The Experts below are selected from a list of 6951 Experts worldwide ranked by ideXlab platform
Christine Tuffereau - One of the best experts on this subject based on the ideXlab platform.
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The Rabies Virus Glycoprotein Receptor p75NTR Is Not Essential for Rabies Virus Infection
Journal of virology, 2007Co-Authors: Christine Tuffereau, Kh Schmidt, Christelle Langevin, Florence Lafay, Georg Dechant, Martin KoltzenburgAbstract:Rabies virus glycoprotein (RvG) is known to be the only factor that mediates rabies infection. The neurotrophin receptor (p75NTR), through its cysteine-rich domain 1, is a specific receptor for RvG and neutralizes virus infectivity, but its role in virus infection has remained obscure. We used adult mouse dorsal root ganglion (DRG) neurons as a model to study the role of p75NTR in Rv infection of primary neurons. We show that Rv infects around 20% of DRG neurons, of which more than 80% are p75NTR positive, have large diameters, and are capsaicin insensitive. Surprisingly, Rv binding and infection are absent in about half of the p75NTR-expressing DRG neurons which have small diameters and are often capsaicin sensitive. This indicates that p75NTR is not sufficient to mediate Rv interaction in sensory neurons. The rate and specificity of neural infection are unchanged in Rv-infected p75NTRExonIV−/− mice that lack all extracellular receptor domains and in wild-type mice infected with two Independent Rv mutants that lack p75NTR binding. Accordingly, the mortality rate is unchanged in the absence of Rv-p75NTR interaction. We conclude that although p75NTR is a receptor for soluble RvG in transfected cells of heterologous expression systems, an RvG-p75NTR interaction is not necessary for Rv infection of primary neurons. This means that other receptors are required to mediate Rv infection in vivo and in vitro.
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Mutations Conferring Resistance to Neutralization by a Soluble Form of the Neurotrophin Receptor (p75NTR) Map outside of the Known Antigenic Sites of the Rabies Virus Glycoprotein
Journal of virology, 2002Co-Authors: Christelle Langevin, Christine TuffereauAbstract:The neurotrophin receptor (p75NTR) seRves as a receptor for rabies virus (Rv). We expressed and purified a soluble chimera consisting of the p75NTR ectodomain fused to the human immunoglobulin G1 (IgG1) Fc fragment (p75-Fc). Although p75-Fc interacts with Rv, the infectivity of Rv did not decrease significantly when it was incubated in the presence of the soluble receptor alone. However, when it was subsequently incubated with an antihuman IgG directed against the Fc fragment of p75-Fc, the infectivity of Rv was significantly lowered (>90%), whereas incubation with antihuman IgG alone had no effect. We then selected eight Independent Rv mutants that were not neutralized by p75-Fc and antihuman IgG (srr [soluble receptor resistant] mutants). Each mutant carried a single mutation in the glycoprotein gene leading to one amino acid substitution in the protein. A total of four different substitutions were found. Two of the mutations were located at position 318 (phenylalanine replaced by a serine or a valine residue), and two were located at position 352 (histidine replaced by a tyrosine or an arginine residue). All of the mutations prevented the interaction with p75NTR as either a soluble or a membrane-anchored form. Two mutants (F318S) and (H352R) resulted in the formation of small plaques on BSR cells, probably due to the slower maturation of the glycoprotein. Immunoprecipitation, immunofluorescence, and neutralization assays showed that the four mutated glycoproteins still interacted with representative anti-Rv glycoprotein monoclonal antibodies (MAbs), indicating that p75NTR binds outside of the known Rv glycoprotein antigenic sites.
Christelle Langevin - One of the best experts on this subject based on the ideXlab platform.
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The Rabies Virus Glycoprotein Receptor p75NTR Is Not Essential for Rabies Virus Infection
Journal of virology, 2007Co-Authors: Christine Tuffereau, Kh Schmidt, Christelle Langevin, Florence Lafay, Georg Dechant, Martin KoltzenburgAbstract:Rabies virus glycoprotein (RvG) is known to be the only factor that mediates rabies infection. The neurotrophin receptor (p75NTR), through its cysteine-rich domain 1, is a specific receptor for RvG and neutralizes virus infectivity, but its role in virus infection has remained obscure. We used adult mouse dorsal root ganglion (DRG) neurons as a model to study the role of p75NTR in Rv infection of primary neurons. We show that Rv infects around 20% of DRG neurons, of which more than 80% are p75NTR positive, have large diameters, and are capsaicin insensitive. Surprisingly, Rv binding and infection are absent in about half of the p75NTR-expressing DRG neurons which have small diameters and are often capsaicin sensitive. This indicates that p75NTR is not sufficient to mediate Rv interaction in sensory neurons. The rate and specificity of neural infection are unchanged in Rv-infected p75NTRExonIV−/− mice that lack all extracellular receptor domains and in wild-type mice infected with two Independent Rv mutants that lack p75NTR binding. Accordingly, the mortality rate is unchanged in the absence of Rv-p75NTR interaction. We conclude that although p75NTR is a receptor for soluble RvG in transfected cells of heterologous expression systems, an RvG-p75NTR interaction is not necessary for Rv infection of primary neurons. This means that other receptors are required to mediate Rv infection in vivo and in vitro.
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Mutations Conferring Resistance to Neutralization by a Soluble Form of the Neurotrophin Receptor (p75NTR) Map outside of the Known Antigenic Sites of the Rabies Virus Glycoprotein
Journal of virology, 2002Co-Authors: Christelle Langevin, Christine TuffereauAbstract:The neurotrophin receptor (p75NTR) seRves as a receptor for rabies virus (Rv). We expressed and purified a soluble chimera consisting of the p75NTR ectodomain fused to the human immunoglobulin G1 (IgG1) Fc fragment (p75-Fc). Although p75-Fc interacts with Rv, the infectivity of Rv did not decrease significantly when it was incubated in the presence of the soluble receptor alone. However, when it was subsequently incubated with an antihuman IgG directed against the Fc fragment of p75-Fc, the infectivity of Rv was significantly lowered (>90%), whereas incubation with antihuman IgG alone had no effect. We then selected eight Independent Rv mutants that were not neutralized by p75-Fc and antihuman IgG (srr [soluble receptor resistant] mutants). Each mutant carried a single mutation in the glycoprotein gene leading to one amino acid substitution in the protein. A total of four different substitutions were found. Two of the mutations were located at position 318 (phenylalanine replaced by a serine or a valine residue), and two were located at position 352 (histidine replaced by a tyrosine or an arginine residue). All of the mutations prevented the interaction with p75NTR as either a soluble or a membrane-anchored form. Two mutants (F318S) and (H352R) resulted in the formation of small plaques on BSR cells, probably due to the slower maturation of the glycoprotein. Immunoprecipitation, immunofluorescence, and neutralization assays showed that the four mutated glycoproteins still interacted with representative anti-Rv glycoprotein monoclonal antibodies (MAbs), indicating that p75NTR binds outside of the known Rv glycoprotein antigenic sites.
Martin Koltzenburg - One of the best experts on this subject based on the ideXlab platform.
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The Rabies Virus Glycoprotein Receptor p75NTR Is Not Essential for Rabies Virus Infection
Journal of virology, 2007Co-Authors: Christine Tuffereau, Kh Schmidt, Christelle Langevin, Florence Lafay, Georg Dechant, Martin KoltzenburgAbstract:Rabies virus glycoprotein (RvG) is known to be the only factor that mediates rabies infection. The neurotrophin receptor (p75NTR), through its cysteine-rich domain 1, is a specific receptor for RvG and neutralizes virus infectivity, but its role in virus infection has remained obscure. We used adult mouse dorsal root ganglion (DRG) neurons as a model to study the role of p75NTR in Rv infection of primary neurons. We show that Rv infects around 20% of DRG neurons, of which more than 80% are p75NTR positive, have large diameters, and are capsaicin insensitive. Surprisingly, Rv binding and infection are absent in about half of the p75NTR-expressing DRG neurons which have small diameters and are often capsaicin sensitive. This indicates that p75NTR is not sufficient to mediate Rv interaction in sensory neurons. The rate and specificity of neural infection are unchanged in Rv-infected p75NTRExonIV−/− mice that lack all extracellular receptor domains and in wild-type mice infected with two Independent Rv mutants that lack p75NTR binding. Accordingly, the mortality rate is unchanged in the absence of Rv-p75NTR interaction. We conclude that although p75NTR is a receptor for soluble RvG in transfected cells of heterologous expression systems, an RvG-p75NTR interaction is not necessary for Rv infection of primary neurons. This means that other receptors are required to mediate Rv infection in vivo and in vitro.
A. Vonk Noordegraaf - One of the best experts on this subject based on the ideXlab platform.
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The effect of treatment on right ventriculo-arterial coupling in idiopathic pulmonary arterial hypertension
European Respiratory Journal, 2013Co-Authors: C.e.e. Van Der Bruggen, Pia Trip, F.s. De Man, Herman J. Bogaard, Nico Westerhof, A. Vonk NoordegraafAbstract:Introduction: Right heart failure is the main cause of death in idiopathic pulmonary arterial hypertension (IPAH). Current medication aims to reduce right ventricular (Rv) afterload, but the effect on Rv function is unknown. Therefore, we aimed to assess the influence of PAH-specific treatment on load-Independent Rv systolic function and Rv-arterial coupling. Methods: In 39 IPAH patients we determined Rv end-systolic elastance (Ees), arterial elastance (Ea) and Rv-arterial coupling (Ees/Ea) at baseline and follow-up. Maximal isovolumic pressure (Piso) was estimated from Rv pressure cuRves with the single-beat method. Ees=(Piso-mPAP)/SV and Ea=mPAP/SV. (SV=stroke volume, mPAP=mean pulmonary artery pressure, both measured using right heart catheterization) Results: Median follow-up (FU) time was 0.8 years (interquartile range 0.5-1.0). PAH-therapy lowers mPAP, pulmonary vascular resistance and mean right atrial pressure and increases cardiac index (p
Vojtech Melenovsky - One of the best experts on this subject based on the ideXlab platform.
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ACUTE UNLOADING EFFECTS OF SILDENAFIL ENHANCE RIGHT VENTRICULAR-PULMONARY ARTERY COUPLING IN HEART FAILURE.
Journal of cardiac failure, 2020Co-Authors: Luca Monzo, Adrian Reichenbach, Hikmet Al-hiti, Barry A Borlaug, Tereza Havlenova, Nevenka Solar, Marek Tupy, Jiri Ters, Josef Kautzner, Vojtech MelenovskyAbstract:Phosphodiesterase-5A inhibitors (PDE5i) are sometimes used in patients with advanced HFrEF prior to heart transplant or LVAD to reduce Rv afterload and mitigate the risk of right HF. Conflicting evidences exist regarding the impact of these drugs on right ventricular (Rv) contractility. The aim of the study was to explore the acute effects of PDE5i on ventricular-vascular coupling and load-Independent Rv contractility. 22 patients underwent right heart catheterization (RHC) and gated equilibrium blood pool SPECT, before and after 20-mg intravenous sildenafil. SPECT and RHC-derived data were used to calculate Rv loading and contractility. PDE5i induced a reduction in RA pressure (-43%), pulmonary artery (PA) mean pressure (-26%) and wedge pressure (PAWP; -23%), with favorable reductions in PVR (-41%) and PA elastance (Ea; -40%), and increased cardiac output (+13%) (all p<0.01). Rv ejection fraction increased with sildenafil (RvEF; +20%), with no change of Rv contractility (Rv Eessb, p=0.74), indicating that the improvement in RvEF was related to enhanced Rv-PA coupling (r=0.59, p=0.004) by reduction of ventricular load. Rv diastolic compliance (dV/dP) increased with sildenafil. The reduction in PAWP correlated with Rv EDV reduction, while no relationship was obseRved with the change in LV transmural pressure, suggesting decreased pericardial constraint. Acute PDE5i administration has profound Rv afterload-reducing effects, improves Rv EF, reduces Rv volumes and lowers PAWP predominantly through relief of pericardial constraint, without effects on Rv chamber contractility. These findings support further study of PDE5i in protection of Rv function in advanced HFrEF who are at risk of Rv failure. Copyright © 2020. Published by Elsevier Inc.
