Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Feline immunodeficiency virus (FIV) encodes the enzyme deoxyuridine-triphosphatase (DU; EC 3.6.1.23) between the coding regions for reverse transcriptase and integrase in the pol gene. Here, we report the in vivo infection of cats with a DU- variant of the PPR strain of FIV and compare its growth properties and tissue distribution with those of wild-type FIV-PPR. The results reveal several important points: (i) DU- FIV is able to infect the cat, with kinetics similar to that observed with wild-type FIV; (ii) both wild-type and DU- FIV-infected specific-pathogen free cats mount a strong humoral antibody response which is able to limit the virus burden in both groups of animals; (iii) the virus burden is reduced in the DU- FIV-infected cats, particularly in tissues such as spleen and salivary gland; and (iv) the mutation frequency in DU- FIVs integrated in the DNA of primary macrophages after 9 months of infection is approximately 5-fold greater than the frequency observed in DU- FIV DNA integrated in T lymphocytes. Mutation rate with wild-type FIV remains the same in both cell types in vivo. The dominant mutations seen in macrophages with DU- FIV are G-->A base changes, consistent with an increased misincorporation of deoxyuridine into viral DNA of DU- FIVs during reverse transcription. Because this enzyme is absent from human immunodeficiency virus type 1 and other primate lentiviruses, virus replication in cell environments with low DU activity may lead to increased mutation and contribute to the rapid expansion of the viral repertoire.
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PMID:Increased mutation frequency of feline immunodeficiency virus lacking functional deoxyuridine-triphosphatase. 763 16

In murine contact photosensitivity, a cutaneous delayed-type hypersensitivity reaction, preirradiation of the photosensitization site with UVB induced Ag-specific, afferent limb-acting, CD4+CD8- suppressor T cells (Ts). The present study examined usage of TCR V beta and production of immunosuppressive cytokines in Ts propagated in vitro. Spleen cells from UVB-preirradiated, 3,3',4',5- tetracholorosalicylanilide (TCSA)-photosensitized mice were stimulated with 3000-rad-irradiated lymph node cells (LNC) from TCSA/UVA-sensitized mice (LNCTCSA) in the presence of rIL-t. After several rounds of antigenic stimulation, a T cell line (B+TCL) consisted exclusively of CD3+CD4+CD8- V beta 7+ and V beta 13+ populations. Transfer to naive recipients of B+TCL treated with anti-V beta mAb plus complement revealed that the V beta 7+ cells suppressed both the in vivo and the in vitro aspects of contact photosensitivity to TCSA in an Ag-specific manner. The in vitro suppressive activity of B+TCL was neutralized by anti-IL-10 mAb, but not by anti-IL-4 mAb, indicating a crucial role of IL-10 in UBV-induced suppression. Upon stimulation with 3000-rad-irradiated-LNCTCSA, B+TCL released IL-4 and IL-10 but not IL-2, and V beta 7+ cells produced IL-10. The reverse transcriptase-PCR detected mRNA for IL-4 and IL-10 but not that for IL-2, IFN-gamma, or TGF-beta in B+TCL stimulated with or without concanavalin A. In accordance with the findings in B+TCL, spleen cells from UVB preirradiation plus TCSA/UVA mice contained V beta 7+ T cells that suppressed contact photosensitivity to TCSA and produced substantial amounts of IL-4 that provided a microenvironment for Th2 cell generation. We conclude that UVB preirradiation and photosensitization result in the generation of V beta 7+ Th2 cells that suppress contact photosensitivity by releasing IL-10. The dysfunction of effector Th1 cells underlying UVB suppression of delayed-type hypersensitivity seems to be due not only to altered APC function but also to counteraction of Th2 cells by Th1 cells.
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PMID:TCRV beta 7+ Th2 cells mediate UVB-induced suppression of murine contact photosensitivity by releasing IL-10. 859 33

Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that causes a spectrum of diseases remarkably similar to AIDS in HIV-infected humans. As part of this spectrum, both HIV-1 and FIV induce neurologic disorders. Because astrocytes are essential in maintaining the homeostasis of the central nervous system, we analyzed FIV for the ability to infect feline astrocytes. Through immunocytochemistry and reverse transcriptase activity, it was demonstrated that two molecular clones of FIV (FIV-34TF10 and FIV-PPR) produce a chronic low level productive infection of feline astrocyte cultures. To investigate the consequences of this infection, selected astrocyte functions were examined. Infection with FIV-34TF10 significantly decreased the ability of astrocytes to scavenge extracellular glutamate (with a peak inhibition of 74%). The effects of the infection did not appear to be a result of toxicity but rather were more selective in nature because the glucose uptake function of the infected astrocyte cultures was not altered. Our data demonstrate that FIV productively infected, at a low level, feline astrocyte cultures, and as a consequence of this infection, an important astroglial function was altered. These findings suggest that a chronic low grade infection of astrocytes may impair the ability of these cells to maintain homeostasis of the central nervous system that, in turn, may contribute to a neurodegenerative disease process that is often associated with lentivirus infections.
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PMID:Effects of feline immunodeficiency virus on astrocyte glutamate uptake: implications for lentivirus-induced central nervous system diseases. 948 37

Protoporphyria is a disease characterized by a deficiency in ferrochelatase, the terminal enzyme in the heme biosynthetic pathway, which catalyzes the chelation of iron and protoporphyrin to form heme. Clinical symptoms arise from an accumulation of protoporphyrin behind the partial enzyme block and include photosensitivity and sometimes hepatobiliary disease. Protoporphyria is described as an dominant disease, yet patients exhibit decreased ferrochelatase activities of 15-30% of normal, not 50% as might be expected. Missense, nonsense, and splicing mutations have been identified in ferrochelatase cDNA from protoporphyric patients. In this study we introduce an exon 10 deletion, an analogous mutation to that described in some protoporphyric patients, into the mouse embryonic stem (ES) cell genome via homologous recombination. Targeted ES cells were confirmed by Southern blot analysis. Expression of wild-type and exon 10-deleted mRNA was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) and cDNA sequencing. Ferrochelatase levels were analyzed by immunoblotting. Ferrochelatase activity was measured by the chelation of zinc and mesoporphyrin, and by the decrease in protoporphyrin accumulation after adding delta-aminolevulinic acid. In the exon 10 +/- ES cells there is expression of both wild-type and exon 10-deleted mRNA, a 50% decrease in cross-reactive material with an anti-ferrochelatase antibody, and an approximate 50% decrease in ferrochelatase activity compared to wild-type ES cells. Therefore, an exon 10 deletion alone is insufficient to decrease ferrochelatase activity to the levels in protoporphyric patients. This suggests that requirement of an additional mutation to decrease the expression of the wild-type allele.
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PMID:Targeted disruption of the mouse ferrochelatase gene producing an exon 10 deletion. 998 56

Murine contact photosensitivity (CPS) to 3,3',4', 5-tetrachlorosalicylanilide (TCSA) is genetically controlled mainly by the major histocompatibility complex. The H-2(b,d) haplotypes are closely associated with high responders, whereas mice with H-2(k) are low or non-responders. We found that BALB/c (H-2(d)) mice were high responders in CPS not only to TCSA but also to chlorpromazine (CPZ) and benzocaine, whereas AKR/n (H-2(k)) mice were hyporesponsive to these three photoallergic agents. To elucidate the relationship between CPS responsiveness and T helper cell induction, the expression of T-cell cytokines was examined by reverse transcriptase polymerase chain reaction in the elicited skin of CPS to the three chemicals. The expression levels of interleukin(IL)-2 and interferon-gamma mRNAs were markedly higer in BALB/c mice than AKR/n mice, whereas mRNA for IL-4 was expressed strongly in AKR/n mice. These data suggest that the hyporesponsiveness of CPS to the photoallergens in AKR/n mice is closely associated with the activation/induction of Th2 cytokines at the challenged sites.
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PMID:Expression of T-cell cytokines in challenged skin of murine allergic contact photosensitivity: low responsiveness is associated with induction of Th2 cytokines. 1080 32

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

Concurrent infection with peste des petits ruminants virus (PPRV) and pestivirus was diagnosed in stillborn twin lambs. With the flock history, the findings of epidermal syncytial cells and necrotizing bronchitis/bronchiolitis prompted testing for PPRV infection, and PPRV antigen was detected by immunohistochemistry (IHC) in the skin, lungs, kidneys, rumen, and thymus. Macroscopic anomalies that were typical of border disease included scoliosis, brachygnathism, prognathism, arthrogryposis, hydranencephaly, cerebellar hypoplasia, and hairy fleece; pestiviral antigen was detected by IHC in the brain, liver, lungs, and kidneys. Tissues from both lambs were positive by reverse transcriptase-polymerase chain reaction (RT-PCR) for PPRV and pestivirus. To the authors' knowledge, PPR has not been reported previously as a congenital infection or in combination with pestiviral infection.
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PMID:Concurrent peste des petits ruminants virus and pestivirus infection in stillborn twin lambs. 1842 32

This study was designed to characterize N gene sequences of peste des petits ruminants virus (PPRV) isolates circulating in Pakistan and to evaluate the efficacy of available diagnostic assays on local isolates. During the study period, a total of sixty PPR outbreaks were investigated. A total of 20 selected samples from these outbreaks were sequenced for N gene. The result analysis and the phylogenetic trees indicated two different viral groups in N gene: one was closer to China and Tajikistan, while other group was similar to isolates from Iran and Saudi Arabia. Efficacy of three commercially available tests for the antigen detection of PPR, that is, peste test, enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) was compared. Keeping PCR as gold standard, sensitivity was calculated as 85% and 57% and specificity was calculated as 83% and 79% for ELISA and peste test, respectively. Value of K for ELISA was 0.67 which indicates good agreement between ELISA and RT-PCR. Value of K for peste test was 0.33 which indicates fair agreement between peste test and RT-PCR. In conclusion, study provides premier information about the use of different diagnostic tests and molecular situation of PPRV in Pakistan.
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PMID:Genetic characterization of peste des petits ruminants virus (Pakistani isolates) and comparative appraisal of diagnostic assays. 3225 96