Alternative infectious entry pathways for dengue virus serotypes into mammalian cells

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Dengue virus (DENV) poses a significant global health threat.
• Understanding DENV entry mechanisms is crucial for developing antiviral strategies.
• Previous studies indicated varied entry pathways for different DENV serotypes.

Purpose of the Study:

• To elucidate the distinct entry mechanisms of DENV-1 and DENV-2 into Vero cells.
• To investigate the role of endocytic pathways in DENV internalization.
• To compare DENV entry pathways across different cell types.

Main Methods:

• Biochemical inhibitors and dominant-negative mutants were used to probe endocytic pathways.
• Fluorescence microscopy and infectivity assays quantified viral entry.
• Specific inhibitors (e.g., dansylcadaverine, chlorpromazine, dynasore) and genetic manipulations (e.g., Eps15, caveolin-1, dynamin mutants) were employed.

Main Results:

• DENV-1 internalization into Vero cells is clathrin-mediated.
• DENV-2 entry into Vero cells is independent of clathrin, caveolae, and lipid rafts but requires dynamin.
• DENV-2 entry into A549 cells is clathrin-dependent, contrasting with its entry into Vero cells.

Conclusions:

• DENV-1 and DENV-2 exhibit differential infectious entry mechanisms into Vero cells.
• DENV-2 utilizes alternative, non-classical endocytic pathways depending on the host cell type.
• These findings highlight the complexity of DENV host-cell interactions and offer targets for therapeutic intervention.