Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0349506 (photosensitivity)
 4,145 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether live-attenuated feline immunodeficiency virus (FIV) proviral DNA will induce protective immunity, a plasmid clone constructed with a FIV provirus containing a deletion in the viral accessory gene vif (FIV-pPPR-Deltavif) was inoculated as proviral DNA into four cats by the intramuscular route. After 43 weeks, these cats were boosted with the same proviral plasmid. Analysis of peripheral blood mononuclear cells at several time points after the primary and booster inoculations revealed no detectable virus or proviral DNA. At 6 weeks after the booster, immunized cats and additional naive control cats were challenged with a cell-free preparation of the infectious biological isolate FIV-PPR by the intraperitoneal route. Virus was detected after challenge in unvaccinated control cats but not in any of the FIV-pPPR-Deltavif-immunized cats. Both FIV Gag- and Env-specific cytotoxic T lymphocyte (CTL) activities were detected in peripheral blood cells of control cats after challenge infection, whereas only one of four cats immunized with FIV-pPPR-Deltavif DNA exhibited a measurable CTL response to Env following challenge. Although anti-Gag antibodies were not detected after both proviral DNA inoculation and challenge, anti-Env antibodies were found in FIV-pPPR-Deltavif-immunized cats after vaccination as well as after challenge. These findings indicate that inoculation with FIV-pPPR-Deltavif proviral DNA induced resistance to challenge with infectious FIV and that a vif deletion mutant may provide a relatively safe attenuated lentiviral vaccine.
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PMID:Protective immunity against feline immunodeficiency virus induced by inoculation with vif-deleted proviral DNA. 1089 9

The effects of virus dose on host response were evaluated for the PPR strain of feline immunodeficiency virus (FIV-PPR). Specific pathogen-free cats were inoculated intravenously with 50, 250 or 1250 TCID(50) of FIV-PPR. Two weeks after inoculation, virus was detected in 10(6) peripheral blood mononuclear cells (PBMCs) of all infected animals, and the CD4(+):CD8(+) T lymphocyte ratios fell from greater than 2 to approximately 1 in all infected animals within the first 8 weeks after infection. Provirus detected in all groups using PCR and 10(3) PBMC was biphasic. Nine of 15 animals were positive between weeks 2 and 4 p.i. and 14 of 15 were positive by week 8 p.i. Transient lymphadenopathy was detected in most cats receiving 1250 TCID(50) and the 250 TCID(50) of virus, whereas no lymphadenopathy was detected in the 50 TCID(50) group or the five uninfected cats. Animals that had received the largest dose seroconverted earliest (on average at week 4.0) and those receiving the least seroconverted last (on average at week 5.6). Neither neutropenia nor lymphopenia were detected. FIV-specific CTL responses of memory effector cells could be detected in animals receiving all three doses but was highly variable among individual animals. Neurological manifestations determined after 15 weeks p.i. were observed in most infected cats, including two of the three that had received 50 TCID(50) of virus. However, the observed neurologic abnormalities were markedly less severe in the animals receiving the least amount of virus. Therefore, lymphadenopathy and neurologic signs of illness were less severe and seroconversion was slower in the animals that received the lowest dose compared with those receiving the 250 and 1250 TCID(50) doses of the FIV-PPR strain.
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PMID:Dose response studies of acute feline immunodeficiency virus PPR strain infection in cats. 1100 May 29

To better understand the correlation of mucosal and systemic immune responses with lentiviral containment, we contrasted the early mucosal and systemic immune responses induced by vaginal versus intravenous exposure of cats to feline immunodeficiency virus (FIV) isolates of differing pathogenicity and clade (i.e., FIV-B-2542 and FIV-A-PPR). We found that despite divergence in viral genotype, the mucosal and systemic immune responses induced differed more with route of exposure than virus isolate. In intravenously exposed cats, Gag-specific antibody (both IgG and IgA isotype) predominated in the serum, saliva, and vaginal wash fluid irrespective of infecting virus isolate. While Env-specific responses were more variable, they were more often detected in vaginally infected cats. Both IgG and IgA directed against Gag and Env were consistently present in vaginal wash fluids independent of route of infection or virus isolate. FIV Gag- and Env-specific cytotoxic lymphocytes (CTLs) were detected in blood and tissue lymphocytes of cats infected with either virus strain but were greatest in intravenously infected animals. Likewise, FIV-specific CTLs were detected in CD8(+) vaginal lymphocytes of animals infected by either route but were also more frequent in intravenously inoculated animals. In summary, we found qualitative differences in the immune responses following vaginal infection but no evidence (1) that mucosal immune responses were enhanced in vaginally exposed cats, (2) that local mucosal infection led to measurably greater immune responses in either compartment; or (3) that more prominent immune responses correlated with lower viral burden.
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PMID:Feline immunodeficiency virus Gag- and Env-specific immune responses after vaginal versus intravenous infection. 1178 28

To determine the influence of route of virus exposure on early pathogenesis of feline immunodeficiency virus (FIV) infection, cats were exposed to either of two FIV isolates (FIV-B-2542 or FIV-A-PPR) by vaginal or intravenous (IV) inoculation. Exposure to either virus clade by either route of inoculation resulted in vaginal and systemic infection. Peak plasma viremia and tissue proviral burden were 1-3 log(10) greater in cats infected with FIV-B-2542 vs. FIV-A-PPR, irrespective of inoculation route. Plasma RNA levels paralleled provirus titers in FIV-B-2542-infected cats and were highest in those exposed IV. In contrast, plasma RNA titers were higher in cats infected vaginally with FIV-A-PPR than in those infected IV. Despite early differences, PBMC provirus titers were similar in all groups by 9 weeks postinfection. In cats infected IV, but not vaginally, CD4(+) lymphocyte counts declined significantly independent of the magnitude of viremia. Mitogen-induced lymphoproliferation was decreased in all infected cats regardless of CD4(+) cell counts; this decline correlated with the magnitude of peak plasma viremia in FIV-B-2542, but not FIV-A-PPR, infected cats. These results establish that the kinetics of early FIV infection differ with route of exposure as well as virus isolate and that properties extrapolated from one virus isolate may not be universal.
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PMID:Kinetics of early FIV infection in cats exposed via the vaginal versus intravenous route. 1183 57

Chronic actinic dermatitis (CAD) is a photosensitivity disorder marked by severe eczematous lesions on exposed areas. Although associations with contact dermatitis, atopic dermatitis, and human immunodeficiency virus (HIV) have been suggested, its pathogenesis remains unknown. CAD is often refractory, and systemic administration of cyclosporin A has been the treatment of choice. Recently, topical tacrolimus therapy has been reported to be effective. We report the efficacy of topical tacrolimus treatment in a CAD patient who also had the complication of idiopathic leukopenia. A phototest showed marked suppression of erythema formation in the skin pre-treated with tacrolimus before UVB radiation but not in the skin treated after the irradiation. Therefore, it is suggested that tacrolimus may prevent UV-B induced erythema by suppressing a very early phase of the inflammatory process in CAD.
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PMID:The successful use of topical tacrolimus treatment for a chronic actinic dermatitis patient with complications of idiopathic leukopenia. 1468 38

CD8+ T-cell-mediated suppression of feline immunodeficiency virus (FIV) replication has been described by several groups, although the mechanisms of activation and conditions for viral suppression vary with the methodologies. We have previously reported that CD8+ T-cell-mediated suppression of FIV replication required inducer cell stimulation of the effector cells. The focus of the present study was to examine the essential role of inducer cells required for the induction of this soluble anti-FIV activity. Both FIV-PPR-infected T cells and feline skin fibroblasts (FSF) infected with an alphavirus vector expressing FIV capsid or the irrelevant antigen lacZ, stimulated autologous or heterologous effector cells to produce supernatants that suppressed FIV replication. Thus, induction of this suppression of FIV replication did not strictly require autologous inducer cells and did not require the presence of FIV antigen. Anti-viral activity correlated with the presence of CD8+ T cells. Suppression was maximal when the inducer cells and the effector cells were in contact with each other, because separation of the inducer and effector cells by a 0.45-microm membrane reduced FIV suppression by approximately 50%. These findings emphasize the importance for membrane antigen interactions and cytokines in the optimal induction of effector cell synthesis of the soluble anti-FIV activity.
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PMID:The role of inducer cells in mediating in vitro suppression of feline immunodeficiency virus replication. 1500 63

In vivo tests were performed to assess the influence of the protease inhibitor TL-3 on feline immunodeficiency virus (FIV)-induced central nervous system (CNS) deficits. Twenty cats were divided into four groups of five animals each. Group 1 received no treatment, group 2 received TL-3 only, group 3 received FIV strain PPR (FIV-PPR) only, and group 4 received FIV-PPR and TL-3. Animals were monitored for immunological and virological status, along with measurements of brain stem auditory evoked potential (BAEP) changes. Groups 1 and 2 remained FIV negative, and groups 3 and 4 became virus positive and seroconverted by 3 to 5 weeks postinoculation. No adverse effects were noted with TL-3 only. The average peak viral load for the virus-only group 3 animals was 1.32 x 10(6) RNA copies/ml, compared to 6.9 x 10(4) copies/ml for TL-3-treated group 4 cats. Group 3 (virus-only) cats exhibited marked progressive delays in BAEPs starting at 2 weeks post virus exposure, which is typical of infection with FIV-PPR. In contrast, TL-3-treated cats of group 4 exhibited BAEPs similar to those of control and drug-only cats. At 97 days postinfection, treatments were switched; i.e., group 4 animals were taken off TL-3 and group 3 animals were treated with TL-3. BAEPs in group 3 animals returned to control levels, while BAEPs in group 4 animals remained at control levels. After 70 days on TL-3, group 3 was removed from the drug treatment regimen. Delays in BAEPs immediately increased to levels observed prior to TL-3 treatment. The findings show that early TL-3 treatment can effectively eliminate FIV-induced changes in the CNS. Furthermore, TL-3 can counteract FIV effects on the CNS of infected cats, although continued treatment is required to maintain unimpaired CNS function.
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PMID:Resolution and prevention of feline immunodeficiency virus-induced neurological deficits by treatment with the protease inhibitor TL-3. 1507 33

We have derived and characterized a highly pathogenic molecular isolate of feline immunodeficiency virus subtype C (FIV-C) CABCpady00C. Clone FIV-C36 was obtained by lambda cloning from cats that developed severe immunodeficiency disease when infected with CABCpady00C (Abbotsford, British Columbia, Canada). Clone FIV-C36 Env is 96% identical to the noninfectious FIV-C isolate sequence deposited in GenBank (FIV-Cgb; GenBank accession number AF474246) (A. Harmache et al.) but is much more divergent in Env when compared to the subgroup A clones Petaluma (34TF10) and FIV-PPR (76 and 78% divergence, respectively). Clone FIV-C36 was able to infect freshly isolated feline peripheral blood mononuclear cells and primary T-cell lines but failed to productively infect CrFK cells, as is typical of FIV field isolates. Two-week-old specific-pathogen-free cats infected with FIV-C36 tissue culture supernatant became PCR positive and developed severe acute immunodeficiency disease similar to that caused by the uncloned CABCpady00C parent. At 4 to 5 weeks postinfection (PI), 3 of 4 animals developed CD4(+)-T-cell depletion, fever, weight loss, diarrhea, and opportunistic infections, including ulcerative stomatitis and tonsillitis associated with abundant bacterial growth, pneumonia, and pyelonephritis, requiring euthanasia. Histopathology confirmed severe thymic and systemic lymphoid depletion. Interestingly, the dam also became infected with a high viral load at 5 weeks PI of the kittens and developed a similar disease syndrome, requiring euthanasia at 11 weeks PI of the kittens. This constitutes the first report of a replication-competent, infectious, and pathogenic molecular clone of FIV-C. Clone FIV-C36 will facilitate dissection of the pathogenic determinants of FIV.
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PMID:Characterization of a highly pathogenic molecular clone of feline immunodeficiency virus clade C. 1530 94

The surface glycoprotein (gp95) of the feline immunodeficiency virus (FIV) binds in a strain-specific manner to several cell surface molecules, including CXCR4, heparan sulfate proteoglycans (HSPGs), DC-SIGN, and a 43-kDa cell surface receptor on T cells recently identified as CD134 by M. Shimojima et al. (Science 303:1192-1195, 2004). CXCR4 is the entry receptor in all known cases, and the other molecules act as binding receptors to help facilitate infection. In this report, we confirm and extend the findings regarding CD134 as a primary receptor for FIV. In addition, we show that temperature critically influences the binding properties of FIV gp95 to CXCR4 and HSPGs. The data show that gp95 of the field strain FIV-PPR bound to CXCR4 at 22 degrees C, whereas binding was not detected at 4 degrees C. In contrast, binding of the laboratory adapted FIV-34TF10 gp95 was observed at either 4 degrees C or 22 degrees C, albeit at increased levels at the higher temperature. The level of CXCR4 increased after the temperature was switched from 4 to 22 degrees C, whereas the level of HSPGs decreased, resulting in higher binding of gp95 from both strains to CXCR4 and lower binding of gp95 of FIV-34TF10 to HSPGs (FIV-PPR gp95 does not bind to these molecules). The findings also show that HSPGs facilitate the CXCR4-mediated infectivity of CrFK and G355-5 cells by FIV-34TF10. These two nonlymphoid cell lines express very low levels of CXCR4 and are permissive to FIV-34TF10 but not to productive infection by FIV-PPR. However, overexpression of human CXCR4 in CrFK or G-355-5 cells resulted in extensive cell fusion and infection by FIV-PPR. Taken together, these findings indicate that factors that increase the effective concentration of CXCR4 enhance FIV infectivity and may involve (i) temperature or ligand-induced conformational changes in CXCR4 that enhance SU binding, (ii) coreceptor interactions with gp95 that either alter gp95 conformation to enhance CXCR4 binding and/or raise the localized concentration of receptor or ligand, or (iii) direct increase in CXCR4 concentration via overexpression.
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PMID:Factors that increase the effective concentration of CXCR4 dictate feline immunodeficiency virus tropism and kinetics of replication. 1530 9

Feline immunodeficiency virus infection of cats provides a model to elucidate mechanisms of lentiviral pathogenesis. We isolated a non-domestic FIV from a Pallas' cat, FIV-Oma, which replicates in feline PBMCs and CRFK cells. To gain insights into FIV pathogenesis, we compared rates of viral replication and apoptosis of FIV-Oma with FIV-PPR in the MYA-1 T-cell line. To minimize heterogeneity of virus, infections were initiated with virus derived from molecular clones. Viral DNA and RNA levels, assessed by qPCR and qRT-PCR, apoptosis, and supernatant reverse transcriptase were slower in FIV-Oma infections. Immunostaining for cellular Gag showed that few cells were productively infected. The majority of cells infected with either virus instead became apoptotic. Apoptosis was detectable within 6 h PI, suggesting activation of a signaling pathway. We propose that apoptosis is due to interaction of virus with cells, and is the usual outcome of infection by cytopathic FIVs in these cells.
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PMID:Comparative replication kinetics of two cytopathic feline lentiviruses ex vivo. 1568 Apr 17


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