Cis-drivers and trans-drivers of bovine leukemia virus oncogenesis.

Abstract:

:The bovine leukemia virus (BLV) is a retrovirus inducing an asymptomatic and persistent infection in ruminants and leading in a minority of cases to the accumulation of B-lymphocytes (lymphocytosis, leukemia or lymphoma). Although the mechanisms of oncogenesis are still largely unknown, there is clear experimental evidence showing that BLV infection drastically modifies the pattern of gene expression of the host cell. This alteration of the transcriptome in infected B-lymphocytes results first, from a direct activity of viral proteins (i.e. transactivation of gene promoters, protein-protein interactions), second, from insertional mutagenesis by proviral integration (cis-activation) and third, from gene silencing by microRNAs. Expression of viral proteins stimulates a vigorous immune response that indirectly modifies gene transcription in other cell types (e.g. cytotoxic T-cells, auxiliary T-cells, macrophages). In principle, insertional mutagenesis and microRNA-associated RNA interference can modify the cell fate without inducing an antiviral immunity. Despite a tight control by the immune response, the permanent attempts of the virus to replicate ultimately induce mutations in the infected cell. Accumulation of these genomic lesions and Darwinian selection of tumor clones are predicted to lead to cancer.

journal_name

Curr Opin Virol

authors

Safari R,Hamaidia M,de Brogniez A,Gillet N,Willems L

doi

10.1016/j.coviro.2017.06.012

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

15-19

eissn

1879-6257

issn

1879-6265

pii

S1879-6257(17)30052-4

journal_volume

26

pub_type

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