Mutation of neutralizing/antibody-dependent enhancing epitope on spike protein and 7b gene of feline infectious peritonitis virus: Influences of viral replication in monocytes/macrophages and virulence in cats

Abstract

We previously prepared neutralizing monoclonal antibody (MAb)-resistant (mar) mutant viruses using a laboratory strain feline infectious peritonitis virus (FIPV) 79-1146 (Kida et al., 1999). Mar mutant viruses are mutated several amino acids of the neutralizing epitope of Spike protein, compared with the parent strain, FIPV 79-1146. We clarified that MAb used to prepare mar mutant viruses also lost its activity to enhance homologous mar mutant viruses, strongly suggesting that neutralizing and antibody-dependent enhancing epitopes are present in the same region in the strain FIPV 79-1146. We also discovered that amino acid mutation in the neutralizing epitope reduced viral replication in monocytes/macrophages. We also demonstrated that the mutation or deletion of two nucleotides in 7b gene abrogate the virulence of strain FIPV 79-1146.

Identification and genotyping of feline infectious peritonitis-associated single nucleotide polymorphisms in the feline interferon-γ gene

“…The occurrence of FIP is thought to be largely affected by viral virulence factors, and their roles in FIP have been intensely studied. Several viral genes, including spike [31][32][33], accessory gene 3c [34][35][36] and 7b [37][38][39], and membrane [40], have been proposed to play important roles in the development of the disease in FCoV-infected cats. As a disease with immunopathogenesis entity, the knowledge of the host genetic factors that affect FIP is still very limited, and only two studies have reported such factors [41,42], in contrast to the considerable quantity of information on the virulence factors.…”

An update on feline infectious peritonitis: Virology and immunopathogenesis

“…Out of 30 peptides derived from this region that were tested in mice, four peptides that included both Th1 and Th2 epitopes were identified; the authors concluded that these regions should be explored in cats as potential immunogens. Takano et al (2011b) also studied the putative ADE epitopes in FIPV WSU-79-1146 with a battery of monoclonal antibodies against the virus neutralizing epitope on the S protein. Virus cultures exposed to one of these monoclonal antibodies eventually yielded a virus with two amino acid changes in the neutralizing epitope of the S protein that rendered it resistant to neutralization.…”

Feline Coronavirus in Multicat Environments

“…93 RT-PCR cannot discriminate between FECV and FIPV due to the various single nucleotide polymorphisms (SNPs) and deletion mutations present in both biotypes, sometimes even identified from the same cat. 46,164,165 At the time of writing, no specific genetic determinants that trigger the evolution of FECV to FIPV or otherwise distinguish the 2 biotypes have been confirmed. Due to these particularities of FCoV, a specific RT-PCR for FIPV cannot, as yet, be designed.…”