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Bovine leukemia virus pre-miRNA genes' polymorphism.

ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs with a wide distribution in nature among the living things. They play a key role both in normal signaling pathways and in pathological ones. Bovine leukemia virus (BLV) is an oncogenic retrovirus of Deltaretrovirus genus causing persistent infection in its natural hosts - cattle, zebu and water buffalo with diverse clinical manifestations through the defeat of B-lymphocytes (B-cells). Ten BLV encoded miRNAs (further miRs-B) transcribed from five different pre-miRNA (further pre-miR-B) genes are abundantly detected in BLV infected B-cells. Here we report about several alleles of each of pre-miRs-B' genes, some of which have a highly significant association with an increase or a decrease of the number of leukocytes (WBCs - white blood cells) in BLV-infected cows.

SUBMITTER: Zyrianova IM

PROVIDER: S-EPMC6333434 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Bovine leukemia virus pre-miRNA genes' polymorphism.

Zyrianova I M IM Koval'chuk S N SN

RNA biology 20180101 12

MicroRNAs (miRNAs) are small non-coding RNAs with a wide distribution in nature among the living things. They play a key role both in normal signaling pathways and in pathological ones. Bovine leukemia virus (BLV) is an oncogenic retrovirus of Deltaretrovirus genus causing persistent infection in its natural hosts - cattle, zebu and water buffalo with diverse clinical manifestations through the defeat of B-lymphocytes (B-cells). Ten BLV encoded miRNAs (further miRs-B) transcribed from five diffe ...[more]

PMID: 30513054

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Project description:BACKGROUND:Bovine leukemia virus (BLV), which is closely related to human T-cell leukemia virus, is the etiological agent of enzootic bovine leukosis, a disease characterized by a highly prolonged course involving persistent lymphocytosis and B-cell lymphoma. The bovine major histocompatibility complex class II region plays a key role in the subclinical progression of BLV infection. In this study, we aimed to evaluate the roles of CD4+ T-cell epitopes in disease progression in cattle. METHODS:We examined five Japanese Black cattle, including three disease-susceptible animals, one disease-resistant animal, and one normal animal, classified according to genotyping of bovine leukocyte antigen (BoLA)-DRB3 and BoLA-DQA1 alleles using polymerase chain reaction sequence-based typing methods. All cattle were inoculated with BLV-infected blood collected from BLV experimentally infected cattle and then subjected to CD4+ T-cell epitope mapping by cell proliferation assays. RESULTS:Five Japanese Black cattle were successfully infected with BLV, and CD4+ T-cell epitope mapping was then conducted. Disease-resistant and normal cattle showed low and moderate proviral loads and harbored six or five types of CD4+ T-cell epitopes, respectively. In contrast, the one of three disease-susceptible cattle with the highest proviral load did not harbor CD4+ T-cell epitopes, and two of three other cattle with high proviral loads each had only one epitope. Thus, the CD4+ T-cell epitope repertoire was less frequent in disease-susceptible cattle than in other cattle. CONCLUSION:Although only a few cattle were included in this study, our results showed that CD4+ T-cell epitopes may be associated with BoLA-DRB3-DQA1 haplotypes, which conferred differential susceptibilities to BLV proviral loads. These CD4+ T-cell epitopes could be useful for the design of anti-BLV vaccines targeting disease-susceptible Japanese Black cattle. Further studies of CD4+ T-cell epitopes in other breeds and using larger numbers of cattle with differential susceptibilities are required to confirm these findings.

Project description:BackgroundThe absence of virus expression during the chronic stage of bovine leukemia virus (BLV) infection and its reactivation upon ex vivo culture has become a long-lived Dogma. During the chronic stage of BLV infection the immune response limits viral replication and the mitotic division of latently infected cells, carrying BLV provirus, allows viral expansion and disease progression towards a lymphoproliferative disorder. Several stressor factors have been associated with animal production and handling. As natural mediator of stress, glucocorticoids are strong immunosuppressive agents; moreover, they can bind long-terminal repeat region of retroviruses and induce viral expression. In the present study, we present a case report describing the spontaneous reactivation of BLV infection in naturally infected cattle.Case presentationIn order to investigate if virus reactivation occurred in vivo during the course of BLV infection, we followed up for 328 days one Holstein cow (> 3 years) chronically infected with BLV which presented high-proviral loads. This animal was neither lactating nor pregnant. Furthermore, we investigated if a stressor stimulus, in this case the administration of a synthetic glucocorticoid (dexamethasone), could impact the course of BLV infection in three additional cattle. For the first time, we observed a high level of BLV transcripts in a total of four cattle chronically infected with BLV. The detection of viral transcripts corresponding to pol gene strongly suggests virus reactivation in these animals. Interestingly, this simultaneous virus reactivation was unrelated to dexamethasone treatment.ConclusionsWe reported for the first time spontaneous and high level of BLV transcriptional activation in cattle chronically infected with BLV. Although virus reactivation was unrelated to dexamethasone treatment, other stressor stimuli might have influenced this outcome. Future studies will be necessary to understand these observations, since the spontaneous virus reactivation presented here might have implications on BLV pathogenesis and transmission.

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Bovine leukemia virus pre-miRNA genes' polymorphism.

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Bovine leukemia virus pre-miRNA genes' polymorphism.

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