Identification of antigenic sites mediating antibody-dependent enhancement of feline infectious peritonitis virus infectivity

Abstract

We have previously demonstrated antibody-dependent enhancement of feline infectious peritonitis virus (FIPV) infection of macrophages using both virus-specific antisera and monoclonal antibodies (MAbs) to the spike (S) protein of FIPV. To increase our understanding of this phenomenon, six representative MAbs from a previously documented group of 12 enhancing MAbs were used to identify epitopes that mediate antibodydependent enhancement of FIPV infectivity. Analysis of the results of kinetics-based competitive ELISA (KcELISA) among these six enhancing MAbs grouped the epitopes into two clusters. Because transmissible gastroenteritis virus (TGEV) and FIPV are so closely related antigenically, we also conducted K-cELISA experiments between the FIPV MAbs and TGEV S protein-specific MAbs for which the epitopes had previously been mapped to specific sites on the TGEV S protein. Results of these assays indicated that the two FIPV epitope clusters are homologues of the previously defined TGEV S protein sites A and E/F. In addition, two TGEV S protein-specific MAbs also induced antibody-dependent enhancement of FIPV infection of macrophages. This functional cross-reactivity provides further support for the close antigenic relationship between FIPV and TGEV. Our results provide a preliminary localization of several enhancing epitopes within the amino acid sequence of the FIPV S protein.

Antibody-Dependent Enhancement Occurs Upon Re-Infection with the Identical Serotype Virus in Feline Infectious Peritonitis Virus Infection

“…Analysis using anti-FIPV MAb revealed that epitopes involved in ADE exist mainly on the S protein. Antibodies which neutralized virus propagated in Fc receptor-negative cells, such as the feline kidney cell line CrFK, induced strong ADE activity in Fc receptor-positive feline macrophages infected with FIPV, suggesting a close association between the neutralizing and infection-enhancing epitopes [2,11,17,18]. There are two serotypes of FIPV, types I and II [9,14,15].…”

SARS Vaccine Development

“…Whether these antibodies enhance infection by heterologous SARS-CoV strains or mediate harmful immune responses is unclear. The S protein of FIPV expressed by recombinant vaccinia can cause antibody-dependent enhancement of disease if vaccinated animals are subsequently infected with wild-type virus (32). Our previous studies on HIV-1 showed that antibodies against some immunodominant epitopes in the HIV-1 envelope glycoprotein could enhance infection by heterologous HIV-1 strains (33).…”

Antibody-Dependent Enhancement of Feline Infectious Peritonitis Virus Infection in Feline Alveolar Macrophages and Human Monocyte Cell Line U937 by Serum of Cats Experimentally or Naturally Infected with Feline Coronavirus.

“…We have recently reported that type I FIPVs including the UCD-1 strain have spike genes that are distinctly different from those of type II FIPVs, TGEV and CCV [18,19]. It has been reported that neutralization/enhancement site of the type II FIPV 79-1146 strain is located at the site corresponding to neutralization site A identified on TGEV S protein [3,20]. When nucleotide sequences at this site in TGEV strain Purdue, FIPV strains 79-1146 and KU-2 were compared, the sequence homology showed 93.9% identity between the Purdue strain and the 79-1146 strain, 49.3% between the Purdue strain and the KU-2 strain and 50.4% between the 79-1146 strain and the KU-2 strain (data not shown).…”