RESPONSE OF FOOT-AND-MOUTH-DISEASE VIRUS C-3 RESENDE TO IMMUNOLOGICALPRESSURE EXERTED IN-VITRO BY ANTIVIRAL POLYCLONAL SERA

The foot-and-mouth disease virus (FMDV) shows a remarkable antigenic v ariability. Like other RNA viruses, FMDV has a high mutation rate and it has been proposed that selection exerted by antibodies of the host could play a major role in its evolution. In this work, antiserum-resi stant variants of FMDV (Nr variants) were selected upon 25 serial pass ages of a cloned C-3 Resende strain on secondary monolayers of fetal b ovine kidney (FBK-2) cells in the presence of subneutralizing levels o f antiviral polyclonal sera (APS). After serial passage under immune s elective pressure, the five Nr variant populations selected from five independent serial passages-their controls remaining unmodified-acquir ed the following characteristics: (i) increased resistance to neutrali zation by APS; (ii) five different antigenic specificities detected by enzyme-linked and neutralization assays using monoclonal antibodies; (iii) the same modification (residue 146, S to L) at the major antigen ic site of VP1 (G-H loop, the 135-160 region); and (iv) specific chang es for each Nr population outside the major antigenic site of VP1 at r esidues 46, 48 and 49 of the 40-60 region of VPI (B-C loop). These res ults extend our previous work on selection of Nr variants using polycl onal sera, and add new information with regard to antigenic variation, mainly concerning the involvement of the 40-60 region of VP1 in the p rocess of immune selection.