Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Tacaribe virus (TCRV) is an arenavirus known to enter cells via receptor-mediated endocytosis.
• Understanding viral entry mechanisms is crucial for developing antiviral strategies.

Purpose of the Study:

• To elucidate the specific endocytic pathways utilized by TCRV for cell entry.
• To investigate the role of the human transferrin receptor (hTfR) in TCRV internalization.

Main Methods:

• Analysis of TCRV internalization using inhibitory drugs and dominant-negative (DN) constructs targeting endocytic pathways.
• Experiments conducted in cell lines with and without the human transferrin receptor (hTfR).
• Assessment of viral binding, internalization, and infection under various experimental conditions.

Main Results:

• In cells lacking hTfR, clathrin-mediated endocytosis was the primary pathway for TCRV internalization.
• In cells expressing hTfR, TCRV entry was independent of clathrin-mediated endocytosis but dependent on cholesterol, dynamin, and acidic intracellular vesicles.
• Methyl-β-cyclodextrin treatment reduced TCRV internalization in hTfR-expressing cells, indicating cholesterol's role.

Conclusions:

• TCRV employs distinct entry mechanisms based on the presence of hTfR.
• The findings contribute to a deeper understanding of arenavirus replication and host cell interactions.