

Bovine Leukemia Virus ◽

Sequence Variation ◽

Leukemia Virus ◽

Lymphoproliferative Disease ◽

P Value ◽

Persistent Lymphocytosis ◽

Tax Protein ◽

Infected Cells ◽

The Relationship ◽

Bovine Species

Bovine Leukemia Virus (BLV) is the etiological agent of enzootic bovine leucosis (EBL), a lymphoproliferative disease of the bovine species. In BLV-infected cells, the long terminal repeat (LTR), the viral Tax protein and viral miRNAs promote viral and cell proliferation as well as tumorigenesis. Although their respective roles are decisive in BLV biology, little is known about the genetic sequence variation of these parts of the BLV genome and their impact on disease outcome. Therefore, the objective of this study was to assess the relationship between disease progression and sequence variation of the BLV Tax, miRNA and LTR regions in infected animals displaying either low or high levels of persistent lymphocytosis (PL). A statistically significant association was observed between the A(+187)C polymorphism in the downstream activator sequence (DAS) region in LTR (p-value = 0.00737) and high lymphocytosis. Our study also showed that the mutation A(−4)G in the CAP site occurred in 70% of isolates with low PL and was not found in the high PL group. Conversely, the mutations G(−133)A/C in CRE2 (46.7%), C(+160)T in DAS (30%) and A(310)del in BLV-mir-B4-5p, A(357)G in BLV-mir-B4-3p, A(462)G in BLV-mir-B5-5p, and GA(497–498)AG in BLV-mir-B5-3p (26.5%) were often seen in isolates with high PL and did not occur in the low PL group. In conclusion, we found several significant polymorphisms among BLV genomic sequences in Russia that would explain a progression towards higher or lower lymphoproliferation. The data presented in this article enabled the classification between two different genotypes; however, clear association between genotypes and the PL development was not found.

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The SU and TM Envelope Protein Subunits of Bovine Leukemia Virus Are Linked by Disulfide Bonds, both in Cells and in Virions

Journal of Virology ◽

10.1128/jvi.74.6.2930-2935.2000 ◽

2000 ◽

Vol 74 (6) ◽

pp. 2930-2935 ◽

Cited By ~ 38

Author(s):

Elizabeth R. Johnston ◽

Kathryn Radke

Keyword(s):

Envelope Protein ◽

Bovine Leukemia Virus ◽

Disulfide Bonds ◽

Noncovalent Interactions ◽

Leukemia Virus ◽

Envelope Proteins ◽

Protein Subunits ◽

Rous Sarcoma ◽

Infected Cells ◽

Polyprotein Precursor

ABSTRACT After the polyprotein precursor of retroviral envelope proteins is proteolytically cleaved, the surface (SU) and transmembrane (TM) subunits remain associated with each other by noncovalent interactions or by disulfide bonds. Disulfide linkages confer a relatively stable association between the SU and TM envelope protein subunits of Rous sarcoma virus and murine leukemia virus. In contrast, the noncovalent association between SU and TM of human immunodeficiency virus leads to significant shedding of SU from the surface of infected cells. The SU and TM proteins of bovine leukemia virus (BLV) initially were reported to be disulfide linked but later were concluded not to be, since TM is often lost during purification of SU protein. Here, we show that SU and TM of BLV do, indeed, associate through disulfide bonds, whether the envelope proteins are overexpressed in transfected cells, are produced in virus-infected cells, or are present in newly produced virions.

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Genetic Analysis of the pX Region in Bovine Leukemia Virus genotype 1 in Holstein Friesian Cattle with Different Stages of Infection

10.21203/rs.3.rs-570327/v1 ◽

2021 ◽

Author(s):

Neli Montero Machuca ◽

Jorge Luis Tórtora Pérez ◽

Ana Silvia González Méndez ◽

Lucia Angelica García-Camacho ◽

Ernesto Marín Flamand ◽

...

Keyword(s):

Bovine Leukemia Virus ◽

Proviral Load ◽

Leukemia Virus ◽

Genotype 1 ◽

Virus Genotype ◽

Blood Leukocytes ◽

Nucleotide Deletion ◽

Holstein Friesian ◽

Infected Cells ◽

Friesian Cattle

Abstract The pX genetic region of the Bovine Leukemia Virus (BLV) includes four genes with overlapping reading frames that code for the Tax, Rex, R3 and G4 proteins. These proteins are involved in the regulation of transcriptional and post-transcriptional viral expression, as well as having oncogenic potential. Our goal was to determine the pathogenic role associated with BLV genotype 1 pX region genetics in terms of lymphocytosis, lymphomas and proviral load. We screened 724 serological samples from mixed-age Holstein Friesian cattle from six states in Mexico. Once peripheral blood leukocytes were isolated from whole blood with anticoagulant, we extracted genomic DNA using a commercial kit. Then, we designed in silico primers that hybridize in conserved regions of the BLV pX region, which allowed for PCR standardization to detect proviral DNA in infected cells. Positive amplicons were sequenced using the Sanger method, obtaining 1156 nucleotide-long final sequences that included the four pX region genes. The 30 heads of cattle that formed the genetic study population included 12 with lymphocytosis, 12 without lymphocytosis and six with lymphoma. Lymphoma presence was determined in six bovine tumor tissues using histopathology, and we identified BLV presence with in situ hybridization.Phylogenetic analysis determined that the 30 sequences were associated with genotype 1, and genetic distance between the sequences ranged from 0.2% - 2.09%. We identified two sequences in the G4 gene, one with a three-nucleotide deletion (AGU_7488L, in a cow with lymphocytosis), and one with a nine nucleotide deletion (AGU_18A, in a cow without lymphocytosis). PX region analysis identified positive selection in the G4, rex and R3 genes, and we found no difference in proviral load between the studied groups. It was not possible to establish an association between pX region variability and the development of lymphocytosis, lymphoma, asymptomatic status and proviral load in BLV-infected cattle.

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