Lussi, Carmela; De Martin, Elena; Schweizer, Matthias (2021). Positively Charged Amino Acids in the Pestiviral Erns Control Cell Entry, Endoribonuclease Activity and Innate Immune Evasion. Viruses, 13(8) Molecular Diversity Preservation International MDPI 10.3390/v13081581
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The genus Pestivirus, family Flaviviridae, includes four economically important viruses of livestock, i.e., bovine viral diarrhea virus-1 (BVDV-1) and -2 (BVDV-2), border disease virus (BDV) and classical swine fever virus (CSFV). Erns and Npro, both expressed uniquely by pestiviruses, counteract the host's innate immune defense by interfering with the induction of interferon (IFN) synthesis. The structural envelope protein Erns also exists in a soluble form and, by its endoribonuclease activity, degrades immunostimulatory RNA prior to their activation of pattern recognition receptors. Here, we show that at least three out of four positively-charged residues in the C-terminal glycosaminoglycan (GAG)-binding site of BVDV-Erns are required for efficient cell entry, and that a positively charged region more upstream is not involved in cell entry but rather in RNA-binding. Moreover, the C-terminal domain on its own determines intracellular targeting, as GFP fused to the C-terminal amino acids of Erns was found at the same compartments as wt Erns. In summary, RNase activity and uptake into cells are both required for Erns to act as an IFN antagonist, and the C-terminal amphipathic helix containing the GAG-binding site determines the efficiency of cell entry and its intracellular localization.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology 05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Lussi, Carmela, De Martin, Elena, Schweizer, Matthias |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 590 Animals (Zoology) 600 Technology > 610 Medicine & health 600 Technology > 630 Agriculture |
ISSN: |
1999-4915 |
Publisher: |
Molecular Diversity Preservation International MDPI |
Language: |
English |
Submitter: |
Pamela Schumacher |
Date Deposited: |
18 Nov 2021 08:31 |
Last Modified: |
05 Dec 2022 15:54 |
Publisher DOI: |
10.3390/v13081581 |
PubMed ID: |
34452446 |
Uncontrolled Keywords: |
IFN antagonist RNA-binding bovine viral diarrhea virus (BVDV) endocytosis glycosaminoglycan (GAG)-binding site immune evasion pestivirus site-directed mutagenesis viral RNA viral endoribonuclease |
BORIS DOI: |
10.48350/160707 |
URI: |
https://boris.unibe.ch/id/eprint/160707 |