Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway

Julieta S. Roldán, María G. Martínez, María B. Forlenza, Gary R. Whittaker, Nélida A. Candurra

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)353-363
Number of pages11
JournalArchives of Virology
Volume161
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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ASJC Scopus subject areas

  • Virology
  • Medicine(all)

Cite this

Roldán, J. S., Martínez, M. G., Forlenza, M. B., Whittaker, G. R., & Candurra, N. A. (2016). Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway. Archives of Virology, 161(2), 353-363. https://doi.org/10.1007/s00705-015-2652-3