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Real-Time, Semi-Automated Fluorescent Measurement of the Airway Surface Liquid pH of Primary Human Airway Epithelial Cells
Published on: June 13, 2019
Macropinocytosis contributes to hantavirus entry into human airway epithelial cells
Giulia Torriani1, Jennifer Mayor2, Gert Zimmer3
1Institute of Microbiology, University Hospital Center and University of Lausanne, Rue du Bugnon 48, CH-1011 Lausanne, Switzerland.
Abstract:
Hantaviruses are emerging rodent-borne negative-strand RNA viruses associated with severe human diseases. Zoonotic transmission occurs via aerosols of contaminated rodent excreta and cells of the human respiratory epithelium represent likely early targets. Here we investigated cellular factors involved in entry of the pathogenic Old and New World hantaviruses Hantaan virus (HTNV) and Andes virus (ANDV) into human respiratory epithelial cells. Screening of a kinase inhibitor library using a biocontained recombinant vesicular stomatitis virus pseudotype platform revealed differential requirement for host kinases for HTNV and ANDV entry and provided first hints for an involvement of macropinocytosis. Examination of a selected panel of well-defined inhibitors of endocytosis confirmed that both HTNV and ANDV enter human respiratory epithelial cells via a pathway that critically depends on sodium proton exchangers and actin, hallmarks of macropinocytosis. However, HTNV and ANDV differed in their individual requirements for regulatory factors of macropinocytosis, indicating virus-specific differences.
Insights
Hantaviruses enter human respiratory cells through macropinocytosis, a process requiring sodium proton exchangers and actin. However, Hantaan virus (HTNV) and Andes virus (ANDV) exhibit distinct cellular factor requirements for entry.
Area of Science:
- Virology
- Cell Biology
- Infectious Diseases
Background:
- Hantaviruses are rodent-borne RNA viruses causing severe human diseases.
- Zoonotic transmission occurs via aerosols, targeting human respiratory epithelial cells.
Purpose of the Study:
- Investigate cellular factors in Old and New World hantavirus entry into respiratory cells.
- Determine the endocytic pathway utilized by Hantaan virus (HTNV) and Andes virus (ANDV).
Main Methods:
- Screening of a kinase inhibitor library using a recombinant vesicular stomatitis virus pseudotype platform.
- Examination of inhibitors targeting endocytosis pathways, specifically macropinocytosis.
- Utilized human respiratory epithelial cells for entry studies.
Main Results:
- Identified differential host kinase requirements for HTNV and ANDV entry.
- Confirmed both HTNV and ANDV utilize macropinocytosis for cellular entry.
- Demonstrated virus-specific differences in the requirement for macropinocytosis regulatory factors.
Conclusions:
- Hantavirus entry into human respiratory epithelial cells critically depends on macropinocytosis.
- Distinct cellular mechanisms govern the entry of different hantaviruses, suggesting virus-specific adaptations.
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