Response of foot-and-mouth disease virus C3 Resende to immunological pressure exerted in vitro by antiviral polyclonal sera

The foot-and-mouth disease virus (FMDV) shows a remarkable antigenic variability. Like other RNA viruses, FMDV has a high mutation rate and its has been proposed that selection exerted by antibodies of the host could play a major role in its evolution. In this work, antiserum-resistant variants of FMDV (Nr variants) were selected upon 25 serial passages of a cloned C3 Resende strain on secondary monolayers of fetal bovine kidney (FBK-2) cells in the presence of subneutralizing levels of antiviral polyclonal sera (APS). After serial passage under immun selective pressure, the five Nr variant populations selected from five independent serial passages—their controls remaining, nmodified—acquired the following characteristics: (i) increased resistance to neutralization by APS; (ii) five different antigenic specifitities detected by enzyme-linked and neutralization assays using monoclonal antibodies; (iii) the same modification (residue 146, S to L) at the major antigenic site of VP1 (G-H loop, the 135–160 region); and (iv) specific changes for each Nr population outside the major antigenic site of VP1 at residues 46, 48 and 49 of the 40–60 region of VP1 (B-C loop). These results extend our previous work on selection of Nr variants using polyclonal sera, and add new information with regard to antigenic variation, mainly concerning the involvement of the 40–60 region of VP1 in the process of immune selection.