Autophagy-Associated Proteins Control Ebola Virus Internalization Into Host Cells
Olena Shtanko1, Ann N Reyes1, William T Jackson2
1Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio.
Abstract:
Ebola virus (EBOV) enters host cells by macropinocytosis, a poorly understood process. Recent studies have suggested that cell factors involved in autophagy, an evolutionally conserved pathway leading to the lysosomal degradation of protein aggregates and organelles during cellular stress, also have roles in macropinocytosis. Here, we demonstrate that autophagy-associated proteins are required for trafficking of EBOV into the cell body. Depleting cells of beclin 1, autophagy-related protein 7, or microtubule-associated protein 1A/B light chain 3B (LC3B) abolished EBOV uptake, owing to a block in vesicle formation at the cell surface. Both LC3B-I and LC3B-II interacted with macropinocytic structures. Our work indicates that, although various forms of LC3B possess an inherent ability to associate with forming macropinosomes, LC3B-II is critical for internalization of macropinocytic vesicles and, therefore, EBOV from the cell surface.
Insights
Autophagy proteins are crucial for Ebola virus (EBOV) entry into host cells. Microtubule-associated protein 1A/B light chain 3B (LC3B)-II specifically mediates EBOV-containing vesicle internalization.
Area of Science:
- Cell Biology
- Virology
- Molecular Biology
Background:
- Ebola virus (EBOV) entry into host cells occurs via macropinocytosis, a cellular process not fully understood.
- Autophagy, a cellular degradation pathway, shares components with macropinocytosis, suggesting a potential role in viral entry.
Purpose of the Study:
- To investigate the role of autophagy-associated proteins in EBOV macropinocytosis.
- To determine the specific contribution of microtubule-associated protein 1A/B light chain 3B (LC3B) in EBOV uptake.
Main Methods:
- Depletion of autophagy-associated proteins (beclin 1, ATG7, LC3B) in host cells.
- Assessment of EBOV uptake and macropinocytic vesicle formation.
- Analysis of LC3B-I and LC3B-II interaction with macropinocytic structures.
Main Results:
- Depletion of beclin 1, ATG7, or LC3B significantly inhibited EBOV uptake.
- Autophagy protein depletion blocked macropinocytic vesicle formation at the cell surface.
- LC3B-II was identified as critical for the internalization of macropinocytic vesicles containing EBOV.
Conclusions:
- Autophagy-associated proteins are essential for EBOV trafficking and cellular entry.
- LC3B-II plays a critical role in the internalization of macropinosomes, facilitating EBOV infection.
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