scholarly journals Early Steps of Polyomavirus Entry into Cells

2000 ◽  
Vol 74 (18) ◽  
pp. 8582-8588 ◽  
Author(s):  
Joanna M. Gilbert ◽  
Thomas L. Benjamin
Keyword(s):  
Jc Virus ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Dominant Negative ◽  
Independent Manner ◽  
Caveolin 1 ◽  
Dominant Negative Form ◽  
Murine Polyomavirus ◽  
Dynamin I ◽  
Negative Form

ABSTRACT The mechanism by which murine polyomavirus penetrates cells and arrives at the nucleus, the site of viral replication, is not well understood. Simian virus 40 and JC virus, two closely related members of the polyomavirus subfamily, use caveola- and clathrin-mediated uptake pathways for entry, respectively. The data presented here indicate that compounds that block endocytosis of both caveola- and clathrin-derived vesicles have no effect on polyomavirus infectivity. Polyomavirus does not appear to colocalize with either clathrin light chain or caveolin-1 by immunofluorescence microscopy. Additionally, expression of a dominant-negative form of dynamin I has no effect on polyomavirus uptake and infectivity. Therefore, polyomavirus uptake occurs through a class of uncoated vesicles in a clathrin-, caveolin-1-, and dynamin I-independent manner.

scholarly journals Murine Polyomavirus Requires the Endoplasmic Reticulum Protein Derlin-2 To Initiate Infection

2006 ◽  
Vol 80 (17) ◽  
pp. 8739-8744 ◽  
Author(s):  
Brendan N. Lilley ◽  
Joanna M. Gilbert ◽  
Hidde L. Ploegh ◽  
Thomas L. Benjamin
Keyword(s):  
Endoplasmic Reticulum ◽  
Viral Genome ◽  
Cellular Membrane ◽  
Dominant Negative ◽  
Hairpin Rna ◽  
Dominant Negative Form ◽  
Endoplasmic Reticulum Protein ◽  
Murine Polyomavirus ◽  
Infection Inhibition ◽  
Negative Form

ABSTRACT The pathways by which viruses enter cells are diverse, but in all cases, infection necessitates the transfer of the viral genome across a cellular membrane. Polyomavirus (Py) particles, after binding to glycolipid and glycoprotein receptors at the cell surface, are delivered to the lumen of the endoplasmic reticulum (ER). The nature and extent of virus disassembly in the ER, how the viral genome is transported to the cytosol and subsequently to the nucleus, and whether any cellular proteins are involved are not known. Here, we identify an ER-resident protein, Derlin-2, a factor implicated in the removal of misfolded proteins from the ER for cytosolic degradation, as a component of the machinery required for mouse Py to establish an infection. Inhibition of Derlin-2 function by expression of either a dominant-negative form of Derlin-2 or a short hairpin RNA that reduces Derlin-2 levels blocks Py infection by 50 to 75%. The block imposed by Derlin-2 inhibition occurs after the virus reaches the ER and can be bypassed by the introduction of Py DNA into the cytosol. These findings suggest a mode of Py entry that involves cytosolic access via the quality control machinery in the ER.

A dominant negative form of p63 inhibits apoptosis in a p53-independent manner

2006 ◽  
Vol 344 (1) ◽  
pp. 166-172 ◽  
Author(s):  
Hae-ock Lee ◽  
Jung-Hwa Lee ◽  
Eunhee Choi ◽  
Ja Young Seol ◽  
Yungdae Yun ◽  
...  
Keyword(s):  
Dominant Negative ◽  
Independent Manner ◽  
Dominant Negative Form ◽  
Negative Form

scholarly journals Characterization of Rotavirus Cell Entry

2004 ◽  
Vol 78 (5) ◽  
pp. 2310-2318 ◽  
Author(s):  
Claudia Sánchez-San Martín ◽  
Tomás López ◽  
Carlos F. Arias ◽  
Susana López
Keyword(s):  
Dominant Negative ◽  
Cell Entry ◽  
Dominant Negative Mutant ◽  
Cell Infection ◽  
Caveolin 1 ◽  
Dominant Negative Form ◽  
Binding Agents ◽  
Infected Cells ◽  
Negative Form

ABSTRACT While recently we have learned much about the viral and cellular proteins involved in the initial attachment of rotaviruses to MA104 cells, the mechanism by which these viruses reach the interior of the cell is poorly understood. For this study, we observed the effects of drugs and of dominant-negative mutants, known to impair clathrin-mediated endocytosis and endocytosis mediated by caveolae, on rotavirus cell infection. Rotaviruses were able to enter cells in the presence of compounds that inhibit clathrin-mediated endocytosis as well as cells overexpressing a dominant-negative form of Eps15, a protein crucial for the assembly of clathrin coats. We also found that rotaviruses infected cells in which caveolar uptake was blocked; treatment with the cholesterol binding agents nystatin and filipin, as well as transfection of cells with dominant-negative caveolin-1 and caveolin-3 mutants, had no effect on rotavirus infection. Interestingly, cells treated with methyl-β-cyclodextrin, a drug that sequesters cholesterol from membranes, and cells expressing a dominant-negative mutant of the large GTPase dynamin, which is known to function in several membrane scission events, were not infected by rotaviruses, indicating that cholesterol and dynamin play a role in the entry of rotaviruses.

DNA Replication of Chimeric JC Virus-Simian Virus 40 Genomes

Virology ◽  
1994 ◽  
Vol 204 (2) ◽  
pp. 819-822 ◽  
Author(s):  
Kevin J. Lynch ◽  
Sheryl Haggerty ◽  
Richard J. Frisque
Keyword(s):  
Dna Replication ◽  
Jc Virus ◽  
Simian Virus 40 ◽  
Simian Virus

scholarly journals Modulation of flight and feeding behaviours requires presynaptic IP3Rs in dopaminergic neurons

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Anamika Sharma ◽  
Gaiti Hasan
Keyword(s):  
Dopaminergic Neurons ◽  
Calcium Release ◽  
Neural Circuit ◽  
Dominant Negative ◽  
Neuronal Function ◽  
Axonal Projections ◽  
Dominant Negative Form ◽  
Internal States ◽  
Innate Behaviour ◽  
Negative Form

Innate behaviours, although robust and hard wired, rely on modulation of neuronal circuits, for eliciting an appropriate response according to internal states and external cues. Drosophila flight is one such innate behaviour that is modulated by intracellular calcium release through inositol 1,4,5-trisphosphate receptors (IP3Rs). Cellular mechanism(s) by which IP3Rs modulate neuronal function for specific behaviours remain speculative, in vertebrates and invertebrates. To address this, we generated an inducible dominant negative form of the IP3R (IP3RDN). Flies with neuronal expression of IP3RDN exhibit flight deficits. Expression of IP3RDN helped identify key flight-modulating dopaminergic neurons with axonal projections in the mushroom body. Flies with attenuated IP3Rs in these presynaptic dopaminergic neurons exhibit shortened flight bouts and a disinterest in seeking food, accompanied by reduced excitability and dopamine release upon cholinergic stimulation. Our findings suggest that the same neural circuit modulates the drive for food search and for undertaking longer flight bouts.

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