Illustration by Paul Petersen
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Feline infectious peritonitis (FIP) remains a daunting disease—its pathogenesis is unclear, it can be difficult to diagnose,
especially in the dry form, and it is uniformly fatal. While research into this disease and its causative agent has not answered
all the questions, more is being learned, diagnostic tests are improving, and treatment may be on the horizon. This review
offers an update on our current knowledge about FIP.
THE CAUSATIVE AGENT
FIP is caused, at least in part, by feline coronavirus. This virus is related to the enteric canine coronavirus as well as
the agent of transmissible gastroenteritis in swine. It is an enveloped virus, which is unusual for enteric pathogens, and
contains a large RNA genome. This large genome is correlated with a high virus mutation rate through nucleotide substitutions,
deletions, and recombination events. The virus's mutability may play a role in the development of virulence.
Feline coronavirus is divided into two serotypes based on virus antigenicity. Most field strains are type 1; type 2 is a recombinant
of feline and canine coronaviruses.1 FIP may be caused by either serotype, although most cases are associated with type 1.2 However, most feline coronavirus infections produce no or only mild disease that typically manifests as diarrhea.
Feline coronavirus infections are common, especially in multicat situations. The virus is widespread, occurring worldwide
and in domestic and nondomestic felids. Serologic studies indicate high prevalence rates in most feline populations. The virus
is spread primarily by fecal-oral transmission, and infected cats may remain chronically infected, shedding the virus continuously
or intermittently for long periods.3 Indirect transmission of the virus may occur; the virus is easily inactivated with detergents used on nonporous surfaces
but may persist in the environment for several weeks. Kittens born into populations in which feline coronavirus is endemic
may become infected by 4 to 6 weeks of age.4
FIP is an uncommon manifestation of feline coronavirus infection, occurring in only 5% to 10% of infected cats.5 Why most cats suffer no serious consequences of feline coronavirus infection, while some develop a lethal disease, remains
uncertain. Virus factors are important in FIP development, as some strains are highly virulent and cause FIP in experimentally
infected cats. In addition, FIP outbreaks have occasionally occurred.6,7 It has been speculated that a mutation in the infecting virus leads to a change in the virus's biotype, from one causing
mild enteritis to one causing FIP.8,9 However, no genetic mutation that consistently correlates with FIP production has been identified. So why do only certain
cats progress to FIP?
PATHOGENESIS
The pathogenesis of FIP is complex and still not completely understood. The feline coronavirus is required but may not alone
cause the disease. This virus is spread via fecal-oral transmission and survives transit through the gastrointestinal tract.
It enters the intestinal epithelia from the lumen, with replication leading to the death of the epithelial cells that may
manifest as diarrhea.3 From the intestines, the virus may spread to infect monocytes and macrophages. This acquisition of monocyte/macrophage tropism
by the virus is a critical factor for FIP development—in cats that develop FIP, it appears that the virus replicates efficiently
in these cells, achieving high viral levels in the blood.10
One study found that the feline coronavirus spike protein provides target cell specificity and is the critical determinant
for macrophage infection.11 The region of the spike protein that mediates viral envelope fusion with the cell membrane during virus entry is the critical
domain that determines macrophage tropism. Regardless of how the monocyte/macrophage tropism arises, the efficient replication
of feline coronavirus in these cells is a key factor in FIP development. High levels of viral RNA have been detected in blood
and tissue of cats with FIP.10,12 However, this property alone does not appear to be sufficient to lead to FIP development, as another study found that high
viral load was not associated with clinical signs or pathology.13 Thus, systemic spread and replication are not unique to FIP.
Other viral genes speculated to play a role in FIP development are those encoding the coronavirus nonstructural proteins,
in particular the 3c and 7b genes.8,9 The function of these gene products is unknown, but they are theorized to be important in the virus's virulence. The evolution
of the FIP-causing ability may in fact involve multiple mutations. On the other hand, at least one study found no evidence
of mutation in the virus identified in FIP lesions.14 Thus, consensus on the precise nature of the viral contribution to FIP development has not been reached.
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