Persistence and Evolution of Feline Coronavirus in a Closed Cat-Breeding Colony

Abstract

Feline coronavirus (FCoV) persistence and evolution were studied in a closed cat-breeding facility with an endemic serotype I FCoV infection. Viral RNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the feces and/or plasma of 36 of 42 cats (86%) tested. Of 5 cats, identified as FCoV shedders during the initial survey, 4 had detectable viral RNA in the feces when tested 111 days later. To determine whether this was due to continuous reinfection or to viral persistence, 2 cats were placed in strict isolation and virus shedding in the feces was monitored every 2-4 days. In 1 of the cats, virus shedding continued for up to 7 months. The other animal was sacrificed after 124 days of continuous virus shedding in order to identify the sites of viral replication. Viral mRNA was detected only in the ileum, colon, and rectum. Also in these tissues, FCoV-infected cells were identified by immunohistochemistry. These findings provide the first formal evidence that FCoV causes chronic enteric infections. To assess FCoV heterogeneity in the breeding facility and to study viral evolution during chronic infection, FCoV quasispecies sampled from individual cats were characterized by RT-PCR amplification of selected regions of the viral genome followed by sequence analysis. Phylogenetic comparison of nucleotides 7-146 of ORF7b to corresponding sequences obtained for independent European and American isolates indicated that the viruses in the breeding facility form a clade and are likely to have originated from a single founder infection. Comparative consensus sequence analysis of the more variable region formed by residues 79-478 of the S gene revealed that each cat harbored a distinct FCoV quasispecies. Moreover, FCoV appeared to be subject to immune selection during chronic infection. The combined data support a model in which the endemic infection is maintained by chronically infected carriers. Virtually every cat born to the breeding facility becomes infected, indicating that FCoV is spread very efficiently. FCoV-infected cats, however, appear to resist superinfection by closely related FCoVs.

Comparison of Serologic Techniques for the Detection of Antibodies against Feline Coronaviruses

“…Immune response to FCoV, though inadequate to sterilize the infection (FCoV-specific antibody titers were modest and remained low throughout the chronic infection), is vigorous enough to enforce immune system and to prevent infection by antigenically related FCoVs. To support this observation, a previous study 14 regarding coronavirus epidemiology, persistence, and evolution in a closed cat-breeding facility with an endemic FCoV infection reported that the virus involved was a serotype I strain and that some cats, previously identified as shedders, still had detectable viral RNA in their feces.…”

“…Several authors have demonstrated that the virus persists in the intestine of healthy cats and may be excreted over a period of months or even years. 11,13,14 These cats represent the coronavirus reservoir, and some of them can develop a fatal immune-mediated disease called feline infectious peritonitis (FIP). 8 Since FCoVs are ubiquitous pathogens, the evaluation of anti-FCoV antibodies can be useful to monitor infection in a breeding cattery and/or an FCoV-free household.…”

Diversidade gênica do coronavírus felino em populações virais entéricas e sistêmicas intra e inter-hospedeiros

“…A similar pattern was observed in a previous study that also examined the M gene (CHANG; EGBERINK; ROTTIER, 2011) which determined that FIPVs originate from FECVs by the accumulation and selection of point mutations (POLAND et al, 1996;VENNEMA et al, 1998;PEDERSEN et al, 2009). The internal mutation hypothesis has been widely accepted and is mainly supported by the close similarities between FECoV and FIPV and the low incidence of FIP outbreaks, despite the high proportion of FCoV-seropositive cats (SPARKES; GRUFFYDD-JONES; HERREWEGH et al, 1997;HOLST et al, 2006;PRATELLI, 2008).…”

“…Although no disease-specific clusters of FCoVs were found, samples from Cat 6 were particularly informative, as two different strains of FCoV, one enteric and one systemic, can be clearly observed in Figure 1 Catteries and closed multi-cat environments usually have one major enzootic strain of coronavirus that persists over long periods of time, and these major enzootic strains are dominant even with exposure to other strains (POLAND et al, 1996;HERREWEGH et al, 1997;VENNEMA et al, 1998;ADDIE et al, 2003;PEDERSEN et al, 2009).…”

“…The hypothesis known as the "internal mutation theory" is widely accepted (POLAND et al, 1996;HERREWEGH et al, 1997;VENNEMA et al, 1998;PEDERSEN et al, 2009;CHANG et al, 2010;ROTTIER, 2011), and it states that FIP occurs when a cat is exposed to variants of FCoV that have mutated within the host and are able to disseminate from the gut (the primary site of infection) by gaining the ability to efficiently replicate within the macrophages (POLAND et al, 1996;VENNEMA et al, 1998). However, any stable genetic differences between FECoV and FIPV that can account for their differing pathogenicities remain to be identified (DYE; SIDDELL, 2007).…”