Efficient infection of buffalo rat liver-resistant cells by encephalomyocarditis virus requires binding to cell surface sialic acids

Abstract

In contrast to the production of virus and cell lysis seen in baby hamster kidney cells infected with the strain 1086C of encephalomyocarditis virus (EMCV), in buffalo rat liver cells (BRL) neither virus replication nor cytopathic effects were observed. After 29 passages in BRL cells, each alternating with boosts of the recovered virus in BHK-21 cells, the virus acquired the ability to replicate effectively in BRL cells, attaining virus titres comparable to those in BHK-21 cells and producing complete cell destruction. The binding of virus on BRL cells was increased after adaptation and was similar to that observed on BHK-21 cells. Treatment of BRL cells with sialidase resulted in an 87 % reduction in virus binding and inhibition of infection. Sequence analyses revealed three mutations in the VP1 amino acid sequence of the adapted virus at positions 49 (LysAGlu), 142 (LeuAPhe) and 180 (IleAAla). The residue 49 is exposed at the surface of the capsid and is known to be part of a neutralization epitope. These results suggest that the adaptation of EMCV to BRL cells may have occurred through a mutation in a neutralizing site that confers to the virus a capacity to interact with cell surface sialic acid residues. Taken together, these data suggest a link between virus neutralization site, receptor binding and cell permissivity to infection.

The encephalomyocarditis virus

“…Thus, the main receptor for EMCV, as well as its viral binding partner, remains uncertain. A recent study suggests that the capacity of the virus to interact with cell surface sialic acid residues is important for infection of BRL cells 25 . However, it is interesting to note that sialic acid binding is not required for all EMCV strains 26 …”

Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis

“…In both cases, the observed effect on platelet count was TLR7 specific, as Loxo or EMCV injection in TLR7KO mice did not affect platelet numbers compared with saline-injected TLR7KO mice ( Figure 1F-G). Cell-surface sialic acid is a major entry receptor for this virus, 32 and platelets are extensively coated with it. 33 SEMs and TEMs revealed EMCV particles on the surface and inside of platelets with activated morphology (Figure 1H-I; supplemental Figure 1A-B).…”

Picornaviruses

“…Another cardiovirus, EMCV, binds via a sialic acid moiety to glycophorin A, which is a receptor molecule on virus nonpermissive mammalian erythrocytes (Tavakkol and Burness 1990). Recent studies have also shown that EMCV can use sialic acid-mediated entry after adaptation in cell culture (Guy et al 2009). The aphthovirus equine rhinitis A virus (ERAV) also attaches to cells via an interaction with sialic acid (Stevenson et al 2004; Warner et al 2001), and the structure of virus complexed with sialic acid has been obtained by X-ray crystallography (Fry et al unpublished).…”