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Modulation of ADAM17 Levels by Pestiviruses Is Species-Specific.

Hann-Wei Chen¹, Marianne Zaruba¹, Aroosa Dawood¹

¹Institute of Virology, Department of Pathobiology, University of Veterinary Medicine, 1210 Vienna, Austria.

|October 26, 2024

Summary

Pestivirus infections reduce levels of the cell surface sheddase ADAM17 in a species-specific manner. This reduction may play a role in preventing further viral entry, a phenomenon known as superinfection exclusion.

Keywords:

ADAM17 maturation pestivirus receptor downregulation

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Area of Science:

Virology
Cell Biology
Immunology

Background:

Viruses manipulate host cells for replication, often downregulating viral entry receptors.
ADAM17, a metalloproteinase, is crucial for pestivirus entry into bovine cells.

Purpose of the Study:

To investigate the impact of pestivirus infection on ADAM17 expression and cell surface localization.
To explore the potential role of ADAM17 downregulation in pestivirus superinfection exclusion.

Main Methods:

Quantification of cellular and cell surface ADAM17 levels in pestivirus-infected cells.
Assessment of superinfection exclusion in cells persistently infected with different pestiviruses.

Main Results:

Cytopathic bovine viral diarrhea virus (cpBVDV), classical swine fever virus (CSFV), and giraffe pestivirus reduced mature ADAM17 levels.
ADAM17 surface levels decreased with BVDV and CSFV E2 proteins, but not with Linda virus or atypical porcine pestivirus E2.
Linda virus-infected cells showed higher susceptibility to cpBVDV challenge compared to CSFV-infected cells.

Conclusions:

Pestivirus infection exhibits species-specific effects on ADAM17 levels.
ADAM17 downregulation may contribute to superinfection exclusion in certain pestivirus infections.