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| Serological responses in cats vaccinated with FeLV ISCOM and an inactivated FeLV vaccine. (1989) | |||||||||
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| Various approaches have been considered for generation of effective and safe vaccines against retroviruses, including HIV, with limited success. In the present vaccination study, encompassing 137 household cats, we have composed an experimental ISCOM subunit vaccine containing gp70 of feline leukaemia virus (FeLV)--the external glycosylated envelope protein, and the transmembrane protein p15E, with a commercial available inactivated FeLV vaccine (Leukocell). The two vaccines were estimated to contain approximately the same amount of gp70 antigen and the cats were immunized three times according to the recommendations of the commercial vaccine. A control preparation not containing gp70 or p15E was also included. During the observation period of 200 days all cats remained healthy and no virus was isolated during the isolation attempts. The serological responses were measured in ELISA, membrane immunofluorescence (MIF) and virus neutralization (VN) tests. In contrast to the cats in the other groups almost all ISCOM-vaccinated cats responded by seroconversion or increased titres in the three tests. The development of specific antibodies to gp70 and p15E were confirmed in Western blot. These results clearly illustrate the potential of the ISCOM structure for the development of safe and effective vaccines against retroviruses. | |||||||||
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| Induction of feline leukemia virus neutralizing antibodies by immunization with synthetic peptides derived from the FeLV env gene. (1993) | |||||||||
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| The surface glycoprotein, gp70, of feline leukaemia virus (FeLV) contains sites which are important in inducing neutralizing antibodies. Using synthetic peptides corresponding to nucleotide sequence 729-957 (amino acid sequence 243-319) of FeLV-A/Glasgow-1, the antigenicity and immunogenicity of this part of the viral surface glycoprotein were investigated. The region contains two highly conserved domains separated by a variable region (VR4), when compared with FeLV of subgroups B and C, and an epitope known to be involved in virus neutralization is located in the N-terminal conserved domain. Five murine monoclonal antibodies generated by immunization with virus were found to be directed to this domain and four were virus-neutralizing. Polyclonal mouse, rabbit and cat anti-FeLV antisera, which were virus-neutralizing, were directed to B-cell epitopes in the peptides. To determine if those synthetic peptides could induce neutralizing antibodies, rabbits were immunized with the peptides, singly or in combination. Antibody responses were measured by ELISA for anti-peptide, anti-FeLV and anti-gp70 activity, by immunoblotting, by membrane immunofluorescence and by virus-neutralization tests. Virus-neutralizing antibodies were induced by FeLV gp70 peptides and there was a synergistic effect on antibody production when a combination of peptides covering amino acid sequence 243-319 of FeLV-A was used. In a second experiment, six rabbits and six cats were immunized with a combination of two peptides, which covered the above-defined FeLV gp70 sequence. Comparisons were made of the responses to these peptides incorporated into immunostimulating complexes (ISCOMs) via myristic acid tails, inoculated with 'empty' ISCOMs, or with Al(OH)3. Complete Freund's adjuvant (CFA) had a very strong potentiating effect on the induction of antibodies and immunization with peptides incorporated into ISCOMs was superior to immunization using adjuvants other than CFA. It is very promising that not only in rabbits, but also in the natural host of FeLV, the cat, anti-FeLV gp70 (peptides) antibodies could be induced by FeLV gp70 peptides. | |||||||||
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| Lymphocyte subset alterations and viral determinants of immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS. | |||||||||||
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| The FeLV-FAIDS strain of feline leukemia virus consistently induces fatal immunodeficiency. To investigate the immunopathogenesis and viral genetic determinants responsible for the induction of immunodeficiency disease in vivo, we have generated chimeras between the two major viral genomes in the original virus isolate, designated common form clone 61E and major variant clone 61C, which were molecularly cloned directly from DNA of the same animal and tissue. Each of three 61E/C chimeras, containing at minimum a 34-amino-acid segment (including a 6-amino-acid insertion and one amino acid substitution) near the C terminus of the 61C surface glycoprotein (gp70), induced fatal immunodeficiency disease in all (12 of 12) infected animals over a course of 33 +/- 10 weeks. By contrast, animals infected with virus 61E, although persistently antigenemic, remained asymptomatic throughout a 48-week observation period. Beginning 14 weeks after infection, a significant decrease (8 to 10%) in the percent of circulating CD4+ T lymphocytes developed in the 61E/C chimera-infected cats, compared with either 61E-infected or control animals. At this time, no significant changes were seen in CD8 cells, B cells, or mitogen-induced blastogenesis. Prior to this initial decline in CD4 cells, the ability of all antigenemic 61E/C-infected cats to generate a primary antibody response to the T-cell-dependent antigen keyhole limpet hemocyanin was markedly impaired, whereas all 61E-infected cats, one 61E/C-infected but nonviremic cat, and all uninfected control cats produced normal antibody responses. The results reported here demonstrate that a major determinant of in vivo immunodeficiency induction by FeLV-FAIDS is contained within a 34-amino-acid C-terminal segment of its surface glycoprotein and that this gp70 alteration determines the early and persistent deficits in CD4+ T lymphocytes and T-cell-dependent antibody responses. We hypothesize that these early immunologic alterations could result from early deletion of a CD4+ helper T-cell subset. | |||||||||||
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http://en.scientificcommons.org/11598594
| Differential Pathogenicity of Two Feline Leukemia Virus Subgroup A Molecular Clones, pFRA and pF6A | |||||||||||||
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| F6A, a molecular clone of subgroup A feline leukemia virus (FeLV) is considered to be highly infectious but weakly pathogenic. In recent studies with a closely related subgroup A molecular clone, FRA, we demonstrated high pathogenicity and a strong propensity to undergo recombination with endogenous FeLV (enFeLV), leading to a high frequency of transition from subgroup A to A/B. The present study was undertaken to identify mechanisms of FeLV pathogenesis that might become evident by comparing the two closely related molecular clones. F6A was shown to have an infectivity similar to that of FRA when delivered as a provirus. Virus load and antibody responses were also similar, although F6A-infected cats consistently carried higher virus loads than FRA-infected cats. However, F6A-infected cats were slower to undergo de novo recombination with enFeLV and showed slower progression to disease than FRA-infected cats. Tumors collected from nine pF6A- or pFRA-inoculated cats expressed lymphocyte markers for T cells (seven tumors) and B cells (one tumor), and non-T/B cells (one tumor). One cat with an A-to-A/C conversion developed erythrocyte hypoplasia. Genomic mapping of recombinants from pF6A- and pFRA-inoculated cats revealed similar crossover sites, suggesting that the genomic makeup of the recombinants did not contribute to increased progression to neoplastic disease. From these studies, the mechanism most likely to account for the pathologic differences between F6A and FRA is the lower propensity for F6A to undergo de novo recombination with enFeLV in vivo. A lower recombination rate is predicted to slow the transition from subgroup A to A/B and slow the progression to disease. | |||||||||||||
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A Novel Truncated env Gene Isolated from a Feline Leukemia Virus-Induced Thymic
Lymphosarcoma
http://en.scientificcommons.org/11598001
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| We PCR amplified the exogenous feline leukemia virus (FeLV)-related env gene species from lymphosarcomas induced by intradermally administered plasmid DNA of either the prototype FeLV, subgroup A molecular clone, F6A, or a new molecular clone, FeLV-A, Rickard strain (FRA). Of the nine tumors examined, six showed the presence of deleted env species of variable sizes in the tumor DNA. One env mutant, which was detected in a FRA-induced thymic lymphosarcoma, had a large internal deletion beginning from almost the N-terminal surface glycoprotein (SU) up to the middle region of the transmembrane (TM) protein of the env gene. The deduced polypeptide of this truncated env (tenv) retained the complete signal peptide and seven amino acids of the N-terminal mature SU of FRA env gene, followed by eight amino acids from the frameshift in the TM region. To study the biological function of tenv, we used a murine retrovirus vector to produce amphotropic virions. Infection of feline fibroblasts (H927), human fibrosarcoma cells (HT1080), or human B-lymphoma cells (Raji) led to pronounced cytotoxicity, while the tenv virus did not induce significant cytotoxicity to feline T-lymphoma cells (3201B) or human T-lymphoma cells (CEM). Together, these results convincingly demonstrated that the genetic events that led to truncation in the env gene occurred de novo in FeLV lymphomagenesis and that such a product, tenv could induce cytotoxicity to fibroblastic and B-lymphoid cells but not to T-lymphoid tumor cells. This type of selective toxicity might be potentially important in the development of the neoplastic disease. | |||||||||||||
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Ghosh, Sajal K., Roy-Burman, Pradip, Faller, Douglas V.
We have previously reported that the long terminal repeat (LTR) region of feline leukemia viruses (FeLVs) can enhance expression of certain cellular genes such as the collagenase IV gene and MCP-1 in...
Chang, Zongli, Pan, Judong, Logg, Christopher, Kasahara, Noriyuki, Roy-Burman, Pradip
We previously established that lymphoid tumors could be induced in cats by intradermal injection of ecotropic feline leukemia virus (FeLV), subgroup A, plasmid DNA. In preparation for in vivo...
Pathogenicity Induced by Feline Leukemia Virus, Rickard Strain, Subgroup A Plasmid DNA (pFRA)
Chen, Hang, Bechtel, Marta K., Shi, Yan, Phipps, Andrew, Mathes, Lawrence E., Hayes, Kathleen A., ...
A new provirus clone of feline leukemia virus (FeLV), which we named FeLV-A (Rickard) or FRA, was characterized with respect to viral interference group, host range, complete genome sequence, and in...
Horzinek, M.C. Hartmann, K. Donath, A. Beer, B. Egberink, H.F. Lutz, H. Hoffmann-Fezer, G. Thum, I. Thefeld, S.
Weijer, K. Pfauth, A. Van Herwijnen, R. Jarrett, O. Meloen, R.H. Tomee, C. Osterhaus, A.D.M.E.
glycoprotein, gp70, of feline leukaemia virus (FeLV) contains sites which are important in inducing neutralizing antibodies. Using synthetic...
Lymphocyte subset alterations and viral determinants of immunodeficiency disease
induction by the...
Quackenbush, S L Donahue, P R Dean, G A Myles, M H Ackley, C D Cooper, M D Mullins, J I Hoover, E A
The FeLV-FAIDS strain of feline leukemia virus consistently induces fatal immunodeficiency. To investigate the immunopathogenesis and viral genetic...
Characterization and significance of delayed processing of the feline leukemia virus FeLV-FAIDS...
Poss, M L Quackenbush, S L Mullins, J I Hoover, E A
FeLV-FAIDS, an immunodeficiency-inducing isolate of feline leukemia virus, is composed of a pathogenic but replication-defective genome (molecular...
Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline...
Donahue, P R Quackenbush, S L Gallo, M V deNoronha, C M Overbaugh, J Hoover, E A Mullins, J I
strain of feline leukemia virus, FeLV-FAIDS, are viruses which range in pathogenicity from minimally (clone 61E is the prototype) to...
Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline...
Donahue, P R Quackenbush, S L Gallo, M V deNoronha, C M Overbaugh, J Hoover, E A Mullins, J I
strain of feline leukemia virus, FeLV-FAIDS, are viruses which range in pathogenicity from minimally (clone 61E is the prototype) to...
Reinhart, Todd A. Harvard School of Public Health.
Thesis (Doctor of Science)--Harvard School of Public Health, 1992. Includes bibliographical references.
Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline...
Donahue, P R Quackenbush, S L Gallo, M V deNoronha, C M Overbaugh, J Hoover, E A Mullins, J I
strain of feline leukemia virus, FeLV-FAIDS, are viruses which range in pathogenicity from minimally (clone 61E is the prototype) to...
Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline...
Donahue, P R Quackenbush, S L Gallo, M V deNoronha, C M Overbaugh, J Hoover, E A Mullins, J I
strain of feline leukemia virus, FeLV-FAIDS, are viruses which range in pathogenicity from minimally (clone 61E is the prototype) to...
Reinhart, Todd A. Harvard School of Public Health.
Thesis (Doctor of Science)--Harvard School of Public Health, 1992. Includes bibliographical references.
Modulation of the immune response towards anti-FeLV immunity with anti- idiotype antibodies. (1988)
Weijer, K. UytdeHaag, F.G.C.M. Osterhaus, A.D.M.E.
Formation and characterization of FeLV iscoms. (1989)
Akerblom, L. Strömstedt, K. Höglund, S. Osterhaus, A.D.M.E. Morein, B.
have been prepared from feline leukaemia virus (FeLV) envelope proteins. The ISCOMs were characterized biochemically in SDS-polyacrylamide gel...
Insertional mutagenesis of flvi-2 in tumors induced by infection with LC-FeLV, a myc-containing...
Levy, L S Lobelle-Rich, P A
LC-FeLV is a myc-containing strain of feline leukemia virus (FeLV) which exhibits only partial transforming activity in vitro and in vivo. LC-FeLV...
Insertional mutagenesis of flvi-2 in tumors induced by infection with LC-FeLV, a myc-containing...
Levy, L S Lobelle-Rich, P A
LC-FeLV is a myc-containing strain of feline leukemia virus (FeLV) which exhibits only partial transforming activity in vitro and in vivo. LC-FeLV...
Osterhaus, A.D.M.E. Weijer, K. UytdeHaag, F. Knell, P. Akerblom, L. Morein, B.
A Replication-Competent Feline Leukemia Virus, Subgroup A (FeLV-A), Tagged with Green Fluorescent...
Chang, Zongli Pan, Judong Logg, Christopher Kasahara, Noriyuki Roy-Burman, Pradip
injection of ecotropic feline leukemia virus (FeLV), subgroup A, plasmid DNA. In preparation for in vivo experiments to study the cell-to-cell...
A Replication-Competent Feline Leukemia Virus, Subgroup A (FeLV-A), Tagged with Green Fluorescent...
Chang, Zongli Pan, Judong Logg, Christopher Kasahara, Noriyuki Roy-Burman, Pradip
injection of ecotropic feline leukemia virus (FeLV), subgroup A, plasmid DNA. In preparation for in vivo experiments to study the cell-to-cell...
Antibodies neutralizing feline leukaemia virus (FeLV) in cats immunized with the transmembrane...
Langhammer, Stefan Hübner, Janine Kurth, Reinhard Denner, Joachim
The feline leukaemia virus (FeLV) vaccines that are currently in wide use are generally poor inducers of virus-neutralizing antibodies, although such...
Jackson, Marion Louise
The feline leukemia virus (FeLV) causes degenerative and proliferative hemolymphatic diseases in domestic cats. Some cats with clinicopathologic...
Regulation of FeLV-945 by c-Myb binding and CBP recruitment to the LTR (2004)
Finstad, Samantha L Prabhu, Sudha Rulli, Karen R Levy, Laura S
Abstract Background Feline leukemia virus (FeLV) induces degenerative, proliferative and malignant hematologic disorders in its natural host, the...
Dynamics of a feline retrovirus (FeLV) in host populations with variable spatial structure.
Fromont, E Pontier, D Langlais, M
models of Feline Leukaemia Virus (FeLV). We use two different incidence terms, i.e. proportionate mixing and pseudo-mass action....