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PubMed2003

Shifts in circulating lymphocyte subsets in cats with feline infectious peritonitis (FIP): pathogenic role and diagnostic relevance.

Cats with feline infectious peritonitis (FIP) are usually lymphopenic and have lymphoid depletion evident in spleen and lymph nodes. In particular, the number of CD4+ lymphocytes in tissues decreases during the evolution of FIP lesions. This decrease is most likely due to increased lymphocyte apoptotic rate. In contrast, cats infected with the Feline Coronavirus (FCoV) develop a follicular hyperplasia in the peripheral lymph nodes. The current study was devised to evaluate the possible pathogenic role of shifts in circulating lymphocyte subsets in FIP. Peripheral blood from cats with FIP was evaluated and compared with peripheral blood from clinically healthy cats living in both FCoV-free and FCoV-endemic catteries. Blood from cats with diseases other than FIP was also examined in order to define the diagnostic relevance of the changes. Lymphocyte subsets were analysed by flow cytometry, using a whole blood indirect immunofluorescence technique and mAbs specific for feline CD5, CD4, CD8, CD21. The results of the current study suggest that cats recently infected with FCoV that do not develop the disease have a transient increase in T cells; cats from groups with high prevalence of FIP have a moderate but persistent decrease in T cell subsets; cats with FIP have a very severe decrease in all the subsets of lymphocytes. Moreover, during FIP many lymphocytes do not express any membrane antigen, most likely due to early apoptosis. Cats with diseases other than FIP also had decreased number of lymphocytes: as a consequence, the diagnostic relevance of these findings is very low. Nevertheless, the lack of flow cytometric changes had a high negative predictive value (NPV), thus allowing to exclude FIP from the list of possible diagnoses in cats with normal cytograms.

Animals↗

PubMed1993

A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and vaccination.

Feline infectious peritonitis (FIP) has been an elusive and frustrating problem for veterinary practitioners and cat breeders for many years. Over the last several years, reports have begun to elucidate aspects of the molecular biology of the causal virus (FIPV). These papers complement a rapidly growing base of knowledge concerning the molecular organization and replication of coronaviruses in general. The fascinating immunopathogenesis of FIPV infection and the virus' interaction with macrophages has also been the subject of several recent papers. It is now clear that FIPV may be of interest to scientists other than veterinary virologists since its pathogenesis may provide a useful model system for other viruses whose infectivity is enhanced in the presence of virus-specific antibody. With these advances and the recent release of the first commercially-available FIPV vaccine, it is appropriate to review what is known about the organization and replication of coronaviruses and the pathogenesis of FIPV infection.

Animals↗

PubMed1997

Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus.

OBJECTIVE: To determine what risk factors, other than genetic predisposition, contribute to the incidence of feline infectious peritonitis (FIP) in private breeding catteries and animal shelters. DESIGN: Cats from 7 catteries and a shelter were observed monthly for 1 year. At each visit, cats were examined, fecal samples were collected for determination of feline coronavirus shedding, and blood samples were collected for determination of coronavirus antibody titers. Diagnostic tests were performed on all cats that died of FIP. ANIMALS: 275 purebred or random-bred cats that were kept by private breeder-owners in homes. RESULTS: 24 cats died of FIP during the study. Development of FIP was not associated with cattery, mean cat number, mean age, sex, cattery median coronavirus antibody titer, husbandry and quarantine practices, caging and breeding practices, or prevalence of concurrent diseases. However, risk factors for FIP included individual cat age individual cat coronavirus titer, overall frequency of fecal coronarvirus shedding, and the proportion of cats in the cattery that were chronic coronavirus shedders. Deaths from FIP were more frequent in fall and winter, and on the basis of analysis of cattery records, the number of deaths varied yearly. Epidemics (> 10% mortality rate) were reported at least once in 5 years in 4 catteries. CLINICAL IMPLICATIONS: Elimination of FIP from a cattery is only possible by total elimination of endemic feline enteric coronavirus (FECV) infection. The most important procedure to reduce FECV from catteries is elimination of chronic FECV shedders.

Age Factors↗

PubMed1989

Characterization of a temperature sensitive feline infectious peritonitis coronavirus.

The characteristics of a temperature sensitive feline infectious peritonitis virus (TS-FIPV) were examined. TS-FIPV, unlike its parent strain, DF2 wild type FIPV (WT-FIPV), propagated at 31 degrees C (permissive temperature) but not at 39 degrees C (nonpermissive temperature). This temperature preference of TS-FIPV was also demonstrated in cats by the ability of the virus to replicate only at the lower temperature in the upper respiratory tract and not at systemic sites where higher temperatures (38-39 degrees C) prevail. Viral structural proteins and RNA were synthesized at 39 degrees C but some undefined maturational defect prevented the formation of infectious TS-FIPV at its nonpermissive temperature. TS-FIPV was more thermolabile than WT-FIPV which indicated alterations in the structural proteins of TS-FIPV, and a difference in the envelope protein of the two viruses was revealed by Western blot analysis. Plaque assay characterization showed that TS-FIPV produced small plaques in comparison to the large plaques of WT-FIPV. These unique characteristics possessed by TS-FIPV may account for its nonvirulent nature and ability to stimulate protective immune responses in cats.

Animals↗

PubMed2001

Deletions in the 7a ORF of feline coronavirus associated with an epidemic of feline infectious peritonitis.

A population of Persian cats experienced an epidemic of feline infectious peritonitis (FIP) over 2 years. Twelve cases of FIP occurred in litters born during this period. Cats contracting FIP were all genetically related through the sire. Feline coronavirus (FCoV) genomic RNA was detected consistently in this study in biologic samples from adult cats, kittens suffering from FIP, and their siblings. Analysis of viral 7a/7b open reading frame (ORFs) were analyzed and revealed two distinct virus variants circulating in the population, one with an intact 7a ORF and one with two major deletions in the 7a ORF. The 7b ORFs were intact and similar among all virus isolates, although point mutations resulting in amino acid changes were present. The sire was determined to be infected with both variants, and was persistently virus-infected. We speculate the deletion variant arose from the non-deletion variant during viral replication in this population, possibly in the sire.

Amino Acid Sequence↗

PubMed2004

Use of recombinant feline interferon and glucocorticoid in the treatment of feline infectious peritonitis.

A total of 12 clinically ill cats previously diagnosed as feline infectious peritonitis (FIP) were treated with a combination of recombinant feline interferon and glucocorticoid. A complete remission (over 2 years) and a partial remission (2 to 5 months) were observed in four (33.3%) and four (33.3%) cases, respectively. Those that survived for more than 2 years were all older cats (6 to 16 years old) with the effusive form of FIP.

Animals↗

PubMed1989

Comparative features of a coronavirus isolated from a cheetah with feline infectious peritonitis.

A coronavirus which was isolated from a cheetah (Acinonyx jubatus) that succumbed to feline infectious peritonitis was characterized in vitro. The virus was determined to be highly cell-associated with Crandell feline kidney (CrFK) cells and was routinely maintained as a persistent infection (CrFK 83-4497). The cheetah coronavirus was compared with other members of the feline coronavirus group including the feline enteric coronavirus (FECV) 79-1683 and the feline infectious peritonitis viruses (FIPV), 79-1146, and UCD-1. The cheetah coronavirus was demonstrated to have a restricted host-cell range with limited cytopathic effect. Indirect immunofluorescence with antisera to FIPV UCD-1 revealed the concentration of viral antigens in the perinuclear region of cells infected with the cheetah coronavirus. Ultrastructural studies of the cheetah coronavirus indicated a limited number of immature viral particles within cytoplasmic vesicles and at the cell surface. This was in contrast to electron microscopy results of FECV 79-1683 and FIPV 79-1146, which had numerous mature virus particles within the cytoplasmic vesicles, as well as at the cell surface. The cheetah coronavirus was tentatively placed in the feline coronavirus family based upon its antigenic reactivity by immunofluorescence; however, the possibility that it represents a unique coronavirus of cheetahs should not be dismissed without further analyses at the host and genomic levels.

Acinonyx↗

PubMed2003

Vaccine efficacy of a cell lysate with recombinant baculovirus-expressed feline infectious peritonitis (FIP) virus nucleocapsid protein against progression of FIP.

The Type II feline infectious peritonitis virus (FIPV) infection of feline macrophages is enhanced by a monoclonal antibody (MAb) to the S protein of FIPV. This antibody-dependent enhancement (ADE) activity increased with the MAb that showed a neutralizing activity with feline kidney cells, suggesting that there was a distinct correlation between ADE activity and the neutralizing activity. The close association between enhancing and neutralizing epitopes is an obstacle to developing a vaccine containing only neutralizing epitopes without enhancing epitopes. In this study, we immunized cats with cell lysate with recombinant baculovirus-expressed N protein of the Type I FIPV strain KU-2 with an adjuvant and investigated its preventive effect on the progression of FIP. Cats immunized with this vaccine produced antibodies against FIPV virion-derived N protein but did not produce virus-neutralizing antibodies. A delayed type hypersensitivity skin response to N protein was observed in these vaccinated cats, showing that cell mediated immunity against the FIPV antigen was induced. When these vaccinated cats were challenged with a high dose of heterologous FIPV, the survival rate was 75% (6/8), while the survival rate in the control group immunized with SF-9 cell-derived antigen was 12.5% (1/8). This study showed that immunization with the cell lysate with baculovirus-expressed N protein was effective in preventing the progression of FIP without inducing ADE of FIPV infection in cats.

Animals↗

PubMed1988

Effect of diethylcarbamazine on serum antibodies to feline infectious peritonitis in cats.

In preceding studies by the author, use of the immunomodulator drug diethylcarbamazine resulted in the detection of antibodies to feline oncornavirus-associated cell membrane antigen in nine feline leukaemia virus infected cats that had previously given negative results to this antibody. In the present report, seven diethylcarbamazine-treated cats developed higher serum antibody titres to feline infectious peritonitis more frequently than did seven untreated controls. Since feline infectious peritonitis is caused by a coronavirus, these results suggest that diethylcarbamazine treatment could be exploited for vaccination and treatment strategies for non-retroviral in addition to retroviral infections.

Animals↗

PubMed1996

Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with a feline enteric coronavirus.

Two groups of cats were experimentally infected orally with the cat-passaged RM strain of feline enteric coronavirus (FECV-RM). One group of cats (n = 19) had been chronically infected with feline immunodeficiency virus (FIV) for over 6 years, while a second control group (n = 20) consisted of FIV-naive siblings. Fecal virus shedding of FECV occurred in both groups starting on day 3 postinfection, nearly ceased by 4 weeks in FIV-uninfected cats, but remained at high levels in FIV-infected animals. FIV-infected cats shed virus for a longer period of time and at levels 10 to 100 times greater than those for FIV-uninfected cats. The coronavirus antibody response of the FIV-infected cats was delayed and of reduced titer compared with that of the FIV-uninfected animals. Cats in both groups remained asymptomatic for the first two months following FECV-RM infection; however, 8 to 10 weeks postinfection two cats in the FIV-infected group developed feline infectious peritonitis (FIP). The FIP viruses (designated FIPV-UCD9 and -UCD10) isolated from these two cats had almost complete genetic homology to each other and to the infecting FECV-RM. However, unlike FECV-RM, they readily induced FIP when inoculated intraperitoneally into specific-pathogen-free cats. This study confirms that FIPVs are frequently and rapidly arising mutants of FECV. Immunosuppression caused by chronic FIV infection may have enhanced the creation and selection of FIPV mutants by increasing the rate of FECV replication in the bowel and inhibiting the host's ability to combat the mutant viruses once they occurred.

Animals↗

PubMed2005

Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990-2002).

OBJECTIVES: To review the clinicopathological findings in naturally-occurring, histopathologically confirmed cases of feline infectious peritonitis in client-owned cats in Sydney, Australia, with the purpose of identifying factors assisting in the diagnosis of this complex disease syndrome and to characterise the disease as it occurs in this region. DESIGN: Retrospective clinical study: the clinical records of all cats with histopathologically confirmed feline infectious peritonitis at the University Veterinary Centre Sydney and a private cat hospital in Sydney between 1990 and 2002 were reviewed for signalment, history, physical findings, diagnostic test results and the distribution of histological lesions throughout the body at necropsy. RESULTS: Forty-two cats met the inclusion criteria. Significant features of this study that unique to the contemporary literature are i) the over-representation of certain breeds (Burmese, Australian Mist, British Shorthaired, and Cornish Rex) and the under-representation of other breeds (Domestic Shorthaired, Persian); ii) the overrepresentation of males; iii) the tendency for effusive disease in Australian Mist cats and non-effusive disease in Burmese; iv) the even age distribution of disease seen in cats older than 2 years-of-age; and v) the presence of fulminant immune-mediated haemolytic anaemia in two cats in this study. CONCLUSION: The study highlights the diverse range of clinical manifestations and the complexities experienced by clinicians in diagnosing this fatal disease. Some aspects of the epidemiology and clinical manifestations of feline infectious peritonitis appear different to the disease encountered in Europe and North America, most notably the over-representation of specific breeds and the presence of immune-mediated haemolytic anaemia.

Age Factors↗

PubMed2005

Identification of a feline coronavirus type I strain from a cat with feline infectious peritonitis by RT-pCR and phylogenetic analysis.

A case of feline infectious peritonitis (FIP) in an 11-month-old European shorthair cat is reported. The infected cat displayed loss of weight, respiratory distress, ascitis, anemia and died within 15 days after the first appearance of clinical signs. Lesions typical of a mixed form (effusive and non-effusive) of FIP were observed and by RT-PCR a feline coronavirus (FCoV) type I strain was detected in several tissues. The RT-PCR results were confirmed by sequence analysis of the amplified products. Phylogeny carried out on fragments of the M and S genes showed that the FCoV strain segregates with typical type I FCoVs.

Animals↗

PubMed1992

Monoclonal antibody analysis of neutralization and antibody-dependent enhancement of feline infectious peritonitis virus.

Fifty-four monoclonal antibodies (MAbs) to feline infectious peritonitis virus (FIPV) were characterized according to protein specificity, immunoglobulin subclass, virus neutralization, reactivity with different coronaviruses, and ability to induce antibody-dependent enhancement (ADE) of FIPV infection in vitro. The MAbs were found to be specific for one of three structural proteins of FIPV. A total of 47 MAbs were specific for the 205-kDa spike protein (S), 3 MAbs were specific for the 45-kDa nucleocapsid protein (N), and 4 MAbs were specific for the 26- to 28-kDa membrane protein (M). The S-specific MAbs showed various degrees of cross-reactivity with strains of FIPV, feline enteric coronavirus, canine coronavirus, and porcine transmissible gastroenteritis virus. Nineteen S-specific MAbs neutralized FIPV. A total of 15 of the neutralizing MAbs induced ADE, and all but 1 were of the immunoglobulin G2a subclass. The remaining four neutralizing MAbs that did not induce ADE were of the immunoglobulin G1 subclass. Two S-specific MAbs induced ADE but were nonneutralizing. None of the N- or M-specific MAbs was neutralizing or induced ADE. On the basis of the reactivity patterns of the MAbs with FIPV and related coronaviruses, it was concluded that there is a minimum of five neutralizing sites on S. In most instances, neutralizing MAbs were able to induce ADE, demonstrating a direct relationship between neutralization and enhancement. The difference in immunoglobulin subclass between neutralizing MAbs that induced ADE and those that did not induce ADE suggests that there may be a restriction in the immunoglobulin subclasses capable of mediating ADE.

Animals↗

PubMed1981

Infection studies in kittens, using feline infectious peritonitis virus propagated in cell culture.

The propagation of feline infectious peritonitis virus (NW1-FIPV strain) in cell culture is described. Tissue culture-propagated virus was used to inoculate specific-pathogen-free kittens intraperitoneally, intratracheally, or orally. Intraperitoneal inoculation caused seroconversion and effusive peritonitis in 100% of the kittens. Intratracheal inoculation produced disease in 60% of the kittens, and oral inoculation in only 20%. Seroconversions without production of disease occurred in 10% of the kittens inoculated by either the intratracheal or the oral route. The remainder of the kittens inoculated by the intratracheal (30%) and oral (70%) routes did not develop serum antibodies or disease.

Administration, Oral↗

PubMed1992

Immunization of cats against feline infectious peritonitis with anti-idiotypic antibodies.

Anti-idiotypic antibodies (Ab2s) generated against neutralizing antibodies (Ab1s) specific for feline infectious peritonitis virus (FIPV) were shown to be specific for paratope-associated idiotopes of the Ab1s and not against isotypic determinants. In a study to determine the efficacy of an anti-idiotypic vaccine against feline infectious peritonitis (FIP), cats that were immunized with a pool of monoclonal Ab2s developed Ab3s that recognized the variable regions of the Ab2s as well as the natural antigen. In cats challenged with a lethal dose of virus the control group followed a predictable course of infection ultimately succumbing to FIP. Two immunized cats survived virus challenge and a third cat lived twice as long as the controls. The fourth immunized cat showed no evidence of protection. The ability to induce levels of protection against FIP lends support to the concept of using anti-idiotypic antibodies as a prophylactic vaccine.

Animals↗

PubMedDate not supplied

Comparison of different tests to diagnose feline infectious peritonitis.

Clinical data from 488 cats (1979-2000) with histopathologically confirmed feline infectious peritonitis (FIP) and 620 comparable controls were evaluated retrospectively to assess the value of several diagnostic tests frequently used in the evaluation of cats with suspected FIP. Diagnostic utility of serum albumin to globulin ratio for the diagnosis of FIP was greater than of the utility of serum total protein and gamma-globulin concentrations. Diagnostic utility of these variables was higher when performed on effusion. On effusion, positive and negative predictive values of Rivalta's test, a test that distinguishes between exudates and transudates (0.86 and 0.97), anti-coronavirus antibody detection (0.90 and 0.79), and immunofluorescence staining of coronavirus antigen in macrophages (1.00 and 0.57) were investigated. The positive and negative predictive values of presence of anti-coronavirus antibodies were 0.44 and 0.90, respectively, antibody concentrations (1:1,600) were 0.94 and 0.88. presence of immune complexes measured by a competitive enzyme-linked immunosorbent assay were 0.67 and 0.84, and detection of viral RNA by serum reverse-transcriptase polymerase chain reaction (RT-PCR) were 0.90 and 0.47. Effusion RT-PCR was performed in 6 cats; it was positive in all 5 cats with FIP and negative in the cat with another disease. Diagnostic assays on the fluid in cats with body effusion had good predictive values. Definitive diagnosis of FIP on the basis of measurement of various variables in serum was not possible. Serum tests can only be used to facilitate the decision for more invasive diagnostic methods.

Animals↗

PubMed2005

Sensitivity of Tru-cut and fine needle aspiration biopsies of liver and kidney for diagnosis of feline infectious peritonitis.

BACKGROUND: The detection of typical lesions and feline coronavirus (FCoV) antigen in tissues is the only conclusive method for making a diagnosis of feline infectious peritonitis (FIP). A positive result using Tru-cut biopsy (TCB) and fine-needle aspiration biopsy (FNAB) has high diagnostic specificity, but information about the capacity of these techniques to correctly identify cats with FIP lesions is not available. OBJECTIVES: The diagnostic sensitivity of TCB and FNAB for detecting liver and kidney histologic lesions caused by FIP was evaluated. METHODS: TCB and FNAB specimens collected mainly at necropsy from 25 cats with FIP were analyzed. Diagnostic sensitivity was calculated on the basis of the number of false-negative and true-positive specimens, compared with the number of organs bearing histologic lesions of FIP. RESULTS: Diagnostic sensitivity was higher for hepatic TCB (64%) and FNAB (82%) than for renal (39% and 42%, respectively) procedures. A high percentage of renal cytologic and TCB specimens were inadequate. Combined analysis of TCB and FNAB specimens collected from the same organ increased the diagnostic sensitivity for liver (86%) and kidney (48%). The sensitivity of immunohistochemical/cytochemical analysis was low (11-38% depending on the technique), probably due to variable distribution of feline coronavirus in the lesions. CONCLUSION: Biopsy of liver and kidney can correctly identify FIP lesions. However, false-negative results or inadequate samples occur with moderate frequency, especially for immunochemical analysis. Diagnostic sensitivity may be increased when both TCB and FNAB specimens from the same organ are examined.

Animals↗

PubMed1987

Virologic and immunologic aspects of feline infectious peritonitis virus infection.

A number of feline coronavirus isolates have been characterized over the last few years. These isolates consist of what we have referred to as feline enteric coronaviruses (FECVs) and feline infectious peritonitis viruses (FIPVs). FECVs cause a transient enteritis in kittens but no systemic illness. FIPVs, in contrast, cause a systemic and usually fatal disease syndrome characterized either by an exudative serositis or a disseminated granulomatous disease. Although the diseases they cause are quite different, FECVs and FIPVs are antigenically and morphologically indistinguishable from each other. FECVs have a strict tropism for mature intestinal epithelial cells and do not appear to replicate in macrophages. In contrast, FIPVs, appear to spread rapidly from the intestinal mucosa and replicate in macrophages. Experiments will be presented, and literature cited, that will allow us to make the following assumptions about the pathogenesis of FIPV infection: 1) FIPVs and FECVs represent a spectrum of viruses that differ only in infectivity (ability to evoke seroconversion following oral infection) and virulence (ability to cause FIP), 2) field isolates are generally nearer to FECVs in behavior than laboratory isolates made from animal passaged material, 3) immunity to FIPV appears to be of the premunition type and is maintained for as long as the infection persists in a reactivatable form, 4) strains of feline coronaviruses that do not cause systemic disease, such as FECVs or low virulence FIPVs, can actually sensitize cats to infection with virulent FIPV strains, 5) FeLV infection interferes with established FIP immunity and allows for the reactivation of disease in healthy carriers, 6) FIPV may be passaged from queen to kitten either in utero or during neonatal life, and 7) kittens infected by their mothers with FIPV do not usually develop FIP but become immune carriers of the virus for a period of 5-6 months; recovery from the carrier state is associated with a loss of premunition immunity.

Animals↗