Antibodies to the vitronectin receptor (integrin alpha V beta 3) inhibit binding and infection of foot-and-mouth disease virus to cultured cells

Abstract

The amino acid sequence Arg-Gly-Asp (RGD) is highly conserved on the VP1 proteins of different serotypes and subtypes of foot-and-mouth disease virus (FMDV) and is essential for cell attachment. This sequence is also found in certain extracellular matrix proteins that bind to a family of cell surface receptors called integrins. Within the Picornaviridae family, human enterovirus coxsackievirus A9 also has an RGD motif on its VP1 capsid protein and has recently been shown to utilize the vitronectin receptor integrin ␣ V ␤ 3 as a receptor on monkey kidney cells. Competition binding experiments between type A 12 FMDV and coxsackievirus A9 using BHK-21 and LLC-MK2 cells revealed shared receptor specificity between these two viruses. Polyclonal antiserum to the vitronectin receptor and a monoclonal antibody to the ␣ V subunit inhibited both FMDV binding and plaque formation, while a monoclonal antibody to the ␤ 3 subunit inhibited virus binding. In contrast, antibodies to the fibronectin receptor (␣ 5 ␤ 1) or to the integrin (␣ V ␤ 5) had no effect on either binding or plaque formation. These data demonstrate that the ␣ V ␤ 3 vitronectin receptor can function as a receptor for FMDV.

Evolution of Cell Recognition by Viruses: A Source of Biological Novelty with Medical Implications

“…HS-GAG (Chen et al, 1997b;Germi et al, 2002) Yellow fever virus HS-GAG (Germi et al, 2002) HCV LDLR protein family (Agnello et al, 1999;Monazahian et al, 1999); CD81 (Pileri et al, 1998;Flint et al, 1999); tamarin CD81 (Allander et al, 2000); human SR-BI (Scarselli et al, 2002) BVDV LDLR protein family (Agnello et al, 1999) GB virus C/hepatitis G virus LDLR protein family (Agnello et al, 1999) CSFV HS-GAG (Hulst et al, 2000(Hulst et al, , 2001 (continues) FMDV HS-GAG Sa-Carvalho et al, 1997;Fry et al, 1999;Baranowski et al, 2000); integrins v 3 (Fox et al, 1989;Berinstein et al, 1995;Jackson et al, 1997;Neff et al, 1998), v 6 (Jackson et al, 2000b), v 1 (Jackson et al, 2002), 5 1 (Jackson et al, 2000a) Picornaviridae (cardiovirus)…”

Amending Koch's postulates for viral disease: When “growth in pure culture” leads to a loss of virulence

“…Another example is provided by foot and mouth disease virus (FMDV). Naturally isolated viruses bind a v b 3 integrins for entry (coincidentally, the same receptor used by pathogenic hantaviruses) (Berinstein et al, 1995). In contrast, FMDV serially passaged in baby hamster kidney-21 (BHK-21) cells loses the restriction for integrin binding by acquiring mutations in the RGD sequence, while gaining the ability to use heparan sulfate as a receptor (Martínez et al, 1997).…”

Targeting the porcine immune system—Particulate vaccines in the 21st century

“…2). This virus also carries ligands for integrin receptors [71]: avb1 [72], avb3 [73,74]) avb6 [71], and avb8 [72]. However, it appears that the preferred integrins for virus binding are either not expressed or are poorly expressed on the DC [70].…”