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O Jarrett

Publications and source records attributed to O Jarrett.

At least 37 records · Page 2Linked to original sources
PubMed1998

Feline immunodeficiency virus (FIV)-associated lymphoma: a potential role for immune dysfunction in tumourigenesis.

To determine the potential role of immune dysfunction in feline immunodeficiency virus (FIV)-associated lymphomagenesis, we present the results of immunological monitoring during the chronic phase of experimental FIV infection in two cats which subsequently developed lymphoma. In one cat, C1, cell-mediated immunity was depressed throughout the monitoring period but particularly from 125-200 weeks post-infection (pi), when this cat demonstrated profoundly impaired lymphocyte blastogenesis and markedly increased interleukin-1 (IL-1) production compared to age-matched, uninfected control cats. Lymphocyte function in the other cat, C2, was preserved to a greater degree. Alterations in the levels of immunoglobulin isotypes M, A and G in CD4+-, CD8+- and CD21+-lymphocyte sub-sets were demonstrated in both cats. Southern blot analysis revealed the presence of integrated FIV-provirus in tumour DNA from C2 but not C1 indicating a possible direct role for the virus in the former case only. In this study we have characterised, for the first time, the FIV-induced immune dysfunction in cats which developed lymphoma, demonstrating potential indirect mechanisms of tumourigenesis.

Animals↗
PubMed1998

A comparison of DNA amplification, isolation and serology for the detection of Chlamydia psittaci infection in cats.

Chlamydia psittaci is a significant cause of conjunctivitis in cats, but can be difficult to diagnose owing to the small number of organisms in conjunctival swabs. In the United Kingdom laboratory diagnosis is based on three techniques: isolation of the infectious organism, amplification of chlamydial DNA by the polymerase chain reaction (PCR) or the detection of anti-chlamydial antibodies by immunofluorescence assay. To determine the most sensitive method these techniques were compared in the field. The PCR based on previously published protocols was less sensitive than isolation, but by modifying the protocol its sensitivity was increased by a factor of 25 to 1250 and it was then more sensitive than isolation. The modified PCR detected chlamydia in samples containing non-infectious organisms. Serology was of limited use in predicting which cats shed C psittaci although seronegative cats were negative by PCR and isolation. The modified PCR was the most sensitive and robust method for confirming C psittaci infection in cases of conjunctivitis in pet cats.

Animals↗
PubMed1998

Molecular and immunophenotypical characterization of a feline immunodeficiency virus (FIV)-associated lymphoma: a direct role for FIV in B-lymphocyte transformation?

We describe the histopathological, immunohistochemical, and molecular characterization of a lymphoma arising in a 7-year-old cat following experimental infection with feline immunodeficiency virus (FIV). The tumor was high grade and of B-cell lineage. The transformed cell had an immature phenotype (CD79a+, CD79b-, CD21-, immunoglobulin heavy and light chain negative), confirmed by antigen receptor gene analysis, which showed germ line configuration. Single-copy, clonally integrated FIV provirus was detected in tumor genomic DNA. FIV p24 antigen was not detected in tumor cells by immunostaining. This study provides the first evidence that the feline lentivirus may play a direct role in cell transformation under certain circumstances.

Animals↗
PubMed1998

The receptor binding site of feline leukemia virus surface glycoprotein is distinct from the site involved in virus neutralization.

The external surface glycoprotein (SU) of feline leukemia virus (FeLV) contains sites which define the viral subgroup and induce virus-neutralizing antibodies. The subgroup phenotypic determinants have been located to a small variable region, VR1, towards the amino terminus of SU. The sites which function as neutralizing epitopes in vivo are unknown. Recombinant SU proteins were produced by using baculoviruses that contained sequences encoding the SUs of FeLV subgroup A (FeLV-A), FeLV-C, and two chimeric FeLVs (FeLV-215 and FeLV-VC) in which the VR1 domain of FeLV-A had been replaced by the corresponding regions of FeLV-C isolates. The recombinant glycoproteins, designated Bgp70-A, -C, -215, and -VC, respectively, were similar to their wild-type counterparts in several immunoblots and inhibited infection of susceptible cell lines in a subgroup-specific manner. Thus, Bgp70-A interfered with infection by FeLV-A, whereas Bgp70-C, -VC, and -215 did not. Conversely, Bgp70-C, -VC, and -215 blocked infection with FeLV-C, while Bgp70-A had no effect. These results indicate that the site on SU which binds to the FeLV cell surface receptor was preserved in the recombinant glycoproteins. It was also found that the recombinant proteins were able to bind naturally occurring neutralizing antibodies. Bgp70-A, -VC, and -215 interfered with the action of anti-FeLV-A neutralizing antibodies, whereas Bgp70-C did not. Furthermore, Bgp70-C interfered with the action of anti-FeLV-C neutralizing antibodies, while the other proteins did not. These results indicate that the neutralizing epitope(s) of FeLV SU lies outside the subgroup-determining VR1 domain.

Animals↗
PubMed1998

DNA vaccination affords significant protection against feline immunodeficiency virus infection without inducing detectable antiviral antibodies.

To test the potential of a multigene DNA vaccine against lentivirus infection, we generated a defective mutant provirus of feline immunodeficiency virus (FIV) with an in-frame deletion in pol (FIVDeltaRT). In a first experiment, FIVDeltaRT DNA was administered intramuscularly to 10 animals, half of which also received feline gamma interferon (IFN-gamma) DNA. The DNA was administered in four 100-microg doses at 0, 10, and 23 weeks. Immunization with FIVDeltaRT elicited cytotoxic T-cell (CTL) responses to FIV Gag and Env in the absence of a serological response. After challenge with homologous virus at week 26, all 10 of the control animals became seropositive and viremic but 4 of the 10 vaccinates remained seronegative and virus free. Furthermore, quantitative virus isolation and quantitative PCR analysis of viral DNA in peripheral blood mononuclear cells revealed significantly lower virus loads in the FIVDeltaRT vaccinates than in the controls. Immunization with FIVDeltaRT in conjunction with IFN-gamma gave the highest proportion of protected cats, with only two of five vaccinates showing evidence of infection following challenge. In a second experiment involving two groups (FIVDeltaRT plus IFN-gamma and IFN-gamma alone), the immunization schedule was reduced to 0, 4, and 8 weeks. Once again, CTL responses were seen prior to challenge in the absence of detectable antibodies. Two of five cats receiving the proviral DNA vaccine were protected against infection, with an overall reduction in virus load compared to the five infected controls. These findings demonstrate that DNA vaccination can elicit protection against lentivirus infection in the absence of a serological response and suggest the need to reconsider efficacy criteria for lentivirus vaccines.

Amino Acid Sequence↗
PubMed1997

Value of alpha 1-acid glycoprotein in the diagnosis of feline infectious peritonitis.

Feline infectious peritonitis (FIP) is notoriously difficult to differentiate from the many other diseases with similar clinical signs and at present the only conclusive diagnostic test is the histopathological examination of a biopsy. The potential value of raised levels of the acute phase reactants, alpha 1-acid glycoprotein (AGP) and haptoglobin in the diagnosis of the disease was investigated. The concentrations of the two proteins were determined in serum samples from healthy cats and gave reference ranges of 0.1 to 0.48 g/litre and 0.04 to 3.84 g/litre, respectively. Levels of AGP greater than 1.5 g/litre in serum, plasma or effusion samples were found to be of value in distinguishing field cases of FIP from cats with similar clinical signs and differentiated these two groups of cats more effectively than the albumin:globulin ratio. The concentration of haptoglobin was higher in cats with FIP than in the group of healthy cats, but this protein was not of value in the diagnosis of FIP. Serum samples from feline immunodeficiency virus-infected cats were also analysed for these proteins and their concentrations were significantly elevated, illustrating that raised levels of AGP and haptoglobin are not pathognomonic for FIP.

Animals↗
PubMed1997

Comparative efficiency of feline immunodeficiency virus infection by DNA inoculation.

Direct inoculation of genetic material in DNA form is a novel approach to vaccination that has proved efficacious for a number of viral agents. We are interested in the potential of this approach for the delivery of vaccines based on attenuated or replication-defective retroviruses. Toward this goal, we tested the effect of intramuscular inoculation of a plasmid containing the entire genome of feline immunodeficiency virus (FIV-Petaluma, F14 clone). DNA delivery was compared with intramuscular or intraperitoneal inoculation of virus reconstituted from the same molecular clone. The outcome was monitored by serological analysis and quantitative virus load determination over a 31-week period. DNA inoculation was found to be a reliable means of infection, although seroconversion and the rise in PBMC virus load were delayed relative to intramuscular or intraperitoneal inoculation of virus. At 31 weeks, similar levels of proviral DNA were detected in central lymphoid tissue of all infected animals. In conclusion, DNA inoculation of proviral DNA will be of use as a novel method of cell-free virus challenge and may have further potential for the delivery of lentiviral vaccines.

Animals↗
PubMed1997

Feline leukaemia virus proviral DNA detected by polymerase chain reaction in antigenaemic but non-viraemic ('discordant') cats.

A nested polymerase chain reaction (PCR) was established to detect exogenous feline leukaemia virus (FeLV) proviral DNA in feline peripheral blood leukocytes (PBL). The assay detected a single copy of plasmid DNA of an infectious molecular clone of FeLV subgroup A in the sample by ethidium bromide staining in agarose gels. The utility of the nested PCR in the diagnosis of FeLV infections was compared with the detection of FeLV p27 antigen by enzyme-linked immunosorbent assay (ELISA) and virus isolation (VI). FeLV genomes were detected by PCR in all 4 samples that were positive by ELISA and VI but in none of 7 samples that were negative by the two methods. FeLV genomes were found by PCR in 13 of 39 samples from cats that were antigenaemic but from which no virus was isolated ('discordant' cats). These results demonstrated that a proportion of discordant cats harboured FeLV genome in their PBL.

Animals↗
PubMed1997

Evaluation of commercially available assays of neopterin and beta 2-microglobulin for the assessment of disease progression in FIV-infected cats.

Serum or plasma samples from cats at different stages of feline immunodeficiency (FIV) infection and from uninfected cats were tested using immunoassays designed to detect human neopterin and beta 2-microglobulin (beta 2M). The results obtained from the anti-human neopterin assay did not correlate with infection status, time post-infection, fCD4 count or clinical picture. Feline samples gave negative results in the anti-human beta 2M assay. The assay kits used in this study are not suitable for the determination of the effect of FIV infection on immune activation markers in the cat.

Animals↗
PubMed1997

Serological analysis of feline calicivirus isolates from the United States and United Kingdom.

The antigenic relationship of 181 feline calicivirus (FCV) isolates from the United States (USA) and United Kingdom (UK) to 5 reference viruses, representing 2 vaccine strains (F9 VacNor, 2280) and 3 field strains (H, J, TN) was determined by a neutralization assay using two standardized dilutions of reference sera. A comparison between USA and UK isolates indicated that significantly fewer UK isolates could be neutralized by sera specific for each of the reference strains. Isolates from the USA were also analyzed based on the time period and geographical location from which they were derived. Analysis of the cross-neutralization results for isolates derived from the USA indicated that no single reference strain was predominant in all the geographical locations, however, antisera specific to strains 2280, H and J neutralized the highest number of isolates overall. Analysis of the neutralization patterns based on the time period from which the isolates were derived indicated that F9 VacNor was antigenically similar to 86% of feline caliciviruses isolated in 1958-1979. This number decreased to 43% for isolates derived in 1980-1995. By contrast, the J strain maintained its antigenic relatedness to approximately 75% of representative FCV isolates circulating during the last 40 years.

Animals↗
PubMed1997

Vaccination with a feline immunodeficiency virus multiepitopic peptide induces cell-mediated and humoral immune responses in cats, but does not confer protection.

Cats were immunized with a 46-residue multiepitopic synthetic peptide of feline immunodeficiency virus (FIV) comprising immunodominant epitopes present in the third variable domain of the envelope glycoprotein, transmembrane glycoprotein (TM), and p24 Gag core protein, using Quil A as an adjuvant. All vaccinated cats developed a humoral response which recognized the synthetic peptide immunogen and the intact viral core and envelope proteins. A FIV Gag- and Env-specific effector cytotoxic T-lymphocyte response was also detected in the peripheral blood of vaccinated cats, which peaked at week 30. This response appeared to be major histocompatibility complex restricted. Epitope mapping studies revealed that both the cellular and humoral immune responses were directed principally to a peptide within the TM glycoprotein, CNQNQFFCK. However, vaccination did not confer protection when cats were challenged with the Petaluma isolate of FIV at week 35.

Adjuvants, Immunologic↗
PubMed1996

Env-specific CTL predominate in cats protected from feline immunodeficiency virus infection by vaccination.

Animal models of HIV-1 have a key role to play in elucidation of the cellular mechanisms responsible for protective immunity. Vaccination of domestic cats with whole inactivated feline immunodeficiency virus (FIV) elicits virus-neutralizing Abs and virus-specific CTL in the peripheral blood and lymphoid organs and affords protection from homologous virus challenge. In the present study we confirm the induction of virus-specific CTL following immunization with whole inactivated FIV vaccine and demonstrate that cats are protected for up to 1 yr following vaccination. Long term protection in vaccinated cats correlates with both higher levels of FIV Env-specific CTL in the peripheral blood following vaccination and the presence of FIV Env-specific memory CD8+ CTL in the lymph nodes, which persist for up to 1 yr following challenge in the absence of detectable virus. The CTL responses observed in vaccinated protected cats differ qualitatively from those in FIV-infected cats. The latter cats either do not generate a memory CTL response or exhibit a Gag-specific memory CTL response. These results show that the protective immunity observed in whole inactivated virus-vaccinated cats is associated with the induction of high levels of Env-specific CTL activity.

Animals↗