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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Detalles Bibliográficos
Autores principales: Roldán, J.S., Martínez, M.G., Forlenza, M.B., Whittaker, G.R., Candurra, N.A.
Formato: JOUR
Materias:
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
Dynamins
Host-Pathogen Interactions
Humans
Hydrogen-Ion Concentration
Receptors, Transferrin
Virus Internalization
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_03048608_v161_n2_p353_Roldan
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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.

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