Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway

Tacaribe virus (TCRV) entry occurs by receptor-mediated endocytosis. To explore the entry mechanism used by TCRV, the inhibitory effects of drugs and dominant negative (DN) constructions affecting the main endocytic pathways were analyzed. In cells lacking the human transferrin receptor (hTfR), comp...

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Autores principales: Roldán, J.S., Martínez, M.G., Forlenza, M.B., Whittaker, G.R., Candurra, N.A.
Formato: JOUR
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pH
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_03048608_v161_n2_p353_Roldan
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spelling todo:paper_03048608_v161_n2_p353_Roldan2023-10-03T15:21:01Z Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway Roldán, J.S. Martínez, M.G. Forlenza, M.B. Whittaker, G.R. Candurra, N.A. CD71 antigen cholesterol dynamin leukocyte antigen transferrin receptor animal CHO cell line Cricetulus host pathogen interaction human metabolism New World arenavirus pH physiology virus entry Animals Antigens, CD Arenaviruses, New World CHO Cells Cholesterol Cricetulus Dynamins Host-Pathogen Interactions Humans Hydrogen-Ion Concentration Receptors, Transferrin Virus Internalization Tacaribe virus (TCRV) entry occurs by receptor-mediated endocytosis. To explore the entry mechanism used by TCRV, the inhibitory effects of drugs and dominant negative (DN) constructions affecting the main endocytic pathways were analyzed. In cells lacking the human transferrin receptor (hTfR), compounds and DN proteins that impair clathrin-mediated endocytosis were shown to reduce virus internalization without affecting virion binding. In contrast, in cells expressing the hTfR, compounds that affect clathrin-mediated endocytosis did not affect TCRV infection. Destabilization of cholesterol-rich plasma membrane microdomains by treatment with nystatin was not able to block virus entry in the presence of hTfR. However methyl-β-cyclodextrin, which extracts cholesterol from cell membranes, reduced virus internalization in cells expressing the hTfR. Inhibition of dynamin and neutralization of the pH of intracellular vesicles reduced virus internalization in all cell lines tested. Taken together, these results demonstrate that in cells expressing the hTfR, TCRV internalization depends on the presence of cholesterol, dynamin and acidic intracellular vesicles, while in the rest of the cell lines analyzed, clathrin-mediated endocytosis is the main TCRV entry pathway and, as expected, depends on dynamin and acidic intracellular vesicles. These results represent an important contribution to the characterization of the arenavirus replication cycle. © 2015, Springer-Verlag Wien. Fil:Martínez, M.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Forlenza, M.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Candurra, N.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03048608_v161_n2_p353_Roldan
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic CD71 antigen
cholesterol
dynamin
leukocyte antigen
transferrin receptor
animal
CHO cell line
Cricetulus
host pathogen interaction
human
metabolism
New World arenavirus
pH
physiology
virus entry
Animals
Antigens, CD
Arenaviruses, New World
CHO Cells
Cholesterol
Cricetulus
Dynamins
Host-Pathogen Interactions
Humans
Hydrogen-Ion Concentration
Receptors, Transferrin
Virus Internalization
spellingShingle CD71 antigen
cholesterol
dynamin
leukocyte antigen
transferrin receptor
animal
CHO cell line
Cricetulus
host pathogen interaction
human
metabolism
New World arenavirus
pH
physiology
virus entry
Animals
Antigens, CD
Arenaviruses, New World
CHO Cells
Cholesterol
Cricetulus
Dynamins
Host-Pathogen Interactions
Humans
Hydrogen-Ion Concentration
Receptors, Transferrin
Virus Internalization
Roldán, J.S.
Martínez, M.G.
Forlenza, M.B.
Whittaker, G.R.
Candurra, N.A.
Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway
topic_facet CD71 antigen
cholesterol
dynamin
leukocyte antigen
transferrin receptor
animal
CHO cell line
Cricetulus
host pathogen interaction
human
metabolism
New World arenavirus
pH
physiology
virus entry
Animals
Antigens, CD
Arenaviruses, New World
CHO Cells
Cholesterol
Cricetulus
Dynamins
Host-Pathogen Interactions
Humans
Hydrogen-Ion Concentration
Receptors, Transferrin
Virus Internalization
description Tacaribe virus (TCRV) entry occurs by receptor-mediated endocytosis. To explore the entry mechanism used by TCRV, the inhibitory effects of drugs and dominant negative (DN) constructions affecting the main endocytic pathways were analyzed. In cells lacking the human transferrin receptor (hTfR), compounds and DN proteins that impair clathrin-mediated endocytosis were shown to reduce virus internalization without affecting virion binding. In contrast, in cells expressing the hTfR, compounds that affect clathrin-mediated endocytosis did not affect TCRV infection. Destabilization of cholesterol-rich plasma membrane microdomains by treatment with nystatin was not able to block virus entry in the presence of hTfR. However methyl-β-cyclodextrin, which extracts cholesterol from cell membranes, reduced virus internalization in cells expressing the hTfR. Inhibition of dynamin and neutralization of the pH of intracellular vesicles reduced virus internalization in all cell lines tested. Taken together, these results demonstrate that in cells expressing the hTfR, TCRV internalization depends on the presence of cholesterol, dynamin and acidic intracellular vesicles, while in the rest of the cell lines analyzed, clathrin-mediated endocytosis is the main TCRV entry pathway and, as expected, depends on dynamin and acidic intracellular vesicles. These results represent an important contribution to the characterization of the arenavirus replication cycle. © 2015, Springer-Verlag Wien.
format JOUR
author Roldán, J.S.
Martínez, M.G.
Forlenza, M.B.
Whittaker, G.R.
Candurra, N.A.
author_facet Roldán, J.S.
Martínez, M.G.
Forlenza, M.B.
Whittaker, G.R.
Candurra, N.A.
author_sort Roldán, J.S.
title Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway
title_short Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway
title_full Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway
title_fullStr Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway
title_full_unstemmed Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway
title_sort human transferrin receptor triggers an alternative tacaribe virus internalization pathway
url http://hdl.handle.net/20.500.12110/paper_03048608_v161_n2_p353_Roldan
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AT whittakergr humantransferrinreceptortriggersanalternativetacaribevirusinternalizationpathway
AT candurrana humantransferrinreceptortriggersanalternativetacaribevirusinternalizationpathway
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