Recovery and altered neutralization specificities of chimeric viruses containing capsid protein domain exchanges from antigenically distinct strains of feline calicivirus

Feline calicivirus (FCV) strains can show significant antigenic variation w hen tested for cross-reactivity,vith antisera produced against other FCV st rains. Previous work has demonstrated the presence of hypervariable amino a cid sequences in the capsid protein of FCV (designated regions C and E) tha t were postulated to constitute the major antigenic determinants of the vir us. To examine the involvement of hypervariable sequences in determining th e antigenic phenotype, the nucleotide sequences encoding the E regions from three antigenically distinct parental FCV strains (CFI, KCD, and NADC) wer e exchanged for the equivalent sequences in an FCV Urbana strain infectious cDNA clone. Two of the three constructs were recovered as viable, chimeric viruses. In six additional constructs, of which three were recovered as vi able virus, the E region from the parental viruses was divided into left (N -terminal) and right (C-terminal) halves and engineered into the infectious clone. A final viable construct contained the C, D, and E regions of the N ADC parental strain. Recovered chimeric viruses showed considerable antigen ic variation from the parental viruses when tested against parental hyperim mune serum, No domain exchange was able to confer complete recognition by p arental antiserum with the exception of the KCD E region exchange, which wa s neutralized at a near-homologous titer with KCD antiserum. These data dem onstrate that it is possible to recover engineered chimeric FCV strains tha t possess altered antigenic characteristics. Furthermore, the E hypervariab le region of the capsid protein appears to play a major role in the formati on of the antigenic structure of the virion where conformational epitopes m ay be more important than linear in viral neutralization.