The Erns Carboxyterminus: Much More Than a Membrane Anchor.

Birke Andrea Tews,Till Rümenapf,Juliane Kühn,Kati Franzke,Gregor Meyers,Anne Klingebeil

doi:10.3390/v13071203

Birke Andrea Tews, Till Rümenapf + Show 4 more

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https://doi.org/10.3390/v13071203

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Abstract

Pestiviruses express the unique essential envelope protein Erns, which exhibits RNase activity, is attached to membranes by a long amphipathic helix, and is partially secreted from infected cells. The RNase activity of Erns is directly connected with pestivirus virulence. Formation of homodimers and secretion of the protein are hypothesized to be important for its role as a virulence factor, which impairs the host’s innate immune response to pestivirus infection. The unusual membrane anchor of Erns raises questions with regard to proteolytic processing of the viral polyprotein at the Erns carboxy-terminus. Moreover, the membrane anchor is crucial for establishing the critical equilibrium between retention and secretion and ensures intracellular accumulation of the protein at the site of virus budding so that it is available to serve both as structural component of the virion and factor controlling host immune reactions. In the present manuscript, we summarize published as well as new data on the molecular features of Erns including aspects of its interplay with the other two envelope proteins with a special focus on the biochemistry of the Erns membrane anchor.

Highlights

IntroductionComparison of the features and known functions of these proteins with those from the related hepaciviruses reveals that pestiviral E1 and E2 are basically equivalent to the hepaciviral proteins with the same names whereas Erns obviously represents a unique product
Published: 23 June 2021Pestiviruses are unique in the family Flaviviridae because they express three structural glycoproteins, Erns, E1 and E2, that all are essential for generation of infectious viruses [1,2].Comparison of the features and known functions of these proteins with those from the related hepaciviruses reveals that pestiviral E1 and E2 are basically equivalent to the hepaciviral proteins with the same names whereas Erns obviously represents a unique product
The Erns protein of pestiviruses represents a very special product of viral evolution, a kind of a swiss army knife that integrates a role as structural protein essential for generation of infectious viral particles and a virulence factor function important for controlling the host’s innate immune response to pestivirus infection

Summary

Introduction

Comparison of the features and known functions of these proteins with those from the related hepaciviruses reveals that pestiviral E1 and E2 are basically equivalent to the hepaciviral proteins with the same names whereas Erns obviously represents a unique product This conclusion is supported by data showing that in pseudotyped viruses pestiviral E1 and E2 are sufficient for infection of cells [3,4] whereas Erns has to play some unknown additional role as a structural protein in the pestivirus life cycle. Erns represents a virulence factor of pestiviruses [5,6,7,8] This function depends on a highly unusual enzymatic activity, which has so far not been found in any other viral surface protein.

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