A detailed molecular analysis of complete Bovine Leukemia Virus genomes isolated from B-cell lymphosarcomas

Abstract

It is widely accepted that the majority of cancers result from multiple cellular events leading to malignancy after a prolonged period of clinical latency, and that the immune system plays a critical role in the control of cancer progression. Bovine leukemia virus (BLV) is an oncogenic member of the Retroviridae family. Complete genomic sequences of BLV strains isolated from peripheral blood mononuclear cells (PBMC) from cattle have been previously reported. However, a detailed characterization of the complete genome of BLV strains directly isolated from bovine tumors is much needed in order to contribute to the understanding of the mechanisms of leukemogenesis induced by BLV in cattle. In this study, we performed a molecular characterization of BLV complete genomes from bovine B-cell lymphosarcoma isolates. A nucleotide substitution was found in the glucocorticoid response element (GRE) site of the 5' long terminal repeat (5'LTR) of the BLV isolates. All amino acid substitutions in Tax previously found to be related to stimulate high transcriptional activity of 5'LTR were not found in these studies. Amino acid substitutions were found in the nucleocapsid, gp51 and G4 proteins. Premature stop-codons in R3 were observed. Few mutations or amino acid substitutions may be needed to allow BLV provirus to achieve silencing. Substitutions that favor suppression of viral expression in malignant B cells might be a strategy to circumvent effective immune attack.

Molecular detection of bovine leukemia virus in peripheral blood of Iranian cattle, camel and sheep

“…The genome organization of BLV is similar to that of other retroviruses, where the structural proteins required for the production of infectious virions (from 5'to 3') includes the gag (encodes p24 and p15), pro (encodes protease), pol (encodes polymerase) and env (encodes gp51 and gp30) gene proteins (Momtaz 2010, Moratorio et al 2013. The BLV enveloped (env) gene coding for gp51 is highly conserved and both the gene and the antigen are present in the whole infected animal throughout the course of infection (OIE 2012).…”

Distribution of Potential Non-Canonical DNA Motif in Proviral DNA Genes of the Avian Influenza and Bovine Leukemia Retroviruses

“…According to data obtained by Moratorio et al (2013), who were the first to describe in significant detail all amino acid sequences of the BLV proteins, it is possible to see that 34 overlapping variants of potential G-quadruplexes located between nucleotides number 272 and 296 (amino acids 91 to 99) coincide with the region of the conformational epitope.…”

“…No BLV strain was found, in which antigenes F, G and H were absent at the same time. This implies that these epitopes are connected with viral infectivity (Moratorio et al, 2013). Rabbit antibodies against peptides 9-48, 78-92, 144-157 and 177-192 neutralize VSV/BLV pseudotypes in vitro, which is also a sign of their connection with viral infectivity (Johnston et al, 2002).…”

Genetic variability and phylogeny of the 5' long terminal repeat from Brazilian bovine leukemia virus

“…This is considered to be a highly conserved region with few nucleotide substitutions even in viruses isolated from different cell types such as peripheral blood mononuclear cells, tumor cells, experimentally infected sheep, and cell lines (FLK) or B-cell lymphosarcomas (Moratorio et al, 2013). Merezak et al (2001) demonstrated that minor variations in the cyclic AMP-responsive elements result in negative transcription regulation of BLV and may contribute to viral escape from the immune system and establishment of persistent infection.…”

“…Zhao et al (2007) found significant variability in studied sequences of the 5'LTR from BLV strains from North America, Costa Rica, Japan, and Belgium, identifying 7 genetic groups and demonstrating that the transcriptional regulation region can be analyzed in phylogenetic studies of the virus. Furthermore, LTR region variability may contribute to viral transcription regulation, a process that is directly related to BLV virulence and pathogeny (Moratorio et al, 2013). In addition, small nucleotides polymorphisms identified in the LTR region may be responsible for the emergence of the 2 different infection profiles (Juliarena et al, 2013).…”