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Article

Positively Charged Amino Acids in the Pestiviral Erns Control Cell Entry, Endoribonuclease Activity and Innate Immune Evasion

1
Institute of Virology and Immunology (IVI), CH-3001 Bern, Switzerland
2
Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, CH-3001 Bern, Switzerland
3
Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, CH-3012 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editors: Paul Becher, Nicolas Ruggli and Norbert Tautz
Viruses 2021, 13(8), 1581; https://doi.org/10.3390/v13081581
Received: 30 June 2021 / Revised: 4 August 2021 / Accepted: 5 August 2021 / Published: 10 August 2021
(This article belongs to the Special Issue Advances in Pestivirus Research)
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. View Full-Text
Keywords: pestivirus; bovine viral diarrhea virus (BVDV); viral endoribonuclease; IFN antagonist; immune evasion; glycosaminoglycan (GAG)-binding site; viral RNA; RNA-binding; site-directed mutagenesis; endocytosis pestivirus; bovine viral diarrhea virus (BVDV); viral endoribonuclease; IFN antagonist; immune evasion; glycosaminoglycan (GAG)-binding site; viral RNA; RNA-binding; site-directed mutagenesis; endocytosis
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MDPI and ACS Style

Lussi, C.; de Martin, E.; Schweizer, M. Positively Charged Amino Acids in the Pestiviral Erns Control Cell Entry, Endoribonuclease Activity and Innate Immune Evasion. Viruses 2021, 13, 1581. https://doi.org/10.3390/v13081581

AMA Style

Lussi C, de Martin E, Schweizer M. Positively Charged Amino Acids in the Pestiviral Erns Control Cell Entry, Endoribonuclease Activity and Innate Immune Evasion. Viruses. 2021; 13(8):1581. https://doi.org/10.3390/v13081581

Chicago/Turabian Style

Lussi, Carmela, Elena de Martin, and Matthias Schweizer. 2021. "Positively Charged Amino Acids in the Pestiviral Erns Control Cell Entry, Endoribonuclease Activity and Innate Immune Evasion" Viruses 13, no. 8: 1581. https://doi.org/10.3390/v13081581

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