Natural genetic variations in bovine leukemia virus envelope gene: Possible effects of selection and escape

Abstract

Bovine leukemia virus (BLV) is an oncogenic virus widespread in cattle. It belongs to the genus Deltaretrovirus of the family Retroviridae along with human and simian T-lymphotropic viruses. Here we report the addition of 28 new sequences to the current literature of 16 full-length BLV envelope gene sequences. The phylogenetic clustering, genotyping, and geographic distribution of BLV env variations corresponded in most cases. Most natural variations are mapped to the surface of the proposed conformational models of BLV gp51 N-terminus and gp30 external domain, overlapping with or adjacent to immunogenic epitopes. Analyses for evidence of possible selection pressures suggest the BLV env is under stringent negative selection overall, while strong positive selection is indicated for immunogenic epitope G. Natural env deletions bounded by similar flanking sequences were observed in multiple isolates and would result in truncated signal peptides, missing gp51, and aberrant coding frames for other proteins.

Genetic variation of bovine leukemia virus (BLV) after replication in cell culture and experimental animals

“…In the past, the BLV env gene mutation rate was assumed to be low, even after the experimental passage of the provirus in vivo (Juliarena et al, 2013). Even though BLV has been shown to have lower genetic variation compared to other retroviruses (Price et al, 1998;Craigo et al, 2009), and to contain highly conserved regions involved in the cell-virus interaction (Coulston et al, 1990;Mamoun et al, 1990), our results support recent studies reporting about the genetic variation of BLV and the circulation of 7 genetic distinct groups (Zhao and Buehring, 2007;Moratorio et al, 2010), of which 4 were detected in Brazil (Camargos et al, 2002(Camargos et al, , 2007.…”

“…This homology might be the result of the selection of mutants that might be predecessors of the Brazil 1 and 3 variants in the infected leucocytes of cow 141. It has been suggested that env proviral sequences from different locations might be classified into groups (Camargos et al, 2002;Zhao and Buehring, 2007). Furthermore, the presence of BLV different groups in one geographical area has been reported before (Camargos et al, 2007;Zhao and Buehring, 2007;Moratorio et al, 2010), which might explain how different strains possibly infected the cows studied.…”

“…In contrast to that observed for other retroviruses, including Human Immunodeficiency virus (HIV) (Price et al, 1998) and equine infectious anemia (EIAV) (Craigo et al, 2009), the BLV envelope gene exhibits low levels of variation (Mamoun et al, 1990;Willems et al, 1995), because BLV env gene sequence substitutions are usually silent (Dube et al, 2000;Camargos et al, 2002). However, recent studies have indicated the circulation of 7 different BLV genotypes that might be associated with the geographic origin of the isolates, contradicting previous assumptions (Camargos et al, 2007;Zhao and Buehring, 2007;Moratorio et al, 2010).…”

Bovine Leukemia Virus Gene Segment Detected in Human Breast Tissue

“…Meanwhile, Michael Bock and Jonathan P. Stoye (2000), demonstrated endogenous retroviruses in germinal human cells genome and the possible association of them with the development of some cancers by the mutation done by the insertion of the viral genome in the human cells [18]. For the year 2003 Buering et al, reported antibodies against p24 protein of BLV in 74% of human sera [19] and in the same year, Jehoon Lee and coworkers presented an article in which they did not find BLV in leukemia nor human lymphomas even though it was argued that food workers, especially with meat, have a higher risk of developing a myeloid leukemia, Hodgkin's lymphoma or lung cancer [20].…”

“…From these animals, 5% of them develops a leukemia or a lymphoma [6,7]. Besides of infecting cattle, some other authors have proposed the possibility of transmission to other species, including humans [8].…”