Deciphering foot-and-mouth disease (FMD) virus–host tropism

The pattern of interactions between foot and mouth disease (FMD) viral protein 1 (VP1) with susceptible and resistant host integrins were deciphered. The putative effect of site-directed mutation on alteration of interaction is illustrated using predicted and validated 3D structures of VP1, mutated VP1 and integrins of <i>Bos taurus</i>, <i>Gallus</i> and <i>Canis</i>. Strong interactions were observed between FMDV-VP1 protein motifs at conserved tripeptide, Arg-Gly-Asp ¹⁴³RGD¹⁴⁵ and at domain ⁶⁷⁶SIPLQ⁶⁸⁰ in alpha-integrin of <i>B. taurus.</i> Notably, <i>in-silico</i> site-directed mutation in FMDV-VP1 protein led to complete loss of interaction between FMD-VP1 protein and <i>B. taurus</i> integrin, which confirmed the active role of arginine-glycine-aspartic acid (RGD) domain. Interestingly, <i>in-vitro</i> analysis demonstrates the persistence of the putative tropism site ‘SIPLQ’ in different cattle breeds undertaken. Thus, the attempt to decipher the tropism of FMDV at host receptor level interaction might be useful for future FMD control strategies through development of mimetic marker vaccines and/or host receptor manipulations. Communicated by Ramaswamy H. Sarma