Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cleavage of the envelope glycoprotein precursor gp160 of HIV-1 is a prerequisite for the infectivity of HIV-1, and occurs at least in part before gp160 reaches the cell surface. Kexin/subtilisin-related endopeptidases are proposed enzyme candidates for this intracellular processing. In this study, we reveal the possibility that plasminogen binds to the cell surface and part of gp160 escaping intracellular processing is cleaved by plasmin extracellularly. Plasmin cleaves gp160 precisely at the C-terminal arginine residue of gp120, and the processing is effectively inhibited by an analogue peptide of the cleavage motif (RXK/RR) and by plasmin inhibitors.
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PMID:The extracellular processing of HIV-1 envelope glycoprotein gp160 by human plasmin. 992

To date, the phatophysiology of hemorrhagic dengue is still unknown and hypotheses which aim to explain the unfortunate cases of the disease (hemorrhagic fever/shock syndrome) are based on epidemiological data and favor the notion of the participation of heterotypic non-neutralizing antibodies during the course of secondary infection (immunologic status of the host). However, cases of hemorrhagic dengue have been reported during the course of primary infections. We propose that the dengue virus, specifically the envelope glycoprotein can participate directly in the installation of the hemorrhagic phenomenon by means of the binding and activation of plasminogen (PLG) as condition previous to the development of the fibrinolytic process. Based on this hypothesis, we evaluated the biological activity of some viral isolates proceeding from hemorrhagic and from dengue fever cases in an in vitro model of fibrinolysis. Dengue isolates were capable of activating PLG. The plasmin generated specifically degraded the fibrin/fibrinogen molecule. This catalytic process can be prevented by the presence of the specific plasmin inhibitor, alpha-2-antiplasmin, for virus isolates from dengue fever, but not for isolates associated with dengue hemorrhagic disease, favoring the exacerbation of the fibrinolytic activity. This new approach allows us to suggest the importance of viral factors in the dengue hemorrhagic fever.
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PMID:Participation of the Dengue virus in the fibrinolytic process. 1112 36

We recently demonstrated that fibrin hydrogels can be used as vehicles for efficient lentivirus gene delivery. Gene transfer in fibrin gels was strongly dependent on matrix degradation by target cells but a fraction of lentiviral particles diffused out of the gels over time compromising spatial control of gene transfer. To overcome this challenge, we engineered lentiviral particles that bind covalently to fibrin during polymerization. To this end, we fused into the viral envelope glycoprotein (VSV-G) peptide domains that are recognized by factor XIII and protease cleavage sites that are recognized by plasmin. Lentivirus pseudotyped with the modified envelopes bound to fibrinogen in a factor XIII dose dependent manner and was released upon plasmin treatment. The peptide/VSV-G fusion envelope variants did not compromise the transduction efficiency of the resulting virus except when lacking any flexible linkers separating the peptide from the VSV-G envelope. Diffusion of virus from the gels decreased dramatically, especially at high concentrations of FXIII, even for fibrin gels with low fibrinogen concentration that were loaded with high titer virus. Lentivirus arrays prepared with fibrin-conjugated lentivirus yielded highly efficient gene transfer that was confined to virus-containing fibrin spots. As a result, signal/noise ratio increased and cross-contamination between neighboring sites was minimal. Finally, in addition to lentivirus microarrays this strategy may be used to achieve spatially-controlled gene transfer for therapeutic applications.
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PMID:Engineering fibrinogen-binding VSV-G envelope for spatially- and cell-controlled lentivirus delivery through fibrin hydrogels. 2129 11