Monoclonal antibodies define eight independent antigenic regions on the bovine leukemia virus (BLV) envelope glycoprotein gp51

Bruck, Claudine; Mathot, Sylvie; Portetelle, Daniel; Berte, Christine; Franssen, Jean-Denis; Hérión, Pascal; Burny, Arsène

doi:10.1016/0042-6822(82)90234-3

Cited by 108 publications

(50 citation statements)

References 12 publications

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“…Interestingly, the majority of amino acid substitutions in the SU glycoprotein were located at known antigenic determinants ( Fig. 1) (Ban et al, 1992;Bruck et al, 1982aBruck et al, , b, 1984aCallebaut et al, 1991Callebaut et al, , 1993Gatei et al, 1993;Portetelle et al, 1989). This uneven distribution of non-synonymous variability strongly suggests that mutation at these positions of the env gene could be driven by the host immune response.…”

Section: Resultsmentioning

confidence: 99%

Bovine leukemia virus can be classified into seven genotypes: evidence for the existence of two novel clades

Rodríguez¹,

Golemba²,

Campos³

et al. 2009

Journal of General Virology

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Previous studies have classified the env sequences of bovine leukemia virus (BLV) provirus from different locations worldwide into between two and four genetic groupings. These different studies gave unique names to the identified groups and no study has yet integrated all the available sequences. Thus, we hypothesized that many of the different groups previously identified actually correspond to a limited group of genotypes that are unevenly distributed worldwide. To examine this hypothesis, we sequenced the env gene from 28 BLV field strains and compared these sequences to 46 env sequences that represent all the genetic groupings already identified. By using phylogenetic analyses, we recovered six clades, or genotypes, that we have called genotypes 1, 2, 3, 4, 5 and 6. Genotypes 1-5 have counterparts among the sequence groupings identified previously. One env sequence did not cluster with any of the others and was highly divergent when compared with the six genotypes identified here. Thus, an extra genotype, which we named 7, may exist. Similarity comparisons were highly congruent with phylogenetic analyses. Furthermore, our analyses confirmed the existence of geographical clusters. INTRODUCTIONBovine leukemia virus (BLV) is a member of the family Retroviridae belonging to the genus Deltaretrovirus. This genus also includes Simian T-lymphotropic virus 1, 2, 3 and 5 (STLV-1, -2, -3 and -5) and Human T-lymphotropic virus 1, 2, 3 and 4 (HTLV-1, -2, -3 and -4). have not yet been associated with any pathology, likely due to their recent identification and to the low number of isolates. Therefore, BLV is considered a model of HTLV-1 and -2 . BLV is recognized as the aetiological agent of enzootic bovine leukosis, a disease that results in significant economic losses for the worldwide cattle industry. The most conspicuous clinical manifestation of bovine leukosis, which only develops in a small fraction of infected animals, is the clonal expansion and local accumulation of B cells that results in the development of lymphoid tumours (lymphosarcoma, LS) (Gillet et al., 2007). The majority of infections are not associated with any clinical signs (AL), and in approximately 30 % of infected cattle, the virus causes a persistent lymphocytosis (PL) (Burny et al., 1987;Mirsky et al., 1996).Analyses of the BLV envelope (env) gene of isolates collected in multiple geographical locations demonstrated significant sequence conservation (Camargos et al., 2002(Camargos et al., , 2007Coulston et al., 1990). Nevertheless, up to seven BLV genotypes can be identified by RFLP analysis (Asfaw et al., 2005;Coulston et al., 1990;Fechner et al., 1997;Kettmann et al., 1981;Licursi et al., 2002). Furthermore, the env sequences of the BLV provirus from different locations worldwide have previously been classified into between two and four genetic groupings (Camargos et al., 2002(Camargos et al., , 2007Felmer et al., 2005;Hemmatzadeh, 2007;Licursi et al., 2003;Mamoun et al., 1990;Monti et al., 2005;Zhao & Buehring, 2007), with similar results...

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Section: Resultsmentioning

confidence: 99%

Bovine leukemia virus can be classified into seven genotypes: evidence for the existence of two novel clades

Rodríguez¹,

Golemba²,

Campos³

et al. 2009

Journal of General Virology

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“…There are two forms of such cooperativity: first where binding of an antibody synergistically increases binding by antibody to a different epitope and second where there is enhanced neutralization without increased binding of antibody. Synergistic binding of monoclonal antibodies has been detected in competition binding assays with influenza virus (Lubeck & Gerhard, 1982), vesicular stomatitis virus (VSV) (Lefrancois & Lyles, 1982), La Crosse virus (Kingsford et al, 1983), bovine leukaemia virus (Bruck et al, 1982) and Sindbis virus (Clegg et al, 1983). Such synergism has been associated with increased neutralization with La Crosse virus (Kingsford & Ishizawa, 1984;L.…”

Section: Cooperative Neutralizationmentioning

confidence: 99%

Mechanisms of Neutralization of Animal Viruses

Dimmock

1984

Journal of General Virology

130

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“…The putative P-rich region of BLV SU is followed by the C terminus containing the epitopes A, B, D, and most of E (5,8). These epitopes are classified as linear because they were mapped with peptides (2,8).…”

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confidence: 99%

Envelope Proteins Containing Single Amino Acid Substitutions Support a Structural Model of the Receptor-Binding Domain of Bovine Leukemia Virus Surface Protein

Johnston

Albritton

Radke

2002

J Virol

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Functional domains of the strikingly conserved envelope (Env) glycoproteins of bovine leukemia virus (BLV) and its close relative, human T-cell leukemia virus type 1 (HTLV-1), are still being defined. We have used BLV Env protein variants to gain insights into the structure and function of this important determinant of viral infectivity. Each of 23 different single amino acid variants found in cDNA clones of env transcripts present after short-term culture of peripheral blood mononuclear cells from BLV-infected sheep was expressed in COS-1 cells and tested for the ability to mediate cell fusion and to be cleaved to surface (SU) and transmembrane (TM) protein subunits. Of 11 Env variants that failed to induce syncytia or did so poorly, 7 contained changes in amino acids identical or chemically conserved in the HTLV-1 Env protein. These seven included the four variants that showed aberrant proteolytic cleavage and poor cell surface expression, underscoring their importance for Env structure. Ten of 12 variants that retained wild-type syncytium-inducing ability clustered in the N-terminal half of BLV SU, which forms the putative receptor-binding domain (RBD). Several variants in the RBD showed evidence of subtle misfolding, as judged by reduced binding to monoclonal antibodies recognizing conformational epitopes F, G, and H formed by the N terminus of SU. We modeled the BLV RBD by aligning putative structural elements with known elements of the ecotropic Friend murine leukemia virus RBD monomer. All the variant RBD residues but one are exposed on the surface of this BLV model. These variants as well as function-altering, antibody-reactive residues defined by other investigators group on one face of the molecular model. They are strikingly absent from the opposite face, implying that it is likely to face inward in Env complexes. This surface might interact with the C-terminal domain of SU or with an adjacent monomer in the Env oligomer. This location suggests an orientation for the monomer of ecotropic Friend murine leukemia virus RBD.Envelope (Env) proteins confer infectivity on retroviral particles. Oligomers of these proteins bind to receptors on the surfaces of host cells and mediate entry of the viral genome into the cell. The Env protein complex is composed of surface glycoprotein (SU) subunits, which are anchored to virions by their association with transmembrane (TM) protein subunits. SU molecules recognize and bind to cellular receptors, thereby initiating a complex series of conformational changes that lead to fusion of viral and cellular membranes by TM oligomers (reviewed in reference 30). Upon successful synthesis of the DNA provirus and its integration into host cell DNA, expression of viral genes ensues. When the newly synthesized polyprotein Env precursor is cleaved in the Golgi apparatus of the virus-producing host cell, SU and TM subunits remain associated in a metastable state (18). Oligomers of mature Env proteins are transported to the cell surface membrane, where they can be incorporated into b...

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Monoclonal antibodies define eight independent antigenic regions on the bovine leukemia virus (BLV) envelope glycoprotein gp51

Cited by 108 publications

References 12 publications

Bovine leukemia virus can be classified into seven genotypes: evidence for the existence of two novel clades

Bovine leukemia virus can be classified into seven genotypes: evidence for the existence of two novel clades

Mechanisms of Neutralization of Animal Viruses

Envelope Proteins Containing Single Amino Acid Substitutions Support a Structural Model of the Receptor-Binding Domain of Bovine Leukemia Virus Surface Protein

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