RESUMO
Genetic heterogeneity among closely related isolates of foot-and-mouth disease virus (FMDV) has been measured by direct sequencing of the VP1-coding-region RNA for three new FMDVs of serotype C1 and by additional sequences of RNA from previously reported isolates, all belonging to a single episode of disease [Sobrino et al., Gene 50 (1986) 149-159]. In the ten viruses compared, eight different VP1 are represented. The changes include amino acid substitutions at a critical antigenic determinant of VP1. We document that variations present in such natural isolates result in changes of the immunogenic properties of the viruses. Vaccines prepared with two of the FMDV C1 analyzed induce complete protection against an homologous virus but only partial protection against an heterologous virus in swine, the host from which these viruses were isolated.
Assuntos
Aphthovirus/genética , Capsídeo/genética , Animais , Anticorpos Antivirais/biossíntese , Antígenos Virais/genética , Aphthovirus/imunologia , Sequência de Bases , Capsídeo/imunologia , Epitopos/genética , Variação Genética , Dados de Sequência Molecular , RNA Viral/genética , Suínos/imunologia , Vacinas Virais/imunologiaRESUMO
A plaque-purified preparation of foot-and-mouth disease virus (FMDV) of serotype C1 (C-S8c1-1), grown in cell culture, was used to infect nonimmunized pigs. No variant genomes were detected in the average populations of 50 viruses isolated from infected animals by direct RNA sequencing of the carboxy-terminal half of the VP1 gene. However, a mutant with altered phenotypic properties was present in low proportion in an infected animal. The frequency of mutants resistant to neutralization by SD6 monoclonal antibody (MAb) [SD6 epitope MAb-resistant mutants (MARMs)], directly estimated in virus from lesions of infected animals (without passage in cell culture), depended on the procedure used for its determination and ranged from 2.9 x 10(-6) (when the virus was incubated with the MAb prior to plating) to 2.6 x 10(-5) (when incubation with MAb was avoided and the MAb was maintained in the agar overlay of the titration assay). Such a difference was not found for C-S8c1-1, which consistently showed frequencies of about 4 x 10(-5). In addition, the repertoire of amino acid substitutions was similar among SD6 epitope MARMs isolated directly both from vesicles of infected animals and from C-S8c1-1. Thus, in spite of the conservation of the average sequence in the region of VP1 RNA analyzed, antigenic heterogeneity has been found in viral populations of FMDV upon replication in nonimmunized swine.