For each category of FIPV or FECV infection, cats harboring viruses with or without mutations at the S1/S2 site were counted.
To perform comparative analysis of the S1/S2 cleavage site between FECVs and FIPVs, we identified cases of FIP that were confirmed postmortem by using immunohistochemistry, the standard for FIP diagnosis; archival immunohistochemistry-positive formalin-fixed tissues were used as the source of FIPV RNA.
Analysis of the S1/S2 cleavage site of FIPV sequences shows that it has much more variability, both within the narrow furin cleavage recognition motif (P4-P1) and in residues extending out of it (P8-P5 and P2'-P4') (Figure 2A).
In contrast, FIPV is rare, but the consequences of infection are devastating.
To establish a consistent cause for a virulence shift in FCoV, specifically the predominant serotype I FCoV, we sequenced the entire genome of several FECV and FIPV specimens and then concentrated on the most conspicuous region of consistent difference by collecting and sequencing additional FECV and FIPV samples.
FIPV UU3 was obtained from a lymph node of a cat infected with FECV UCD; the presence of feline infectious peritonitis in the cat was pathologically confirmed.
FECV and FIPV cases were found in 7 (designated A to G); the remaining cattery (H) provided 2 cats with FIP.
When compared by phylogenetic analysis, the nucleotide sequences of FIPV and FECV M genes distributed into paraphyletic patterns rather than in monophyletic clusters (Figure, panel A).
Viral genetic determinants specifically associated with FIPV pathogenesis have yet to be discovered.
The in vivo mutation hypothesis of FIPV pathogenesis is widely cited, although it has never been explicitly confirmed.
Together with porcine Transmissible gastroenteritis virus (TGEV), canine coronavirus, and human coronavirus 229E (HCV), the feline coronaviruses form a separate cluster within, the genus Coronavirus, including Feline enteric coronavirus, and FIPV (26).
Antibody-dependent enhancement of FIPV has been demonstrated in vitro in feline macrophages as well as in stable human and mouse macrophage cell lines (29).