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O Jarrett

Publications and source records attributed to O Jarrett.

At least 73 records · Page 4Linked to original sources
PubMed1994

Virus neutralization reveals antigenic variation among feline immunodeficiency virus isolates.

By using a focus reduction assay in CrFK feline fibroblast cells, virus neutralizing antibodies (VNA) to feline immunodeficiency virus (FIV) were demonstrated in cats that had been naturally or experimentally infected with FIV. The antigenic relatedness of four strains of FIV, divergent in nucleotide sequence within the env gene, was investigated by neutralization following adaptation of each virus for growth in CrFK cells. Two of the viruses were from The Netherlands (FIV/AM-4 and AM-6), one was from the U.K. (FIV/GL-8) and one was from the U.S.A. (FIV/PET). Reaction of the viruses in the neutralization assay with cat antibodies to homologous or heterologous strains indicated that while there was a degree of cross-reactivity between all four, there were consistent differences suggesting the existence of FIV neutralization subtypes. In particular, FIV/PET and FIV/AM-6 were closely related but FIV/PET and FIV/GL-8 were clearly distinct. VNA from naturally infected cats in the field showed a pattern of reactivity against FIV/PET and FIV/GL-8 that confirmed the antigenic diversity of FIV.

Animals↗
PubMed1994

Polyclonal B-cell activation in cats infected with feline immunodeficiency virus.

The specificity of the antibody response following natural or experimental infection of domestic cats with feline immunodeficiency virus (FIV) was examined. The antibody response to a range of non-viral antigens, including trinitrophenol (TNP), ovalbumin, beta-galactosidase, deoxyribonucleic acid (DNA) and keyhole limpet haemocyanin (KLH), was measured in 220 cats naturally infected with FIV. Infected cats had higher antibody levels to these antigens, in particular TNP, KLH and beta-galactosidase, than non-infected control cats. Competition binding studies demonstrated that this response was not due to the presence of cross-reacting epitopes on recombinant FIV p17 or p24 antigens, suggesting that the B-cell activation associated with infection was polyclonal rather than entirely virus specific. Studies on cats experimentally infected with FIV revealed a similar pattern, with infected cats developing an antibody response to heterologous non-viral antigens at 6-8 weeks post-infection. There were two discernible peaks of antibody activity, the first occurring 10-20 weeks post-infection and the second peak 40-60 weeks post-infection. The antibody response to KLH, DNA and beta-galactosidase remained elevated throughout the 90-week study period, whereas the antibody levels to the other antigens declined to levels approaching those observed in normal cats.

Animals↗
PubMed1994

Identification of a putative cellular receptor for feline immunodeficiency virus as the feline homologue of CD9.

A monoclonal antibody vpg15 has been identified which recognizes a putative cellular receptor for feline immunodeficiency virus (FIV). The antibody immunoprecipitates a single 24,000 MW species from feline cells. The molecular size and pattern of expression of the ligand for the vpg15 antibody displayed similarities to that of the human leucocyte differentiation antigen CD9. The reactivity of the vpg15 antibody was therefore compared with that of the anti-human CD9 antibody FMC56, an antibody which cross-reacts with feline cells. Expression of the vpg15 ligand correlated well with the reactivity of the FMC56 antibody on peripheral blood leucocytes and a panel of feline cell lines. Furthermore, the anti-human CD9 antibody reacted with murine fibroblast cells which had been transfected with high molecular weight feline DNA and immunoselected with the vpg15 antibody. FMC56 and vpg15 immunoprecipitated a similar 24,000 MW species from surface-iodinated feline cells and depletion of the vpg15 ligand from cell lysates resulted in a corresponding depletion of the FMC56 ligand. The data demonstrate that the vpg15 antibody recognizes the feline homologue of human CD9 and implicate feline CD9 as a cellular receptor for FIV.

Animals↗
PubMed1993

Induction of feline leukaemia virus-neutralizing antibodies by immunization with synthetic peptides derived from the FeLV env gene.

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.

Amino Acid Sequence↗
PubMed1993

A monoclonal antibody which blocks infection with feline immunodeficiency virus identifies a possible non-CD4 receptor.

Monoclonal antibody vpg15 detects a 24-kDa cell surface protein on feline cells permissive for infection with feline immunodeficiency virus (FIV). The antibody blocks infection of FIV-susceptible cells, and expression of the vpg15 marker is decreased in FIV-infected cells in vitro. These results suggest that the antibody may recognize an FIV receptor distinct from CD4.

Animals↗
PubMed1993

Protection of cats against feline leukemia virus by vaccination with a canarypox virus recombinant, ALVAC-FL.

Two ALVAC (canarypox virus)-based recombinant viruses expressing the feline leukemia virus (FeLV) subgroup A env and gag genes were assessed for their protective efficacy in cats. Both recombinant viruses contained the entire gag gene. ALVAC-FL also expressed the entire envelope glycoprotein, while ALVAC-FL(dl IS) expressed an env-specific gene product deleted of the putative immunosuppressive region. Although only 50% of the cats vaccinated with ALVAC-FL(dl IS) were protected against persistent viremia after oronasal exposure to a homologous FeLV isolate, all cats administered ALVAC-FL resisted the challenge exposure. Significantly, protection was afforded in the absence of detectable FeLV-neutralizing antibodies. These results represent the first effective vaccination of cats against FeLV with a poxvirus-based recombinant vector and have implications that are relevant not only to FeLV vaccine development but also to developing vaccines against other retroviruses, including human immunodeficiency virus.

Animals↗
PubMed1993

Infection with feline immunodeficiency virus is followed by the rapid expansion of a CD8+ lymphocyte subset.

Lymphocyte subset analysis was performed on specific pathogen-free cats infected with feline immunodeficiency virus (FIV). As early as 4 weeks post-infection a sharp rise in lymphocytes expressing the feline CD8 marker (fCD8) occurred. No changes were observed in feline CD4+ (fCD4+) cell number throughout this period. The expanded subset displayed reduced expression of the fCD8 marker (fCD8low) compared to the control population (fCD8high). Dual-labelling revealed increased levels of major histocompatibility complex (MHC) class II antigens on the fCD8low subset compared to the fCD8high subset. The fCD8low population appeared to persist as it was detected in cats which had been infected for a period of 18 months and which displayed significantly reduced numbers of fCD4+ lymphocytes. The data suggest that infection with FIV induces rapid alterations in the lymphocyte profile of the cat characterized by the expansion of a fCD8+ lymphocyte subset. The persistence of this population throughout the course of infection suggests that the early events in FIV infection may be of importance in the pathogenesis of the disease.

Animals↗
PubMed1992

Lymphosarcoma in experimentally induced feline immunodeficiency virus infection [corrected].

A cat experimentally infected with feline immunodeficiency virus (FIV) but known to be free of feline leukaemia virus (FeLV) developed lymphosarcoma. The lesions in the liver and kidneys were present nine months after infection, when the cat was 21 months old. The cat had no overt signs of immunodeficiency and it is suggested that the B cell activation induced shortly after FIV infection produced a large pool of proliferating lymphocytes from which the malignant cells emerged.

Animals↗
PubMed1992

A study of naturally occurring feline coronavirus infections in kittens.

Feline coronavirus is a common infection in cats, as indicated by the high prevalence of antibodies against the virus, especially in multicat households. Approximately 5 to 12 per cent of seropositive cats develop classical feline infectious peritonitis. A survey of kittens born into households of seropositive cats demonstrated the existence of healthy coronavirus carriers. Seronegative animals did not appear to excrete virus. No specific antibody titre could be linked to carrier status and some carrier cats subsequently became seronegative. The management of the kittens strongly influenced whether they became infected, and some degree of protection appeared to be conferred by maternally derived antibody. At present, feline infectious peritonitis virus and feline enteric coronavirus can only be differentiated by their different clinical histories in infected catteries. In this survey, cases of feline infectious peritonitis occurred in kittens from households where the initial presentation had been enteritis and vice versa. Therefore no difference in epidemiology could be found.

Age Factors↗
PubMed1992

Clinical and pathological findings in feline immunodeficiency virus experimental infection.

A study is described of the clinical and pathological findings in 20 specific pathogen free cats infected when 1 year old with feline immunodeficiency virus and monitored over 12 months. Cats were divided into two groups (A and B). The clinical and clinicopathological features were studied in Group A. In Group B, at 1, 2, 4, 9 and 12 months post infection two cats were necropsied. Clinically all cats developed generalised lymphadenopathy, six cats were neutropenic and five cats lymphopenic. Three cats became febrile with conjunctivitis and anterior uveitis and one of these cats ultimately developed jaundice. Postmortem examinations confirmed a generalised lymphadenopathy involving peripheral and visceral lymph nodes with concurrent stimulation of splenic white matter and mucosal lymphoid tissue of the digestive tract and conjunctiva. Within the lymph nodes there was a reactive follicular hyperplasia accompanied by a paracortical hyperplasia with an increased paracortical vascularity. Unusual features were the presence of lymphoid follicles in the bone marrow, thymus and parathyroid tissue. In addition, aggregates of lymphoid cells were found within salivary glands, kidneys, sclera and choroid of the eye. One cat developed a lymphosarcoma affecting the liver and kidneys at 36 weeks post infection. The cat with jaundice had a cholangitis with marked biliary epithelial hyperplasia.

Animals↗
PubMed1992

Decreased mitogen responsiveness and elevated tumor necrosis factor production in cats shortly after feline immunodeficiency virus infection.

We present the results of an investigation into the effects of feline immunodeficiency virus (FIV) infection on the response to mitogens and cytokine production in the first month of infection. We were able to demonstrate a depression of response of peripheral blood mononuclear cells to the mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen, with the response to pokeweed mitogen being most severely affected. The response of the cells of the spleen were affected by 10 days post infection and these could not be augmented by the addition of exogenous interleukin-2 (IL-2). The response of mesenteric lymph node cells was not affected until 20 days post infection and this could be partially restored by the addition of exogenous IL-2. IL-2 production was unaffected in peripheral blood mononuclear cells, slightly depressed in mesenteric lymph node cells and slightly elevated in spleen cells. Tumor necrosis factor levels were significantly elevated with respect to controls within 10 days of infection. These studies suggest that there are a number of changes in the immune response of FIV infected cats early in infection and this may determine the subsequent outcome of the infection.

Animals↗
PubMed1992

A recombinant feline immunodeficiency virus envelope fusion protein stimulates peripheral blood lymphocytes from naive cats to proliferate in vitro.

A region of feline immunodeficiency virus (FIV)/Glasgow-8 external envelope glycoprotein (env) incorporating the third and fourth variable regions (V3/V4) was cloned, inserted into the pGEX vector and expressed in Escherichia coli to yield milligram quantities of the recombinant polypeptide as a fusion protein with glutathione S-transferase. The fusion protein V3/V4GST was used in lymphocyte proliferation assays, where it consistently caused peripheral blood lymphocytes from naive cats to proliferate in a dose-dependent manner. Other FIV fusion proteins produced under identical conditions (V5GST and p24GST) and glutathione S-transferase alone did not cause proliferation in this system. The monoclonal antibody vpg15, which has been shown to block infection of susceptible cells in vitro, did not decrease the response to V3/V4GST. Human peripheral blood lymphocytes did not proliferate in response to V3/V4GST.

Amino Acid Sequence↗
PubMed1992

Enhancement after feline immunodeficiency virus vaccination.

Cats were vaccinated with one of the three preparations: purified feline immunodeficiency virus (FIV) incorporated into immune stimulating complexes (ISCOMs), recombinant FIV p24 ISCOMs, or a fixed, inactivated cell vaccine in quil A. Cats inoculated with the FIV ISCOMs or the recombinant p24 ISCOMs developed high titres of antibodies against the core protein p24 but had no detectable antibodies against the env protein gp120 or virus neutralising antibodies. In contrast, all of the cats inoculated with the fixed, inactivated cell vaccine developed anti-env antibodies and four of five had detectable levels of neutralising antibody. However, none of the vaccinated cats were protected from infection after intraperitoneal challenge with 20 infectious units of FIV. Indeed there appeared to be enhancement of infection after vaccination as the vaccinated cats become viraemic sooner than the unvaccinated controls, and 100% of the vaccinated cats became viraemic compared with 78% of the controls. The mechanism responsible for this enhancement remains unknown.

Adjuvants, Immunologic↗
PubMed1992

Incorporation of soluble antigens into ISCOMs: HIV gp120 ISCOMs induce virus neutralizing antibodies.

Through a process of covalent attachment of palmitic acid, we have incorporated recombinant gp120 of HIV strain IIIB into ISCOMs. Rabbits immunized with ISCOMs incorporating 10 micrograms gp120 produced high levels of gp120-specific antibody, comparable to the response to ten times as much antigen in complete Freund's adjuvant. The ISCOM-induced antisera showed virus neutralizing activity against the homologous strain, but failed to neutralize two heterologous strains of HIV-1. The antisera recognized non-conformationally determined epitopes on gp120, and antibody binding to gp120 was affected by glycosylation of the viral glycoprotein.

AIDS Vaccines↗
PubMed1992

Partial dissociation of subgroup C phenotype and in vivo behaviour in feline leukaemia viruses with chimeric envelope genes.

Feline leukaemia viruses (FeLVs) are classified into subgroups A, B and C by their use of different host cell receptors on feline cells, a phenotype which is determined by the viral envelope. FeLV-A is the ubiquitous, highly infectious form of FeLV, and FeLV-C isolates are rare variants which are invariably isolated along with FeLV-A. The FeLV-C isolates share the capacity to induce acute non-regenerative anaemia and the prototype, FeLV-C/Sarma, has strongly age-restricted infectivity for cats. The FeLV-C/Sarma env sequence is closely related to that of common, weakly pathogenic FeLV-A isolates. We now show by construction of chimeric viruses that the receptor specificity of FeLV-A/Glasgow-1 virus can be converted to that of FeLV-C by exchange of a single env variable domain, Vr1, which differs by a three codon deletion and nine adjacent substitutions. Attempts to dissect this region further by directed mutagenesis resulted in disabled proviruses. Sequence analysis of independent natural FeLV-C isolates showed that they have unique Vr1 sequences which are distinct from the conserved FeLV-A pattern. The chimeric viruses which acquired the host range and subgroup properties of FeLV-C retained certain FeLV-A-like properties in that they were non-cytopathogenic in 3201B feline T cells and readily induced viraemia in weanling animals. They also induced a profound anaemia in neonates which had a more prolonged course than that induced by FeLV-C/Sarma and which was macrocytic rather than non-regenerative in nature. Although receptor specificity and a major determinant of pathogenicity segregate with Vr1, it appears that sequences elsewhere in the genome influence infectivity and pathogenicity independently of the subgroup phenotype.

Amino Acid Sequence↗
PubMed1992

Pathogenicity of feline leukemia virus is commonly associated with variant viruses.

Many of the serious diseases resulting from feline leukemia virus (FeLV) infection are associated with the generation of novel variant viruses. The prototype FeLV-A virus is highly stable and circulates in the cat population without apparent antigenic change. However, recombination with cellular oncogenes produces viruses which cause leukemia or other malignant diseases. Other recombinants within the env genes of FeLV-A and endogenous FeLV are recognized as belonging to a second subgroup, FeLV-B, the presence of which is correlated with an increased risk of infection with FeLV and a higher incidence of leukemia. Mutants of FeLV which affect the env gene are phenotypically of a third subgroup, FeLV-C, and have a close association with erythroid aplasia. None of these viruses, apart from FeLV-B, is transmitted further in nature. Therefore the generation of these novel viruses and the production of disease is an inadvertent consequence of FeLV infection.

Anemia↗