The FCoV carrier state

Epidemiological studies suggest that FCoVs may cause persistent infections, that a carrier state exists, and that many infections are not cleared by the cat's immune system - or only after a long time. It is common knowledge that healthy cats with coronavirus antibodies may cause seroconversion in contact animals within 2 to 10 weeks. The infection is spread presumably via the fecal-oral route, and some of the contact animals will subsequently succumb to FIP [1]. First solid evidence for a carrier state came from an experiment in which cats were infected with a sublethal dose of tissue culture grown FIPV and kept in isolation. To induce FIP, the cats were superinfected with feline leukaemia virus, which is known to be strongly T-cell immunosuppressive. From this work it appeared that FIPV could persist in the experimentally infected host for at least 4 months [11].

To identify asymptomatic FCoV carriers and to monitor virus shedding, a group of scientists from Utrecht developed a nested RT-PCR assay targeted to a highly conserved (invariant) region of the FCoV genome. Using this assay, viral RNA had previously been detected in the faeces, tissues and body fluids of cats with FIP [2,9]. Interestingly, however, FCoV RNA was also found in the faeces, and occasionally in the serum, of perfectly healthy cats. The virus persistence and evolution was then studied in a closed cat breeding facility in Hanover/Germany with an endemic FCoV type I infection. Viral RNA was detected in the faeces and/or plasma of 85% of the cats tested. Of five cats identified as FCoV shedders during the initial survey, four had viral RNA in their faeces when tested almost four months later. This could be due either to repeated reinfections or to persistence of the virus in the cat's organism. To distinguish between these possibilities, two cats were placed in perfect isolation, and fecal virus shedding was monitored every 2-4 days. In one cat, shedding continued for up to seven months. The other animal was sacrificed after three months of continuous shedding since we wanted to find the sites of viral replication. Viral genomic RNA was found in almost any tissue tested, but messenger RNA (which is synthesized only when a virus multiplies) was detected exclusively in the ileum, colon and rectum; in these parts of the gut individual FCoV-infected cells (i.e. not large parts of infected tissue) were also spotted by immunohistochemistry. These findings provide first formal evidence that FCoV causes chronic infections [10].

Recently, a modification of the conventional RT-PCR procedure was introduced - the so-called TaqMan technique. It allows testing of many samples within a short period of time, and in addition permits the reliable quantitation of FCoV genomes in a sample, e.g. in rectal swabs taken from individual cats [7] (for details of the TaqMan technique, look into the Tools section of this VetSciTe issue). Using this technique, the coronavirus shedding pattern was determined over a period of 24 weeks in 77 cats kept in multi-cat household situations. We found a highly significant correlation between the amount of FCoV shed in feaces and the frequency of shedding [13]

The shedding frequency in these cats was found to be low (<30% of all samples positive) in 78%, intermediate (between 30% and 90% of all samples positive) in 21% and high (>90% of all samples positive) in 1% of the cats.

To study viral evolution during chronic infection, the FCoVs sampled from individual cats were characterized. Phylogenetic comparisons of sequences obtained for independent European and American isolates indicated that the viruses in the breeding facility form a clade (a closely related cluster) and are likely to have originated from a single founder infection. Each cat harboured distinct FCoV quasispecies with immune selection (antigenic drift) occurring during chronic infection.

These data support a model in which chronic carriers maintain the endemic infections in cat societies. Virtually every kitten born in a breeding facility becomes infected, probably from its queen[1], as soon as its maternal protection wanes. Once infected, the cats appear to resist superinfection by closely related FCoVs, every cat carrying its private, harmless clan of variants.

At the 1997 WSAVA/BSAVA Congress in Birmingham, workers from Bristol University first presented data that confirmed this epidemiologic concept using a different approach. These workers were indeed able to culture FCoVs from the blood of healthy cats from seropositive catteries. Blood samples obtained from healthy cats of nine different breeds from nine separate catteries were examined, and growth of FCoV, demonstrable by PCR, was obtained in most cases, some of which were FCoV antibody-negative. The conclusion reached was again: most healthy cats living in catteries with a past history of FIP are persistently infected with FcoVs [6]. The important finding of this biologically meaningful analysis was that the isolated viruses were of the 'non-cultivable' subtype I.

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