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

Abstract

ABSTRACT. Feline infectious peritonitis virus (FIPV) is classified into serotype I and serotype II according to the amino acid sequence of its spike(S) protein. Antibody dependent enhancement (ADE) of macrophage infection occurs in the presence of antibodies to FIPV S protein, and a close relationship between ADE and neutralizing epitopes has been reported. The importance of differences in FIPV serotype on the induction of ADE remains unclear. In this study, we investigated whether the same or different serotype of FIPV induces ADE in cats. Specific pathogen-free cats were passively immunized with anti-type I or II FIPV antibodies, and we investigated the induction of ADE following subcutaneous inoculation with type I FIPV. Inoculation using FIPV serotype I enhanced the onset of FIP in cats passively immunized with FIPV serotype I-specific antibodies but not in those passively immunized with antibodies to FIPV serotype II. These data suggest that re-infection with the same serotype induces ADE in cats infected with FIPV. KEY WORDS: ADE, coronavirus, FIPV, serotype.J. Vet. Med. Sci. 70(12): 1315-1321, 2008 Feline infectious peritonitis virus (FIPV), a feline coronavirus (FCoV) in the family Coronaviridae, causes fatal disease in wild and domestic cat species. FCoV is an enveloped virus with a single-stranded positive-sense RNA genome. The FCoV virions consist of three main structural proteins, peplomer spike (S) protein, transmembrane (M) protein and nucleocapsid (N) protein [16]. FCoV is classified into types I and II according to the amino acid sequence of its S protein and the reactivity to anti-FIPV S monoclonal antibodies (MAb) [9,14,15]. FCoV is also classified into 2 biotypes based on differences in pathogenicity: feline enteric coronavirus (FECV) and FIPV. Cats infected with FECV do not develop disease, but FIPV infection induces feline infectious peritonitis (FIP). FIP is a fatal disease, mainly leading to the development of immune complex vasculitis accompanied by necrosis and pyogenic granulomatous inflammation. It has been proposed that FIPV arises from FECV by mutation but the exact mutation and the inducing factors have not yet been clarified [21,27].Type II FCoV is known to utilize feline aminopeptidase N (fAPN) as its virus receptor [7]. FIPV targets macrophages, and macrophage infection is enhanced in the presence of antibodies (antibody-dependent enhancement, ADE). ADE activity in FIPV infection is induced when anti-FIPV-S antibody-bound viruses infect macrophages by binding of the Fc region of the antibody to the Fc receptor on the macrophage surface [2,10,18]. In addition to FIPV, there have been several reports concerning ADE of other virus infections (dengue virus, human immunodeficiency virus and respiratory syncytial virus, etc.) [4,5,20,22,23,25].We previously reported that when feline macrophages or human cells of monocyte lineage were inoculated with type II FIPV that had been reacted with the serum of type I or II FIPV-infected cats, ADE was observed only when type II FIPV was reacted ...

Lethal Antibody Enhancement of Dengue Disease in Mice Is Prevented by Fc Modification

“…These models show several parallels with our model of antibody-enhanced DENV infection: with FIPV, immune sera are able to enhance macrophage infection and disease during subsequent challenge with the same FIPV serotype in kittens [41],[46], and with MVEV, JEV, and YFV, enhanced mortality was observed in mice administered flavivirus cross-reactive polyclonal antibodies or non-neutralizing YFV-specific monoclonal antibodies [42]–[45]. However, none of these pathogens are associated with antibody-enhanced disease in humans.…”

“…In vivo ADE models have also been established for other viruses, including Yellow Fever Virus (YFV), Murray Valley Encephalitis Virus (MVEV), Japanese Encephalitis Virus (JEV), and Feline Infectious Peritonitis Virus (FIPV) [41]–[46], in which passive transfer of antibody increases viral titers and/or mortality. These models show several parallels with our model of antibody-enhanced DENV infection: with FIPV, immune sera are able to enhance macrophage infection and disease during subsequent challenge with the same FIPV serotype in kittens [41],[46], and with MVEV, JEV, and YFV, enhanced mortality was observed in mice administered flavivirus cross-reactive polyclonal antibodies or non-neutralizing YFV-specific monoclonal antibodies [42]–[45].…”

Recombinant feline coronaviruses as vaccine candidates confer protection in SPF but not in conventional cats

“…FIPV could negatively influence immune system intervening at several points. This virus variant is a highly virulent monocyte/macrophage pathogen causing systemic immune complex mediated infection (Vennema et al, 1998;Takano et al, 2008;Chang et al, 2010). These facts may explain why the acquired natural immunity in cats is rather limited against FIPV and also why no efficacious vaccine is available against FIPV despite the intensive efforts of academic and commercial researchers.…”

Replication of coronavirus

“…Tavuk ve domuzlar için kullanılan bu aşılar zayıflatılmış PEDV ve IBV virüsleridir (114,126). Kedi coronavirüslerine (FCoV) karşı geliştirilen aşılar kedilerde çok ciddi yan etkiler göstermektedir ve hastalığı daha da ağırlaştırmaktadır (127,128).…”