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)

Visna/maedi virus (VMV) causes severe encephalitis and a progressive demyelinating disease in sheep. Previous in vitro studies have demonstrated that VMV-infection leads to apoptosis in sheep choroid plexus cells (SCPC) via induction of both intrinsic and extrinsic pathways with subsequent activation of caspases. 3' azido-2',3'-deoxythymidine (AZT) is a potent and selective Human immunodeficiency virus 1 (HIV-1) reverse transcriptase inhibitor, widely used in antiretroviral therapy; however its effects on retrovirus-induced apoptosis are unknown. Using diverse strategies to detect apoptosis, we analysed the broad range effect of AZT treatment on inhibition of VMV-induced apoptosis. First, we found that AZT treatment inhibited the appearance of characteristic apoptotic morphologic changes documented by DAPI staining and oligonucleosomal DNA laddering. Secondly, AZT treatment inhibited caspase cascade and resulted in (i) diminished caspase-3, -8 and -9 activities and (ii) no fluorescein isothiocynate-[VAD]-fluoromethylketone (FITC-VAD-FMK) in situ labelling in VMV-infected cells treated with AZT. Finally, immunocytochemistry indicated that VMV-infection of SCPC induced the subsequent release of apoptosis inducing factor (AIF), whereas AZT treatment inhibited AIF leakage. Consequently, the anti-apoptotic effects of AZT are not restricted, since AZT treatment blocks all the apoptotic pathways induced during VMV-infection.
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PMID:AZT inhibits Visna/maedi virus-induced apoptosis. 1499 45

In small ruminant lentivirus infections, cellular immune responses are diminished in clinically affected animals. The underlying mechanisms for this are unknown. In this study, we tested the hypothesis that alterations in expression of the co-stimulatory molecules B7-1 and B7-2 are involved in infections with Visna/Maedi virus (VMV), the prototype lentivirus of sheep. We studied B7 expression levels ex vivo in peripheral blood mononuclear cells (PBMCs), determining B7 RNA levels by real time reverse transcriptase polymerase chain reaction in asymptomatic as well as clinically affected VMV-seropositive sheep. The levels of both B7 molecules were increased in VMV-seropositive asymptomatic sheep. However, in VMV clinically affected sheep, the level of CD80 (but not CD86) was low compared with the level in uninfected sheep (p < 0.05). CD80 and CD86 RNA levels were associated with the ability of PBMCs to respond to VMV gag antigens (p14, p17, and p25) by proliferation, with most seropositive asymptomatic sheep showing positive proliferative responses but clinically affected sheep showing no response. The response to p25 in clinically affected animals was increased by the addition of interleukin-2 to the cultures. Decreased recall responses to unrelated antigens (assessed by production of interferon-gamma) were also found in clinically affected sheep. Thus, among seropositive sheep, decreased B7-1 (CD80) RNA levels and diminished antigen-specific cellular immune responses in PBMCs point to a VMV disease status, whereas increased CD80 and CD86 levels and augmented cellular responses are linked to asymptomatic infection.
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PMID:Association of CD80 and CD86 expression levels with disease status of Visna/Maedi virus infected sheep. 1815 34


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