Modification of foot-and-mouth disease virus O1 Caseros after serial passages in the presence of antiviral polyclonal sera

Abstract

Foot-and-mouth disease virus (FMDV) shows a remarkable antigenic variability and, like other RNA viruses, presents a high rate of mutation. It has been proposed that selection exerted by antibodies of the host could play a major role in the rapid evolution of FMDV. The present work reports the selection of FMDV antibody-resistant (Nr) populations after serial passages of a cloned FMDV 01 Caseros strain on secondary monolayers of bovine kidney cells in the presence of subneutralizing antiviral polyclonal sera (APS). After a limited number of passages, i.e., 29, under selective pressure, the virus population showed the following characteristics: (i) increased resistance to neutralization by APS (Nr), (ii) altered electrophoretic mobility of its structural viral proteins (VP1), and (iii) alterations at the RNA nucleotide sequence that codes for the major antigenic site of VP1. These acquired characteristics were detected at passage 15 and remained unmodified throughout successive passages. These results document a rapid selection and fixation of specific mutations in response to immunological pressure. In addition, the findings that (i) mutations not related to APS selection were not detected and (ii) after 29 passages at a high multiplicity of infection without immunological pressure, the RNA sequence that codes for VP1 remained unmodified clearly demonstrated that FMDV 01 Caseros presents in vitro a remarkable unexpected genetic stability.

Prediction and characterization of novel epitopes of serotype A foot-and-mouth disease viruses circulating in East Africa using site-directed mutagenesis

“…Four antigenic sites (equivalent to sites 1, 2, 4 and 5 of serotype O) were described for serotype A; site 1 (G-H loop of VP1) is linear and trypsin-sensitive, whereas the others are conformational and trypsin-resistant ( Thomas et al , 1988 ; Bolwell et al , 1989 ; Saiz et al , 1991 ; Mahapatra et al , 2011 ). Escape mutants are also studied using polyclonal antibodies in serotypes O and C ( Rojas et al , 1992 ; Schiappacassi et al , 1995 ; Kumar et al , 2004 ; Sarangi et al , 2013 ). In addition, the location of antibody binding sites (epitopes) can be inferred from correlating the antibody cross-reactivity of viruses to their capsid sequence similarities ( Reeve et al , 2010 ).…”

Many-trillionfold amplification of single RNA virus particles fails to overcome the Muller's ratchet effect

“…The great genetic diversity and variation present in a large population allow for selection of the fittest variants, and the population as a whole should generally increase in average fitness (8-10, 14, 15, 20, 24, 27, 28, 32, 34, 39, 53, 59, 62). This selection process may allow RNA viruses to escape immune system responses, resist virus inhibitors, and adapt rapidly to new host cell types and environments (14,28,31,39,47,50,61). Also, it may allow extremely debilitated viruses to gain very high fitness (7).…”

Hyper-antigenic variation occurs with human rhinovirus type 17

“…More recently, attempts have been made to isolate antigenic variants for FMDV (24). After 29 passages of FMDV O1 Caseros strain under selective pressure, the derived viral population had an increased ability to grow in the presence of specific antisera, suggesting that antisera-resistant populations had been selected (individual clones were not isolated).…”

“…It has been suggested that the high number of antigenic variants among rhinoviruses arises in nature because of immune selection (25,27). Borrego et al and Rojas et al (2,24) have isolated antigenic variants from FMDV in the presence and absence of immune selection. Capsid sequence analyses of these variants have shown that while amino acid substitutions result from passage in the absence of antibody, they are distinct from those found after immune selection.…”