The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
Mary K. Estes - One of the best experts on this subject based on the ideXlab platform.
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secretory pathway antagonism by calicivirus homologues of norwalk virus nonstructural Protein P22 is restricted to noroviruses
Virology Journal, 2012Co-Authors: Tyler M Sharp, Sue E Crawford, Kazuhiko Katayama, Nadim J Ajami, Frederick H Neill, Robert L Atmar, Budi Utama, Mary K. EstesAbstract:Our previous report that the Norwalk virus nonstructural Protein P22 is an antagonist of the cellular secretory pathway suggests a new aspect of norovirus/host interaction. To explore conservation of function of this highly divergent calicivirus Protein, we examined the effects of P22 homologues from four human and two murine noroviruses, and feline calicivirus on the secretory pathway. All human noroviruses examined induced Golgi disruption and inhibited Protein secretion, with the genogroup II.4 Houston virus being the most potent antagonist. Genogroup II.6 viruses have a conserved mutation in the mimic of an Endoplasmic Reticulum export signal (MERES) motif that is highly conserved in human norovirus homologues of P22 and is critical for secretory pathway antagonism, and these viruses had reduced levels of Golgi disruption and inhibition of Protein secretion. P22 homologues from both persistent and nonpersistent strains of murine norovirus induced Golgi disruption, but only mildly inhibited cellular Protein secretion. Feline calicivirus p30 did not induce Golgi disruption or inhibit cellular Protein secretion. These differences confirm a norovirus-specific effect on host cell secretory pathway antagonism by homologues of P22, which may affect viral replication and/or cellular pathogenesis.
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inhibition of cellular Protein secretion by norwalk virus nonstructural Protein P22 requires a mimic of an endoplasmic reticulum export signal
PLOS ONE, 2010Co-Authors: Tyler M Sharp, Susana Guix, Sue E Crawford, Kazuhiko Katayama, Mary K. EstesAbstract:Protein trafficking between the endoplasmic reticulum (ER) and Golgi apparatus is central to cellular homeostasis. ER export signals are utilized by a subset of Proteins to rapidly exit the ER by direct uptake into COPII vesicles for transport to the Golgi. Norwalk virus nonstructural Protein P22 contains a YXΦESDG motif that mimics a di-acidic ER export signal in both sequence and function. However, unlike normal ER export signals, the ER export signal mimic of P22 is necessary for apparent inhibition of normal COPII vesicle trafficking, which leads to Golgi disassembly and antagonism of Golgi-dependent cellular Protein secretion. This is the first reported function for P22. Disassembly of the Golgi apparatus was also observed in cells replicating Norwalk virus, which may contribute to pathogenesis by interfering with cellular processes that are dependent on an intact secretory pathway. These results indicate that the ER export signal mimic is critical to the antagonistic function of P22, shown herein to be a novel antagonist of ER/Golgi trafficking. This unique and well-conserved human norovirus motif is therefore an appealing target for antiviral drug development.
Tyler M Sharp - One of the best experts on this subject based on the ideXlab platform.
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secretory pathway antagonism by calicivirus homologues of norwalk virus nonstructural Protein P22 is restricted to noroviruses
Virology Journal, 2012Co-Authors: Tyler M Sharp, Sue E Crawford, Kazuhiko Katayama, Nadim J Ajami, Frederick H Neill, Robert L Atmar, Budi Utama, Mary K. EstesAbstract:Our previous report that the Norwalk virus nonstructural Protein P22 is an antagonist of the cellular secretory pathway suggests a new aspect of norovirus/host interaction. To explore conservation of function of this highly divergent calicivirus Protein, we examined the effects of P22 homologues from four human and two murine noroviruses, and feline calicivirus on the secretory pathway. All human noroviruses examined induced Golgi disruption and inhibited Protein secretion, with the genogroup II.4 Houston virus being the most potent antagonist. Genogroup II.6 viruses have a conserved mutation in the mimic of an Endoplasmic Reticulum export signal (MERES) motif that is highly conserved in human norovirus homologues of P22 and is critical for secretory pathway antagonism, and these viruses had reduced levels of Golgi disruption and inhibition of Protein secretion. P22 homologues from both persistent and nonpersistent strains of murine norovirus induced Golgi disruption, but only mildly inhibited cellular Protein secretion. Feline calicivirus p30 did not induce Golgi disruption or inhibit cellular Protein secretion. These differences confirm a norovirus-specific effect on host cell secretory pathway antagonism by homologues of P22, which may affect viral replication and/or cellular pathogenesis.
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inhibition of cellular Protein secretion by norwalk virus nonstructural Protein P22 requires a mimic of an endoplasmic reticulum export signal
PLOS ONE, 2010Co-Authors: Tyler M Sharp, Susana Guix, Sue E Crawford, Kazuhiko Katayama, Mary K. EstesAbstract:Protein trafficking between the endoplasmic reticulum (ER) and Golgi apparatus is central to cellular homeostasis. ER export signals are utilized by a subset of Proteins to rapidly exit the ER by direct uptake into COPII vesicles for transport to the Golgi. Norwalk virus nonstructural Protein P22 contains a YXΦESDG motif that mimics a di-acidic ER export signal in both sequence and function. However, unlike normal ER export signals, the ER export signal mimic of P22 is necessary for apparent inhibition of normal COPII vesicle trafficking, which leads to Golgi disassembly and antagonism of Golgi-dependent cellular Protein secretion. This is the first reported function for P22. Disassembly of the Golgi apparatus was also observed in cells replicating Norwalk virus, which may contribute to pathogenesis by interfering with cellular processes that are dependent on an intact secretory pathway. These results indicate that the ER export signal mimic is critical to the antagonistic function of P22, shown herein to be a novel antagonist of ER/Golgi trafficking. This unique and well-conserved human norovirus motif is therefore an appealing target for antiviral drug development.
Jeanmichel Rossignol - One of the best experts on this subject based on the ideXlab platform.
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The Hepatitis B Virus Precore Protein Is Retrotransported from Endoplasmic Reticulum (ER) to Cytosol through the ER-associated Degradation Pathway
Journal of Biological Chemistry, 2008Co-Authors: Marion Duriez, Jeanmichel Rossignol, Delphine SitterlinAbstract:Abstract The hepatitis B virus precore Protein is closely related to the nucleocapsid core Protein but is processed distinctly in the cell and plays a different role in the viral cycle. Precore is addressed to the endoplasmic reticulum (ER) through a signal peptide, and the form present in the ER is the P22 Protein. P22 is then cleaved in its C-terminal part to be secreted as HBe antigen. In addition, a cytosolic form of 22 kDa less characterized has been observed. Precore gene was shown to be implicated in viral persistence, but until now, the actual Protein species involved has not been determined. Our work focuses on the cytosolic form of precore. Using human cells expressing precore and a convenient fractionation assay, we demonstrated that the cytosolic form is identical to the ER form and retrotransported in the cytoplasm through the ER-associated degradation pathway. This cellular machinery translocates misfolded Proteins to the cytoplasm, where they are ubiquitinated on lysine residues and degraded by proteasome. We showed that precore escapes proteasome due to its low lysine content and accumulates in the cytosol. The role of this retrotransport was investigated. In the presence of precore, we found a specific redistribution of the Grp78/BiP chaperone Protein to cytosol and demonstrated a specific interaction between precore and Grp78/BiP. Altogether, these data support the idea that the hepatitis B virus develops a strategy to take advantage of the ER-associated degradation pathway, allowing distinct subcellular localization and probably distinct roles for the viral precore Protein.
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in vitro and in vivo interactions between the hepatitis b virus Protein P22 and the cellular Protein gc1qr
Journal of Virology, 2003Co-Authors: S Laine, A Thouard, J Derancourt, M Kress, D Sitterlin, Jeanmichel RossignolAbstract:gC1qR, a mitochondrial matrix Protein, was identified as the main cellular partner of the hepatitis B virus P22 Protein. We demonstrated by immunofluorescence studies that some P22 molecules were colocalized with the endogenous gC1qR in both the cytoplasm and the nucleus but never in the mitochondria. We also showed that the last 34 amino acids of P22 were involved in the association with gC1qR.
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The C Terminus of the Hepatitis B Virus e Antigen Precursor Is Required for a Tunicamycin-sensitive Step That Promotes Efficient Secretion of the Antigen
Journal of Biological Chemistry, 1998Co-Authors: Fabienne Messageot, Damien Carlier, Jeanmichel RossignolAbstract:Abstract The Hepatitis B virus encodes the secreted e antigen (HBe) whose function in the viral life cycle is unknown. HBe derives from a 25-kDa precursor that is directed to the secretory pathway. After cleavage of the signal sequence, the resulting 22-kDa Protein (P22) is processed in a post-endoplasmic reticulum compartment to mature HBe by removal of the 34-amino acid C-terminal domain. The efficiency of HBe secretion is specifically decreased in cells grown in the presence of tunicamycin, an inhibitor ofN-glycosylation. Inasmuch as HBe precursor is notN-glycosylated, our data suggest that a cellular tunicamycin-sensitive Protein increases the intracellular transport through the HBe secretory pathway. The study of the secretion of HBe derived from C-terminal-truncated precursors demonstrates that the tunicamycin-sensitive secretion absolutely requires a part of the C-terminal region that is removed to form mature HBe, indicating that the cellular tunicamycin-sensitive Protein increases the efficiency of the intracellular transport of P22. We have also shown that theEscherichia coli β-galactosidase can be secreted when fused to the HBe precursor signal sequence and that the P22 C-terminal domain renders the secretion of this reporter Protein also tunicamycin-sensitive.
Kazuhiko Katayama - One of the best experts on this subject based on the ideXlab platform.
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secretory pathway antagonism by calicivirus homologues of norwalk virus nonstructural Protein P22 is restricted to noroviruses
Virology Journal, 2012Co-Authors: Tyler M Sharp, Sue E Crawford, Kazuhiko Katayama, Nadim J Ajami, Frederick H Neill, Robert L Atmar, Budi Utama, Mary K. EstesAbstract:Our previous report that the Norwalk virus nonstructural Protein P22 is an antagonist of the cellular secretory pathway suggests a new aspect of norovirus/host interaction. To explore conservation of function of this highly divergent calicivirus Protein, we examined the effects of P22 homologues from four human and two murine noroviruses, and feline calicivirus on the secretory pathway. All human noroviruses examined induced Golgi disruption and inhibited Protein secretion, with the genogroup II.4 Houston virus being the most potent antagonist. Genogroup II.6 viruses have a conserved mutation in the mimic of an Endoplasmic Reticulum export signal (MERES) motif that is highly conserved in human norovirus homologues of P22 and is critical for secretory pathway antagonism, and these viruses had reduced levels of Golgi disruption and inhibition of Protein secretion. P22 homologues from both persistent and nonpersistent strains of murine norovirus induced Golgi disruption, but only mildly inhibited cellular Protein secretion. Feline calicivirus p30 did not induce Golgi disruption or inhibit cellular Protein secretion. These differences confirm a norovirus-specific effect on host cell secretory pathway antagonism by homologues of P22, which may affect viral replication and/or cellular pathogenesis.
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inhibition of cellular Protein secretion by norwalk virus nonstructural Protein P22 requires a mimic of an endoplasmic reticulum export signal
PLOS ONE, 2010Co-Authors: Tyler M Sharp, Susana Guix, Sue E Crawford, Kazuhiko Katayama, Mary K. EstesAbstract:Protein trafficking between the endoplasmic reticulum (ER) and Golgi apparatus is central to cellular homeostasis. ER export signals are utilized by a subset of Proteins to rapidly exit the ER by direct uptake into COPII vesicles for transport to the Golgi. Norwalk virus nonstructural Protein P22 contains a YXΦESDG motif that mimics a di-acidic ER export signal in both sequence and function. However, unlike normal ER export signals, the ER export signal mimic of P22 is necessary for apparent inhibition of normal COPII vesicle trafficking, which leads to Golgi disassembly and antagonism of Golgi-dependent cellular Protein secretion. This is the first reported function for P22. Disassembly of the Golgi apparatus was also observed in cells replicating Norwalk virus, which may contribute to pathogenesis by interfering with cellular processes that are dependent on an intact secretory pathway. These results indicate that the ER export signal mimic is critical to the antagonistic function of P22, shown herein to be a novel antagonist of ER/Golgi trafficking. This unique and well-conserved human norovirus motif is therefore an appealing target for antiviral drug development.
Eladio Vinuela - One of the best experts on this subject based on the ideXlab platform.
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Protein P22 of african swine fever virus an early structural Protein that is incorporated into the membrane of infected cells
Virology, 1991Co-Authors: Ana Camacho, Eladio VinuelaAbstract:Abstract The open reading frame K'177, located at the left end of the African swine fever virus genome, codes for an early induced structural Protein of 22,000 Da (P22), which is released from the viral particle by the nonionic detergent n -octyl-β- d -glucopyranoside under conditions that solubilize external viral structural Proteins. The predicted amino acid sequence of the Protein contains a hydrophobic region at its N-terminus with characteristics of a signal peptide and, at early times after virus infection of Vero cells, the Protein can be detected in the cell membrane by immunolabeling.
