Mapping of B-neutralizing and T-helper cell epitopes on the bovine leukemia virus external glycoprotein gp51

Callebaut, Isabelle; Voneche, V.; Mager, A.; Fumière, Olivier; Krchňák, Viktor; Mérza, M.; Závada, Jan; Mammerickx, Marc; Burny, Arsène; Portetelle, Daniel

doi:10.1128/jvi.67.9.5321-5327.1993

Cited by 69 publications

(49 citation statements)

References 27 publications

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“…The N‐terminal half of BLV gp51 protein contains three conformational epitopes, F, G and H, important for viral infectivity and syncytium formation (Bruck et al., ; Portetelle et al., ), while the C‐terminal half contains the linear epitopes, A, B, D and E (Bruck et al., ). In addition, three neutralization domains (ND1, ND2 and ND3) are located in gp51 (Callebaut et al., ). Deduced amino acid sequence analysis in this work revealed that amino acid substitutions in Indian BLV strains were found mostly in known epitopes of gp51, epitope G, ND2 and epitope D rather than at random locations in consistent with previous studies (Polat, Takeshima et al., ; Zhao & Buehring, ).…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Bovine Leukaemia Virus (BLV) Strains Reveals Existence of Genotype 6 in Cattle in India with evidence of a new subgenotype

Gautam

Mishra

Kalaiyarasu

et al. 2018

Transbound Emerg Dis

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Bovine leukaemia virus (BLV) causes enzootic leucosis in cattle and is prevalent worldwide. Although recent studies have shown that BLV strains can be classified into 10 distinct genotypes, no information is available regarding the BLV genotype prevalent in cattle in India. To determine the genetic variability in BLV, in this study, 118 adult dairy cows from three states of India were screened for BLV infection by env gp51-specific ELISA and nested PCR. Of the 33 cows found positive by both PCR and ELISA, 10 selected BLV strains were subjected to molecular characterization. Phylogenetic analyses of partial and full-length env gp51 gene sequences of Indian BLV strains and other geographical diverse BLV strains representing all the 10 genotypes revealed that Indian strains belonged to BLV genotype 6. Although Indian strains showed close genetic proximity with the strains circulating in South America, they were classified into a new subgenotype within genotype 6. Alignment of deduced amino acid sequences in gp51 demonstrated substitutions mainly in conformational epitope G, neutralizing domain 2 and linear epitope D, with a novel mutation (threonine to alanine at residue 252) found in D-epitope of all the Indian BLV strains. Although serological evidence of BLV infection in India has been reported earlier, this study on molecular characterization of BLV strains established the existence of BLV genotype 6 in India. Additionally, the results of this study highlight the importance of genetic analysis of geographically diverse BLV strains to understand BLV global genetic diversity and further studies are required to determine BLV genetic diversity and extent of BLV infection in cattle in India.

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Bovine Leukaemia Virus (BLV) Strains Reveals Existence of Genotype 6 in Cattle in India with evidence of a new subgenotype

Gautam

Mishra

Kalaiyarasu

et al. 2018

Transbound Emerg Dis

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“…Expression of the BLV epitopes in the carboxy terminus of BTV-10 NS1. The various biological functions of the external glycoprotein, gp51, of BLV have recently been mapped by using synthetic peptides (2). In an attempt to insert a foreign peptide in NS1, three different epitopes of BLV were selected.…”

Section: 5ј-ctagtaacagtgactgggttccctctgtcagatcatgggccctg-3јmentioning

confidence: 99%

“…A second sequence representing amino acids 155 to 167 of BLV gp51 was selected for addition to the C terminus of NS1. This sequence is believed to be involved in binding to cellular receptors (2). The recombinant AcNS1eBLp4 was derived and used to express the chimeric NS1.…”

Section: 5ј-ctagtaacagtgactgggttccctctgtcagatcatgggccctg-3јmentioning

confidence: 99%

Characterization and modification of the carboxy-terminal sequences of bluetongue virus type 10 NS1 protein in relation to tubule formation and location of an antigenic epitope in the vicinity of the carboxy terminus of the protein

Monastyrskaya

Gould

Roy

1995

J Virol

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Bluetongue virus produces large numbers of tubules during infection. The tubules are formed from a 552-amino-acid, 64-kDa NS1 protein encoded by the viral double-stranded RNA segment M6. A series of deletion and extension mutants of bluetongue virus serotype 10 NS1 has been generated and expressed in insect cells in order to identify the carboxy-terminal components of the protein which are important for tubule formation. The mutants AcCT5 and AcCT10, lacking 5 and 10 of the carboxy-terminal residues, respectively, were prepared. By analyzing their abilities to form tubules, it was shown that AcCT5 was capable of this function whereas AcCT10 was not, indicating that the last five amino acids are not strongly involved in NS1 tubule formation. Extension mutants including foreign antigenic sequences involving up to 16 amino acids added to the C terminus of NS1 were shown to form tubules, although an extension of 19 amino acids inhibited tubule formation. Analysis of a panel of monoclonal antibodies has established that an NS1 antigenic site is located near the carboxy terminus of the protein. It appears to be exposed on the surface of tubules. The opportunities to develop new vaccines using recombinant NS1 to deliver foreign epitopes are discussed.

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“…Lymphocyte proliferation to MBP and MBP-LacZ was low and used as control (background) proliferation in experiments with recombinant proteins. As in other studies (7,13,14), antigen-specific proliferation was considered positive if the stimulation index (SI; defined as mean counts of test sample divided by mean counts of control) was greater than 2.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, CD4 ϩ T-cell epitopes were identified on gp51 by using lymphocytes from BLV-negative cattle and sheep (13) and vaccinia virusvaccinated sheep (14); however, lymphocytes from BLV-infected animals failed to produce specific responses. Nevertheless, B-cell depletion helped reduce background proliferation, and several CD4 ϩ determinants on gp51 (7) and p24 (31) recognized by lymphocytes from infected cattle were identified. Unfortunately, animals in the PL stage still could not be evaluated because of high spontaneous proliferation.…”

mentioning

confidence: 99%

Progression to persistent lymphocytosis and tumor development in bovine leukemia virus (BLV)-infected cattle correlates with impaired proliferation of CD4+ T cells in response to gag- and env-encoded BLV proteins

Orlik

Splitter

1996

J Virol

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The mechanism of leukemogenesis and persistent lymphocytosis (PL; benign expansion of B lymphocytes) in cattle infected with bovine leukemia virus (BLV; a retrovirus closely related to human T-cell leukemia virus type 1) is unknown; however, the immune system likely plays an important role in controlling the outcome of infection. In this study, we compared T-cell competence in serologically positive alymphocytotic (AL) animals with T-cell functions in animals with progressive stages of infection, PL and tumor bearing (TB). Dramaticdifferences were observed in lymphocyte proliferation to recombinant proteins encoded by BLV gag (p12, p15, and p24) and env (gp30, and gp51) genes in different disease stages. Lymphocytes from AL cattle recognized an average of three of five recombinant proteins per animal. Expansion of antigen pulsed lymphocytes in interleukin-2 increased protein recognition to almost five per animal. In contrast, lymphocytes from PL and TB animals failed to recognize any BLV recombinant proteins. Short-term T-cell cultures from the PL group expanded in interleukin-2, as well as the PL and TB cells cultured in indomethacin (3 to 6 g/ml), increased the average of recognized proteins per animal to one. Cells proliferating to BLV antigens were CD4 ؉ T lymphocytes, as shown by cell depletion studies. The positive effect of indomethacin suggests involvement of prostaglandin E 2 as a negative regulatory factor in the later stages of disease. Thus, for the first time, advancing stages of BLV infection were correlated with decreased T-cell competence, providing deeper insight into pathogenesis of retroviral infections.

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Mapping of B-neutralizing and T-helper cell epitopes on the bovine leukemia virus external glycoprotein gp51

Cited by 69 publications

References 27 publications

Molecular Characterization of Bovine Leukaemia Virus (BLV) Strains Reveals Existence of Genotype 6 in Cattle in India with evidence of a new subgenotype

Molecular Characterization of Bovine Leukaemia Virus (BLV) Strains Reveals Existence of Genotype 6 in Cattle in India with evidence of a new subgenotype

Characterization and modification of the carboxy-terminal sequences of bluetongue virus type 10 NS1 protein in relation to tubule formation and location of an antigenic epitope in the vicinity of the carboxy terminus of the protein

Progression to persistent lymphocytosis and tumor development in bovine leukemia virus (BLV)-infected cattle correlates with impaired proliferation of CD4+ T cells in response to gag- and env-encoded BLV proteins

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