Retrospective Survival Analysis of Cats with Feline Infectious Peritonitis Treated with Polyprenyl Immunostimulant That Survived over 365 Days.

Feline infectious peritonitis (FIP) remains a major diagnostic and treatment challenge in feline medicine. An ineffective immune response is an important component of FIP pathophysiology; hence treatment with an immune stimulant such as Polyprenyl Immunostimulant™ (PI), which enhances cell-mediated immunity by upregulating the innate immune response via Toll-like receptors, is a rational approach. Records of cats with FIP treated with PI orally for over 365 days were retrospectively studied. Of these cats (n = 174), records were obtained for n = 103 cats with appropriate clinical signs and clinical pathology. Of these, n = 29 had FIP confirmed by immunohistochemistry (IHC) or reverse transcription polymerase-chain-reaction (RT-PCR). Most of the cats (25/29; 86%) had non-effusive FIP, and only 4/29 cats (14%) had effusive FIP. The mean survival time (MST) was 2927 days (eight years); with 55% of the cats (16/29) still being alive at the time data collection, and 45% (13/29) having died. A persistently low hematocrit plus low albumin:globulin (A:G) ratio, despite treatment, was a negative prognostic indicator. It took a mean of ~182 days and ~375 days, respectively, for anemia and low A:G ratio to resolve in the cats that presented with these laboratory changes. This study shows that PI is beneficial in the treatment of FIP, and more studies are needed to establish the best protocols of use.

Retroperitoneal pyogranulomatous and fibrosing inflammation secondary to fungal infections in two dogs.

CASE DESCRIPTIONS: A 4-year-old spayed female Golden Retriever (dog 1) was examined because of acute edema and erythema in the left hind limb and an inguinal mass, and a 5-year-old female Jack Russell Terrier (dog 2) was examined because of a recurring retro-peritoneal mass. CLINICAL FINDINGS: Dog 1 had an edematous, hyperemic left hind limb with a fixed inguinal mass. Monocytic neutrophilic leukocytosis and hypoalbuminemia were detected. Diagnostic imaging revealed abnormal tissue surrounding the larger vessels and ureters and complete occlusion of the left limb veins. Surgery resulted in incomplete removal of the mass. Histologic examination revealed fibrosing pyogranulomatous inflammation. Results of a Histoplasma antigen test were positive, and reanalysis of the tissues revealed yeast cells indicative of Histoplasma capsulatum. Dog 2 had incomplete removal of a retroperitoneal mass. Histologic examination revealed fibrosing pyogranulomatous inflammation. The mass recurred 8 months later in dog 2; exploratory abdominal surgery at that time resulted in substantial hemorrhage from the adhered caudal aorta. Histologic examination of tissue sections from the second surgery revealed yeast cells consistent with Blastomyces dermatitidis. TREATMENT AND OUTCOME: Both dogs had temporary improvement after surgery. Full clinical resolution required treatment for fungal disease. Dog 1 was treated with itraconazole, then fluconazole (total treatment time, 23 weeks). Dog 2 was treated with fluconazole for 36 weeks. CLINICAL RELEVANCE: Retroperitoneal pyogranulomatous fibrosis caused by fungal infections has not been reported in veterinary medicine. There was substantial morbidity, but the prognosis can be good when this abnormality is recognized and antifungal medications are administered.

Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors.

OBJECTIVE: To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment. ANIMALS: 132 dogs with nonresectable grade 2 or 3 MCTs. PROCEDURES: Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time. RESULTS: In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib. CONCLUSIONS AND CLINICAL RELEVANCE: Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs.

Effect of Polyprenyl Immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis.

Feline infectious peritonitis (FIP) is considered a fatal disease. Three cats with dry form FIP were treated with Polyprenyl Immunostimulant. Two of the three cats are still on treatment and are alive and well 2 years after diagnosis. The third cat survived 14 months but was treated for only 4.5 months. Further studies are necessary to assess the potential of the Polyprenyl Immunostimulant.

Molecular characterisation of canine nonsteroidal anti-inflammatory drug-activated gene (NAG-1).

Nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1), a divergent member of the transforming growth factor beta superfamily, was previously identified as a gene induced by several anti-tumorigenic compounds, including NSAIDs and peroxisome proliferator-activated receptor gamma (PPARgamma) ligands in humans. In this study, canine NAG-1 was characterised from a canine genomic database. Gene induction by some NSAIDs and PPARgamma ligands was demonstrated in canine osteosarcoma cell lines. Phylogenetic analysis indicates that canine NAG-1 is more homologous with the corresponding mouse and rat genes than with human NAG-1. Expression of canine NAG-1 was increased by treatment with piroxicam and SC-560 (NSAIDs) and the PPARgamma ligand rosiglitazone. This study demonstrates that canine NAG-1 is up-regulated by some anti-tumorigenic compounds in osteosarcoma cell lines and may provide an important target of chemotherapy in canine cancer.

Long-Term Treatment and Survival in Three Apparently Immunocompetent Dogs with Disseminated Fungal Infection Caused by Phialosimplex caninus.

Disseminated fungal infections cause morbidity and mortality in dogs. The prognosis varies depending on the infecting agent. Phialosimplex caninus is a recently recognized type of hyalohyphomyces. Knowledge regarding the clinical course of P caninus infection in dogs is limited to two previous case reports. The clinical features, diagnostic findings, responses to medical therapy, and long-term outcomes of three dogs with disseminated P caninus are presented in this study. All dogs had improved quality of life once itraconazole administration, with or without terbinafine, was instituted. Long-term disease remission was maintained even after discontinuation of antifungal therapy in a single dog.

Cerebral Blastomyces dermatitidis infection in a cat.

CASE DESCRIPTION: An 8-year-old domestic shorthair cat was evaluated because of signs of depression, circling, and visual deficits. CLINICAL FINDINGS: The cat had no cutaneous lesions, and results of an ophthalmologic examination and thoracic radiography were within reference limits. Computed tomography of the brain revealed a mass lesion involving the right parietal, temporal, and occipital lobes; the mass was in broad-based contact with the skull and smoothly marginated and had strong homogenous enhancement after contrast agent administration. During craniectomy, samples of the mass were collected for cytologic and histopathologic evaluations and microbial culture. A diagnosis of Blastomyces dermatitidis-associated meningoencephalitis with secondary pyogranulomatous inflammation was made. TREATMENT AND OUTCOME: Amphotericin B (0.25 mg/kg [0.11 mg/lb], IV) was administered on alternate days (cumulative dose, 1.75 mg/kg [0.8 mg/lb]). To minimize the risk of nephrotoxicosis, assessments of serum biochemical variables (urea nitrogen and creatinine concentrations) and urinalyses were performed at intervals. The third dose of amphotericin B was postponed 48 hours because the cat became azotemic. The cat subsequently received fluconazole (10 mg/kg [4.5 mg/lb], PO, q 12 h) for 5.5 months. Six months after discontinuation of that treatment, the cat appeared healthy and had no signs of relapse. CLINICAL RELEVANCE: Brain infection with B dermatitidis is typically associated with widespread disseminated disease. The cat of this report had no evidence of systemic disease. Blastomycosis of the CNS should be considered as a differential diagnosis for brain lesions in cats from areas in which B dermatitidis is endemic.

Transduction of hematopoietic stem cells to stimulate RNA interference against feline infectious peritonitis.

Objectives The goals of the study were: (1) to develop and evaluate non-replicating lentivirus vectors coding for feline coronavirus (FCoV)-specific micro (mi)RNA as a potential antiviral therapy for feline infectious peritonitis (FIP); (2) to assess the feasibility of transducing hematopoietic stem cells (HSCs) with ex vivo introduction of the miRNA-expressing lentivirus vector; and (3) to assess the ability of the expressed miRNA to inhibit FCoV replication in HSCs in vitro. Methods HSCs were obtained from feline bone marrow and replicated in vitro. Three lentiviruses were constructed, each expressing a different anti-FCoV miRNA. HSCs were stably transduced with the miRNA-expressing lentivirus vector that produced the most effective viral inhibition in a feline cell line. The effectiveness of the transduction and the expression of anti-FCoV miRNA were tested by infecting the HSCs with two different strains of FCoV. The inhibition of coronavirus replication was determined by relative quantification of the inhibition of intracellular viral genomic RNA synthesis using real-time, reverse-transcription PCR. The assessment of virus replication inhibition was determined via titration of extracellular virus using the TCID50 assay. Results Inhibition of FCoV was most significant in feline cells expressing miRNA-L2 that targeted the viral leader sequence, 48 h postinfection. miRNA-L2 expression in stably transduced HSCs resulted in 90% and 92% reductions in FIPV WSU 79-1146 genomic RNA synthesis and extracellular virus production, respectively, as well as 74% and 80% reduction in FECV WSU 79-1683 genomic RNA synthesis and extracellular virus production, respectively, as compared with an infected negative control sample producing non-targeting miRNA. Conclusions and relevance These preliminary results show that genetic modification of HSCs for constitutive production of anti-coronavirus miRNA will reduce FCoV replication.

Polyprenyl Immunostimulant in Feline Rhinotracheitis: Randomized Placebo-Controlled Experimental and Field Safety Studies.

Feline rhinotracheitis is a ubiquitous disease caused by feline herpesvirus type 1 (FHV-1). The disease is easily transmissible and common in multi-cat environments where even vaccinated cats can develop clinical signs of respiratory or ocular disease or both when exposed to the virus. Prior to the work reported here, there was no licensed treatment for the disease on the market. We hypothesized that polyprenyl immunostimulant (PI), an immunomodulatory veterinary biologic, would be useful in treating feline rhinotracheitis by reducing the severity of respiratory or/and ocular disease. We conducted double-blinded, randomized, placebo-controlled clinical trials in experimentally infected cats to establish the efficacy of PI. Specific pathogen-free cats were administered a placebo (n = 20) or PI (n = 20) starting on the day of FHV-1 experimental challenge. Trained, masked observers applied a standardized scoring system daily in clinical examinations for 14 days after the FHV-1 challenge. The cats treated with PI had significantly lower disease severity scores over the course of the experiment compared to the cats in the placebo group (p = 0.05). The safety studies, including a field safety study involving 390 owned cats in 10 states, showed that PI was safe to use in cats as young as 8 weeks of age.

Polyprenyl Immunostimulant Treatment of Cats with Presumptive Non-Effusive Feline Infectious Peritonitis In a Field Study.

Feline infectious peritonitis (FIP) is a fatal disease with no clinically effective treatment. This field study evaluated treatment with Polyprenyl Immunostimulant (PI) in cats with the non-effusive form of FIP. Because immune suppression is a major component in the pathology of FIP, we hypothesized that treatment with an immune system stimulant would increase survival times of cats with dry FIP. Sixty cats, diagnosed with dry FIP by primary care and specialist veterinarians and meeting the acceptance criteria, were treated with PI without intentional selection of less severe cases. The survival time from the start of PI treatment in cats diagnosed with dry FIP showed that of the 60 cats with dry FIP treated with PI, 8 survived over 200 days, and 4 of 60 survived over 300 days. A literature search identified 59 cats with non-effusive or dry FIP; no cat with only dry FIP lived longer than 200 days. Veterinarians of cats treated with PI that survived over 30 days reported improvements in clinical signs and behavior. The survival times in our study were significantly longer in cats who were not treated with corticosteroids concurrently with PI. While not a cure, PI shows promise in the treatment of dry form FIP, but a controlled study will be needed to verify the benefit.

Cardiovascular involvement in 8 dogs with blastomyces dermatitidis infection.

BACKGROUND: Blastomycosis is a common systemic fungal infection in dogs. HYPOTHESIS: Dogs with cardiovascular involvement may have abnormalities in electrical conduction and valvular function, and may have a worse prognosis. ANIMALS: Eight client-owned animals. METHODS: Dogs with cardiovascular lesions caused by blastomycosis were identified from retrospective evaluation of medical records. RESULTS: Five dogs had de novo infections and 3 had recurrences of previously treated infections. Harsh labored breathing, lethargy, and anorexia were the most common historic complaints. Three dogs had syncope. Physical examination and clinicopathologic data were typical of blastomycosis and included dyspnea, increased lung sounds, and lethargy. In addition, 3 dogs had heart murmurs and 1 had a third-degree atrioventricular block. Four dogs had myocarditis and 2 had pericarditis or epicarditis. Two dogs had cardiac signs attributed to extracardiac compression by fungal granulomas and clinical signs were relieved by treatment. Half of the remaining 6 dogs were euthanized; 2 of these were not treated. Of the remaining 3 dogs, 1 dog died acutely while sleeping; the second died intraoperatively during an attempt to place an epicardial pacemaker; and the third had Blastomyces-induced endocarditis and died of heart failure. CONCLUSIONS AND CLINICAL IMPORTANCE: Blastomycosis should be considered in the differential diagnosis of dogs from endemic areas with inflammatory myocarditis, heart block, heart base or intracardiac mass lesions, syncope, or endocarditis.

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

OBJECTIVE: To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. ANIMALS: 5 healthy purpose-bred hounds. PROCEDURES: The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. RESULTS: Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

Characterization of uptake of 2-deoxy-2-[18F]fluoro-D-glucose by fungal-associated inflammation: the differential uptake ratio for blastomyces-associated lesions is as high as for lymphoma and higher than for turpentine abscesses in experimentally induced lesions in rats.

PURPOSE: The objective of this investigation was to determine the biologic basis and the significance of uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) using experimentally created fungal lesions in rats. PROCEDURES: Uptake of FDG by experimentally induced Blastomyces granulomas was compared with uptake by turpentine abscesses (Group 1) and by lymphomas (Group 2) using the differential uptake ratio (DUR) measured one hour after administration of 2 mCi FDG intravenously. Frozen tissue sections of Blastomyces lesions and turpentine abscesses were placed in contact with radiographic film for macroautoradiography. RESULTS: In rats in Group 1, the median (range) DUR for the Blastomyces granulomas was 1.9 (1.1-2.6) and was significantly higher than the DUR for turpentine abscesses 0.9 (0.6-1.4) and muscle 0.2 (0.1-0.5; P < 0.001). In Group 2, the median (range) DUR for the Blastomyces granulomas, lymphomas, and muscle from the rats in Group 2 were 1.8 (1.2-3.4), 1.9 (1.0-4.0), and 0.2 (0.1-0.3), respectively. There was no significant difference between the DUR of Blastomyces granulomas and lymphomas. Macroautoradiographs of the Blastomyces granulomas revealed intense uptake of FDG in the region occupied by the yeast organisms and the granulomatous inflammation. CONCLUSIONS: Blastomyces granulomas typically have high uptake of FDG associated with the region composed of the granulomatous inflammatory reaction and Blastomyces yeast organisms.

Characterization of uptake of 2-deoxy-2-[18F] fluoro-D-glucose by fungal-associated inflammation: the standardized uptake value is greater for lesions of blastomycosis than for lymphoma in dogs with naturally occurring disease.

PURPOSE: Based on limited reports, fungal lesions can have remarkably high intensity uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) on positron emission tomography (PET) images. The purpose of this investigation was to compare the standardized uptake value (SUV) of naturally occurring lesions of blastomycosis with the SUV of naturally occurring lymphoma in a series of dogs. PROCEDURES: Five dogs with naturally occurring blastomycosis and three dogs with lymphoma underwent whole-body FDG-PET prior to receiving any treatment for their disease. RESULTS: The (mean +/- SD) SUV for 13 blastomycosis lesions was 7.7 +/- 2.0 versus a mean for 17 lymphomas of 4.8 +/- 1.8. These values were significantly different (P = 0.0537). There was overlap between the SUV of Blastomyces-associated lesions versus lymphomas, but a cut-off SUV of 7.0 was 100% specific for Blastomyces lesions. Numerous sites of disease were detected on the FDG-PET images that were not detected clinically. CONCLUSIONS: FDG-PET is useful for determining the extent of disease in dogs with blastomycosis. The SUV for Blastomyces-associated lesions are as high or higher than for malignant lymphoma. Due to the similarities in canine and human blastomycosis and lymphomas, similar results would be predicted in human patients. In regions where blastomycosis is endemic, Blastomyces granulomas should be considered a differential diagnosis for lesions with high intensity uptake of FDG.

Blastomyces dermatitidis produces melanin in vitro and during infection.

Melanin is made by several important pathogenic fungi and is implicated in the pathogenesis of a number of mycoses. This study investigates whether the thermally dimorphic fungal pathogen Blastomyces dermatitidis produces melanin. Using techniques developed to study melanization in other fungi, we demonstrate that B. dermatitidis conidia and yeast produce melanin in vitro and that yeast cells synthesize melanin or melanin-like pigment in vivo. Melanization reduced susceptibility to amphotericin B, but not to itraconazole or voriconazole. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may affect the pathogenesis of blastomycosis.

Prevalence of infectious diseases in feral cats in Northern Florida.

Objectives of this study were to determine prevalence of infection in feral cats in Northern Florida with a select group of infectious organisms and to determine risk factors for infection. Blood samples or sera from 553 cats were tested with a panel of antibody, antigen or PCR assays. Male cats were at higher risk for FIV, Mycoplasma haemofelis, and M. haemominutum. Infection with either FeLV or FIV was associated with increased risk for coinfection with the other retrovirus, M. haemofelis, or M. haemominutum. Bartonella henselae had the highest prevalence and was the only organism that did not have any associated risk for coinfection with other organisms. Feral cats in this study had similar or lower prevalence rates of infections than those published for pet cats in the United States. Thus, feral cats assessed in this study appear to be of no greater risk to human beings or other cats than pet cats.

Comparison of results for serologic testing and a polymerase chain reaction assay to determine the prevalence of stray dogs in eastern Tennessee seropositive to Ehrlichia canis.

OBJECTIVE: To determine the prevalence of stray dogs in eastern Tennessee seropositive to Ehrlichia canis and examine the correlation between results for an ELISA, indirect immunofluorescent antibody (IFA) test, and polymerase chain reaction (PCR) assay. SAMPLE POPULATION: Blood samples obtained from 90 adult dogs admitted to an animal shelter in eastern Tennessee. PROCEDURE: Serum samples were analyzed for antibodies against E. canis by use of a commercially available ELISA kit, 2 IFA tests, and a PCR assay; testing was performed at the University of Tennessee (TN) and North Carolina State University (NCSU). The PCR amplification was performed by use of DNA extracted from EDTA-anticoagulated blood and primers designed to amplify DNA of Ehrlichia spp. RESULTS: Antibodies against E. canis were detected in only 1 dog by use of the ELISA. By IFA testing at TN, 10 of 90 (11%) dogs were seroreactive against E. canis antigens, all of which had medium to high titers to E. canis. Only 5 of the 10 TN seroreactors were also reactive against E. canis antigens in IFA tests conducted at NCSU, and all 5 had low to medium titers. The DNA of Ehrlichia spp was not amplified in any blood samples by use of PCR assays conducted at the TN or NCSU. CONCLUSIONS AND CLINICAL RELEVANCE: The discordant ELISA, IFA, and PCR results obtained in this study were unexpected and may have been related to exposure of dogs to an Ehrlichia species other than E. canis, such as E. ewingii.

Photodynamic therapy response in cats with cutaneous squamous cell carcinoma as a function of fluence.

The response of advanced stage cutaneous squamous cell carcinomas (SCC) following treatment with photodynamic therapy (PDT) has been poor. It was the aim of this pilot study to determine whether an increase in the delivered fluence (i.e. energy density) would improve the duration of tumour remission in cats with advanced-stage SCC. Tumours were treated with aluminium phthalocyanine tetrasulphonate (AlPcS4 ) PDT at a fluence of either 100 J cm-2 or 200 J cm-2 and tumour response was evaluated at regular intervals. Those feline tumours treated with a fluence of 100 J cm-2 (n= 8) had a significantly shorter median remission duration (69 days; range 0-619 days) than those feline tumours treated with 200 J cm-2 (n= 6; 522 days; range 151-1057 days). It is our conclusion that a fluence of 200 J cm-2 is well tolerated and more effective when treating cats with advanced stage cutaneous SCC.

Effect of small interfering RNAs on in vitro replication and gene expression of feline coronavirus.

OBJECTIVE: To evaluate the ability of small interfering RNAs (siRNAs) to inhibit in vitro viral replication and gene expression of feline coronavirus (FCoV). SAMPLE: Cell cultures of Crandell-Rees feline kidney cells. PROCEDURES: 5 synthetic siRNAs that each targeted a different region of the FCoV genome were tested individually and in various combinations for their antiviral effects against 2 strains of FCoV (feline infectious peritonitis virus WSU 79-1146 and feline enteric coronavirus WSU 79-1683) in cell cultures. Tested combinations targeted the FCoV leader and 3' untranslated region, FCoV leader region and nucleocapsid gene, and FCoV leader region, 3' untranslated region, and nucleocapsid gene. For each test condition, assessments included relative quantification of the inhibition of intracellular viral genomic RNA synthesis by means of real-time, reverse-transcription PCR analysis; flow cytometric evaluation of the reduction of viral protein expression in infected cells; and assessment of virus replication inhibition via titration of extracellular virus with a TCID50 infectivity assay. RESULTS: The 5 siRNAs had variable inhibitory effects on FCoV when used singly. Combinations of siRNAs that targeted different regions of the viral genome resulted in more effective viral inhibition than did individual siRNAs that targeted a single gene. The tested siRNA combinations resulted in approximately 95% reduction in viral replication (based on virus titration results), compared with findings in negative control, nontargeting siRNA-treated, FCoV-infected cells. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro replication of FCoV was specifically inhibited by siRNAs that targeted coding and noncoding regions of the viral genome, suggesting a potential therapeutic application of RNA interference in treatment of feline infectious peritonitis.