Rapid selection of genetic and antigenic variants of foot-and-mouth disease virus during persistence in cattle

Abstract

Rapid evolution of foot-and-mouth disease virus (FMDV) is documented during persistent infections of cattle. The carrier state was established experimentally with plaque-purified FMDV of serotype C3. Virus was recovered from the esophageal pharyngeal area of the animals up to 539 days postinfection. Analysis of capsid proteins by electrofocusing and by electrophoretic mobility of the genomic poly(C)-rich tract suggested heterogeneity in several isolates and sequential dominance of viral subpopulations. Nucleotide sequences of the VPI-coding region of the parental FMDV C3 clones and of seven isolates from the carrier cattle showed point mutations that represented rates of fixation of mutations of 0.9 x 10-2 to 7.4 x 10-2 substitutions per nucleotide per year; 59% of the base changes led to amino acid substitutions, some of which were located within residues 135 to 151, a region involved in neutralization of FMDV. In the esophageal pharyngeal fluid samples, FMDV C3-neutralizing activity was present. Antigenic variation was demonstrated with monoclonal antibodies raised against FMDV C3. Two isolates from carrier cattle differed from the parental virus by 102_ or 103-fold decreased reactivity with neutralizing monoclonal antibodies. We suggest that persistent, inapparent infections of ruminants, in addition to being a reservoir of virus, may promote the rapid selection of antigenically variant FMDVs.

Seasonality and selective trends in viral acute respiratory tract infections

“…Three more recent reports described the recovery of spontaneously-generated ts strains of influenza A from persistent infections of cell cultures [70][71][72]. Similar tendencies are seen in persistent infections of animals; footand-mouth viruses recovered from carrier animals are frequently ts, and show evidence of high rates of mutation with frequent amino acid substitutions and rapid antigenic variation [73].…”

Interaction of virus populations with their hosts

“…Mutations that mediate escape from neutralizing antibodies and from CTLs can be readily observed in vivo (Weiner et al, 1995;Borrow et al, 1997;McMichael and Phillips, 1997;Ciurea et al, 2000;Sevilla et al, 2002). Rather than being a secondary phenomenon in the course of viral infections, the generation of antibody-and CTL escape mutants may indeed contribute to viral persistence (Gebauer et al, 1988;Ciurea et al, 2000;Richman et al, 2003;Domingo, 2006). Evasion of an immune response, as the outcome of a selection event in viruses, may entail a fitness cost.…”

Interaction of Virus Populations with Their Hosts

“…Mutations that mediate escape from neutralizing antibodies and from CTLs can be readily observed in vivo (Weiner et al, 1995;Borrow et al, 1997;McMichael and Phillips, 1997;Ciurea et al, 2000;Sevilla et al, 2002). Rather than being a secondary phenomenon in the course of viral infections, the generation of antibody-and CTL escape may indeed contribute to viral persistence (Gebauer et al, 1988;Ciurea et al, 2000;Richman et al, 2003;Domingo, 2006). Evasion of an immune response, as the outcome of a selection event in viruses, may entail a fitness cost.…”