Structure, function and evolution of the hemagglutinin-esterase proteins of corona- and toroviruses

Abstract

Virus attachment to host cells is mediated by dedicated virion proteins, which specifically recognize one or, at most, a limited number of cell surface molecules. Receptor binding often involves protein-protein interactions, but carbohydrates may serve as receptor determinants as well. In fact, many different viruses use members of the sialic acid family either as their main receptor or as an initial attachment factor. Sialic acids (Sias) are 9-carbon negatively-charged monosaccharides commonly occurring as terminal residues of glycoconjugates. They come in a large variety and are differentially expressed in cells and tissues. By targeting specific Sia subtypes, viruses achieve host cell selectivity, but only to a certain extent. The Sia of choice might still be abundantly present on non-cell associated molecules, on non-target cells (including cells already infected) and even on virus particles themselves. This poses a hazard, as high-affinity virion binding to any of such "false'' receptors would result in loss of infectivity. Some enveloped RNA viruses deal with this problem by encoding virion-associated receptor-destroying enzymes (RDEs). These enzymes make the attachment to Sia reversible, thus providing the virus with an escape ticket. RDEs occur in two types: neuraminidases and sialate-O-acetylesterases. The latter, originally discovered in influenza C virus, are also found in certain nidoviruses, namely in group 2 coronaviruses and in toroviruses, as well as in infectious salmon anemia virus, an orthomyxovirus of teleosts. Here, the structure, function and evolution of viral sialate-O-acetylesterases is reviewed with main focus on the hemagglutinin-esterases of nidoviruses.

Effects of Sialic Acid Modifications on Virus Binding and Infection

“…Both toroviruses and group II coronaviruses often express an HE glycoprotein on the surface of their envelope in addition to the large binding and fusion active spike (S) protein [66]. Coronavirus and torovirus HEs appear to have originated through multiple horizontal gene transfer and recombination events between strains [67,68]. Interestingly, these HEs also appear homologous to the Orthymyxovirus family member influenza C HE glycoprotein, suggesting a common evolutionary ancestor for the protein resulting from gene exchange between these different viral taxa [69].…”

The Sialome—Far More Than the Sum of Its Parts

“…Natural modification of Sia core structures yield over 50 variations, which include esterification (with acetyl, lactyl, sulfate or phosphate), O-methylation, lactonization, or lactamization (Angata and Varki, 2002;Kelm and Schauer, 1997;Schauer, 1982Schauer, , 2009Troy, 1992;Varki, 1992;Varki and Schauer, 2009). These modifications can dramatically affect Sia recognition by glycan binding proteins (GBPs), for example, human and mouse sialoadhesin (Siglec-1) strongly prefers to bind Neu5Ac over Neu5Gc structures (Brinkman- Van der Linden et al, 2000), and certain viruses use terminal O-acetylated Sias for binding (Cornelissen et al, 1997;de Groot, 2006;Herrler et al, 1985;Regl et al, 1999;Rogers et al, 1986;Schwegmann-Wessels and Herrler, 2006;Suzuki, 2005;Vlasak et al, 1988).…”

Bitter-sweet symphony: glycan–lectin interactions in virus biology

“…A similar situation is seen for certain coronaviruses and toroviruses that carry an accessory protein called hemagglutinin‐esterase on their surface (de Groot, ). As the name implies, functional hemagglutinin‐esterase proteins combine a hemagglutinating activity with a sialate‐ O ‐acetylesterase activity (de Groot, ). Interestingly, for some coronaviruses, the hemagglutinin‐esterase protein is not the only envelope protein endowed with a lectin activity.…”