Feline infectious peritonitis

Amongst the many feline viruses, the agent that causes FIP is perhaps the most elusive and frustrating to diagnose and treat. Elizabeth Berliner offers a review of the disease and some pointers as to what may be around the corner in terms of therapy.

Elizabeth A. Berliner
DVM, Dipl. ABVP
 

Introduction

Feline Infectious Peritonitis (FIP) is the result of a mutation of the ubiquitous and relatively harmless feline coronavirus (FCoV). First described in 1963 ( 1 ), the rise and increased incidence of FIP since its discovery has been associated with husbandry practices that result in group-housed cats; this includes breeding and sheltering facilities. The first commercial cat litter appeared on the US market in 1947 ( 2 ) — a reflection of the changing role of the cat as an indoor companion animal — and both breeding and rescue operations increased in the following decades, creating opportunities for transmission and amplification of infectious diseases in groups of cats. To date, FIP has evaded medical prevention modalities as well as a cure; furthermore, ante-mortem diagnosis often remains a clinical challenge. Current research includes enhanced diagnostic tools utilizing molecular sequencing and clinical trials of new therapies; both of these areas suggest promising advances in the field.

Etiology and pathogenesis

Feline coronavirus is a large, enveloped, positive-stranded RNA virus. Coronaviruses in general exhibit a high rate of mutation during replication, which leads to intra-species and cross-species recombination and transmission. Currently, FCoV is considered to have two serotypes: type I, which is the most prevalent form found worldwide in naturally affected cats (with some geographic variation), and type II, which arose from a recombination event between type I FCoV and canine coronavirus. Although type 1 predominates in natural feline infections, the vast majority of research has been conducted on type II because it is more readily propagated in the laboratory for study. Both type I and type II FCoV serotypes have been implicated in FIP development ( 3 ). Type I and type II are distinguished by genetic differences in their S (spike) proteins (Figure 1), which are considered important in the transformation of common FCoVs to the FIP-causing FCoVs (FIPVs).

The main route of FCoV transmission is fecal-oral, with oronasal inoculation of the virus via direct transmission or fomites such as litterboxes or surfaces. After inoculation, FCoV moves into intestinal enterocytes, where the virus replicates. Infections with FCoV are often subclinical, but may result in a self-limiting diarrhea as the virus impacts the intestinal epithelium.

The transformation of the common FCoV to the lethal FIPV involves specific point mutations in the RNA genome. Structural features of interest are the viral spike (S) and membrane (M) proteins which act in allowing entry into and exit from cells (Figure 1). An understanding of specific point mutations is thought to be the key in unlocking this lethal transformation; current efforts are focused primarily on the S and 3c genes, with the S gene being most commonly implicated in laboratory studies to date ( 4 ).

The macrophage is the primary inflammatory cell in FIP. Point mutations in the FCoV genome switch the virus from an epithelial tropism to a macrophage trophism. The resulting virus is then able to travel and replicate in macrophages, moving into organs and other tissues. Infected macrophages internalize antigen, allowing the virus to evade antibody-dependent lysis, while also activating complement which increases the influx of other inflammatory cells to infected tissues. The humoral branch of the immune response is also activated, resulting in the deposition of antibody-antigen complexes along vessels, causing profound and widespread vasculitis. Approximately 50% of FIP cases develop effusive disease, while the other 50% develop the less-effusive granulomatous presentation; however, the classic dichotomy is a false one, as the disease acts along a spectrum between effusive and non-effusive signs. This variation is theorized to depend on which branch of the immune system is most active in responding: the humoral system results in more effusive disease, and the complement system in the more granulomatous presentation ( 5 ). [...]