Stimulation of the HIV-1 integrase enzymatic activity and cDNA integration by a peptide derived from the integrase protein

Biopolymers ◽  
2010 ◽  
pp. NA-NA
Author(s):  
Aviad Levin ◽  
Zvi Hayouka ◽  
Markus Helfer ◽  
Ruth Brack-Werner ◽  
Assaf Friedler ◽  
...  
1977 ◽  
Vol 38 (02) ◽  
pp. 0475-0485 ◽  
Author(s):  
Anna D. Borsodi ◽  
Ralph A. Bradshaw

SummaryThe plasma of individuals, hetero- or homozygous for α1-antitrypsin deficiency, contains greatly decreased amounts of antithrombin activity as assayed against factor Xa. However, heparin stimulation of the residual antithrombin activity is observed, which is comparable to that of normal plasma. Antithrombins isolated from both normal and α1-antitrypsin deficient plasma by a simplified procedure are indistinguishable in both properties and yields. The microheterogeneity observed on isoelectric focusing of both preparations can be eliminated by treatment with neuraminidase. Neither purified human antithrombin nor α1-antitrypsin, when assayed against bovine trypsin, is stimulated by heparin. These results clearly establish the unique natures of antithrombin and α1-antitrypsin and show that about 75% of the antithrombin activity measured in normal plasma is due to α1-antitrypsin. Estimates of anti thrombin III activity in normal plasma by assays dependent on enzymatic activity can probably be obtained only in the presence of heparin.


2011 ◽  
Vol 22 (2) ◽  
pp. 67-74 ◽  
Author(s):  
Malgorzata Sudol ◽  
Jennifer L Fritz ◽  
Melissa Tran ◽  
Gavin P Robertson ◽  
Julie B Ealy ◽  
...  

Background: In addition to activities needed to catalyse integration, retroviral integrases exhibit non-specific endonuclease activity that is enhanced by certain small compounds, suggesting that integrase could be stimulated to damage viral DNA before integration occurs. Methods: A non-radioactive, plate-based, solution phase, fluorescence assay was used to screen a library of 50,080 drug-like chemicals for stimulation of non-specific DNA nicking by HIV-1 integrase. Results: A semi-automated workflow was established and primary hits were readily identified from a graphic output. Overall, 0.6% of the chemicals caused a large increase in fluorescence (the primary hit rate) without also having visible colour that could have artifactually caused this result. None of the potential stimulators from this moderate-size library, however, passed a secondary test that included an inactive integrase mutant that assessed whether the increased fluorescence depended on the endonuclease activity of integrase. Conclusions: This first attempt at identifying integrase stimulator compounds establishes the necessary logistics and workflow required. The results from this study should encourage larger scale high-throughput screening to advance the novel antiviral strategy of stimulating integrase to damage retroviral DNA.


2002 ◽  
Vol 76 (22) ◽  
pp. 11570-11583 ◽  
Author(s):  
Brian R. Lane ◽  
Jianguo Liu ◽  
Paul J. Bock ◽  
Dominique Schols ◽  
Michael J. Coffey ◽  
...  

ABSTRACT The development of the complex neoplasm Kaposi's sarcoma is dependent on infection with the Kaposi's sarcoma-associated herpesvirus (KSHV) and appears to be greatly enhanced by cytokines and human immunodeficiency virus type 1 (HIV-1) Tat. Interleukin-8 (IL-8) and growth-regulated oncogene alpha (GRO-α) are chemokines involved in chemoattraction, neovascularization, and stimulation of HIV-1 replication. We have previously demonstrated that production of GRO-α is stimulated by exposure of monocyte-derived macrophages (MDM) to HIV-1. Here we show that exposure of MDM to HIV-1, viral Tat, or viral gp120 leads to a substantial increase in IL-8 production. We also demonstrate that IL-8 and GRO-α are induced by KSHV infection of endothelial cells and are crucial to the angiogenic phenotype developed by KSHV-infected endothelial cells in cell culture and upon implantation into SCID mice. Thus, the three known etiological factors in Kaposi's sarcoma pathogenesis—KSHV, HIV-1 Tat, and cellular growth factors—might be linked, in part, through induction of IL-8 and GRO-α.


2015 ◽  
Vol 89 (23) ◽  
pp. 12118-12130 ◽  
Author(s):  
Ferdinand Roesch ◽  
Léa Richard ◽  
Réjane Rua ◽  
Françoise Porrot ◽  
Nicoletta Casartelli ◽  
...  

ABSTRACTThe HIV-1 accessory protein Vpr displays different activities potentially impacting viral replication, including the arrest of the cell cycle in the G2phase and the stimulation of apoptosis and DNA damage response pathways. Vpr also modulates cytokine production by infected cells, but this property remains partly characterized. Here, we investigated the effect of Vpr on the production of the proinflammatory cytokine tumor necrosis factor (TNF). We report that Vpr significantly increases TNF secretion by infected lymphocytes.De novoproduction of Vpr is required for this effect. Vpr mutants known to be defective for G2cell cycle arrest induce lower levels of TNF secretion, suggesting a link between these two functions. Silencing experiments and the use of chemical inhibitors further implicated the cellular proteins DDB1 and TAK1 in this activity of Vpr. TNF secreted by HIV-1-infected cells triggers NF-κB activity in bystander cells and allows viral reactivation in a model of latently infected cells. Thus, the stimulation of the proinflammatory pathway by Vpr may impact HIV-1 replicationin vivo.IMPORTANCEThe role of the HIV-1 accessory protein Vpr remains only partially characterized. This protein is important for viral pathogenesis in infected individuals but is dispensable for viral replication in most cell culture systems. Some of the functions described for Vpr remain controversial. In particular, it remains unclear whether Vpr promotes or instead prevents proinflammatory and antiviral immune responses. In this report, we show that Vpr promotes the release of TNF, a proinflammatory cytokine associated with rapid disease progression. Using Vpr mutants or inhibiting selected cellular genes, we show that the cellular proteins DDB1 and TAK1 are involved in the release of TNF by HIV-infected cells. This report provides novel insights into how Vpr manipulates TNF production and helps clarify the role of Vpr in innate immune responses and inflammation.


2018 ◽  
Vol 44 ◽  
pp. 00033 ◽  
Author(s):  
Nina Doskocz ◽  
Katarzyna Affek ◽  
Monika Załęska-Radziwiłł

The increased production and commercial use of nanoparticles (NPs), combined with a lack of regulation regarding their disposal, may result in the unwanted introduction of NPs to wastewater. Wastewater nutrient removal depends on the metabolisms of activated sludge bacteria and their related key enzymes. Therefore, the aim of this work was to determine the effect of aluminium oxide nanoparticles concentrations on the activated sludge enzymatic activity of microorganisms. Tested nanoparticles inhibition cellular respiration in TTC method in the four highest tested concentrations. Moreover, in most samples observed increase dehydrogenase activity. In this study, nano-Al2O3 also caused a clear stimulation of the activity of hydrolytic enzymes microorganisms of activate sludge. Effects of aluminum oxide (compound in bulk forms) on enzymatic activity were different than in the case of the nano from of Al2O3.


2003 ◽  
Vol 124 (4) ◽  
pp. A144
Author(s):  
Paul Rufo ◽  
Patricia W. Lin ◽  
Adriana Andrade ◽  
Charles Flexner ◽  
Lianwei Jiang ◽  
...  

2006 ◽  
Vol 281 (32) ◽  
pp. 22707-22719 ◽  
Author(s):  
Elvire Guiot ◽  
Kevin Carayon ◽  
Olivier Delelis ◽  
Françoise Simon ◽  
Patrick Tauc ◽  
...  
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