Point mutations in the S protein connect the sialic acid binding activity with the enteropathogenicity of transmissible gastroenteritis coronavirus

Abstract

Enteropathogenic transmissible gastroenteritis virus (TGEV), a porcine coronavirus, is able to agglutinate erythrocytes because of sialic acid binding activity. Competitive inhibitors that may mask the sialic acid binding activity can be inactivated by sialidase treatment of virions. Here, we show that TGEV virions with efficient hemagglutinating activity were also obtained when cells were treated with sialidase prior to infection. This method was used to analyze TGEV mutants for hemagglutinating activity. Recently, mutants with strongly reduced enteropathogenicity that have point mutations or a deletion of four amino acids within residues 145 to 155 of the S protein have been described. Here, we show that in addition to their reduced pathogenicity, these mutants also have lost hemagglutinating activity. These results connect sialic acid binding activity with the enteropathogenicity of TGEV.

The enhanced replication of an S-intact PEDV during coinfection with an S1 NTD-del PEDV in piglets

“…BM is a mixture of highly glycosylated proteins containing sugar moieties, such as 5-N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2), 5-N-glycolylneuraminic acid (Neu5Gc), and 5-N-acetylneuraminic acid (Neu5Ac). Among them, Neu5Gc and Neu5Ac can serve as receptors or co-receptors for some alphacoronaviruses (e.g., TGEV) and gammacoronaviruses [e.g., infectious bronchitis virus (IBV)] (Cavanagh and Davis, 1986;Krempl et al, 1997). Similar to TGEV, which uses Neu5Gc and Neu5 Ac as co-receptors (Krempl et al, 1997;Schultze et al, 1996;Schwegmann-Wessels and Herrler, 2006), the S1 NTD of PEDV interacted with sugar (Deng et al, 2016).…”

Cholesterol is important for a post-adsorption step in the entry process of transmissible gastroenteritis virus

“…Haemagglutination-positive virions of TGEV were grown in desialylated cells treated with neuraminidase (NA) at 37 • C for 1 h as described previously (Krempl et al, 1997). Virus (2 × 10 5 pfu/ml) was treated with M␤CD (0, 4 and 10 mM) at 37 • C for 30 min.…”

“…To analyze the effect of cholesterol depletion on the sialic acid binding activity of TGEV, we applied a hemagglutination assay. Maximum HA titers are obtained with virions that have been enzymatically desialylated to remove sialic acids from the viral surface (Krempl et al, 1997(Krempl et al, , 2000. Therefore, purified virus was treated with neuraminidase prior to cholesterol depletion by M␤CD.…”

“…Other structural proteins are the integral membrane (M) glycoprotein, a minor envelope (E) protein, and the nucleocapsid (N) protein. Functionally, the S glycoprotein is the major target of neutralizing antibodies (Garwes et al, 1978;Jiménez et al, 1986;Laude et al, 1987;Antón et al, 1996;Sune et al, 1990), and it is also related to cell tropism (Jacobs et al, 1986;Torres et al, 1996;Sánchez et al, 1999;Schwegmann-Wessels et al, 2003), interaction with its cellular receptor (Collins et al, 1982;Delmas et al, 1990;Schwegmann-Wessels et al, 2002Liu et al, 2009;Shulla and Gallagher, 2009), pathogenicity (Krempl et al, 1997;Garwes et al, 1978;Tuboly et al, 1994), fusion (Collins et al, 1982;Spaan et al, 1988;Sune et al, 1990) and hemagglutination activity (Krempl and Herrler, 2001;Krempl et al, 2000).…”

Intragastric administration of Lactobacillus casei expressing transmissible gastroentritis coronavirus spike glycoprotein induced specific antibody production

“…The S protein has a membrane-anchoring domain and is highly glycosylated. It is also thought to be the viral attachment protein which interacts with the cell receptor, porcine aminopeptidase N (APN) [17,18]. As the major inducer of TGEV-neutralizing antibodies, the S protein has been used mainly for the induction of protective immunity to TGEV [19][20][21].…”