Search Results (44)

Feline coronaviruses (FCoVs) are divided into two groups: feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). FIPV is responsible for the severe disease known as feline infectious peritonitis, while FECV typically causes mild symptoms, such as diarrhea, and often does not lead to any disease at all. Currently, it is not possible to distinguish between FIPV and FECV at the molecular level. Therefore, there is an urgent need to understand the molecular features of FIPV. Here, we generated a recombinant virus by replacing the ORF1ab region and the coding sequence for the spike (S) protein of an FECV with the corresponding sequences from FIPVs. The recombinant virus (recFECV-S_DF-2-1ab_FIPV) exhibited similar growth kinetics to its parental strain. Our analysis revealed that the replacement of the ORF1ab in the FECV caused significant alterations in protein expression within the host cells. Furthermore, the presence of the ORF1ab from the FIPV strain resulted in enhanced suppression of the innate immune response compared to the parental strain, as determined through proteomic and transcriptomic studies. Additionally, we demonstrated that the papain-like protease 2 (PL2^pro) of the non-structural protein 3 (NSP3) from both FIPV and FECV functions in immune suppression, and the protease activity is required for this function. Full article

Feline infectious peritonitis (FIP) is a progressive and often fatal disease caused by a virulent biotype of feline coronavirus (FCoV). Although antiviral treatments are now available, relapse and resistance remain ongoing concerns. This study investigates the therapeutic potential of P. indusiatus, a medicinal mushroom, for its antiviral and anti-inflammatory activities against FIP. The main protease (FIPV M^pro) of feline infectious peritonitis virus (FIPV) was recombinantly expressed and purified to facilitate enzyme inhibition screening. P. indusiatus exhibited the strongest FIPV M^pro inhibitory activity among the 17 mushroom extracts tested (69.2%), showing a notable level of inhibition relative to standard antiviral agents such as lopinavir and ritonavir. To assess its anti-inflammatory potential, PBMCs derived from healthy cats and FIP-associated effusions (FIP fluid) were cultured and stimulated with LPS to induce inflammation. In healthy PBMCs, P. indusiatus significantly reduced nitrite levels, with effects similar to dexamethasone. However, PBMCs from FIP fluid, already in an activated state, showed no additional response. Notably, this study is the first to successfully isolate and culture PBMCs from FIP fluid, providing a new platform for future immunological research. These findings suggest that P. indusiatus possesses both antiviral and anti-inflammatory properties, positioning it as a potential dual-action therapeutic candidate for FIP. Further investigation into cytokine signaling pathways is warranted to clarify its mechanisms of action and advance future therapeutic development. Full article

Feline infectious peritonitis virus (FIPV), caused by a mutated form of feline coronavirus, poses a significant threat to feline health worldwide, with limited therapeutic options available. This study investigated the antiviral potential of α-mangostin (α-MG) and its enriched extracts (AMEs), obtained via microwave-assisted extraction, against FIPV. We evaluated their cytotoxicity, direct virucidal activity, and antiviral activity in CRFK cells. Both α-MG and AMEs demonstrated significant antiviral activity, with EC₅₀ values from 2.71 to 2.88 μg/mL and favorable selectivity indices (3.25–3.66). Notably, AMEs exhibited direct virucidal effects, effectively reducing viral titers. Furthermore, treatment with these compounds significantly reduced inflammatory cytokine expression (IFN-β, TNF-α, and IL-6 mRNA levels) and decreased viral loads in FIPV-infected cells. Drug combination studies using the ZIP model revealed enhanced cooperative effects when AMEs and α-MG were combined with GC-376 or GS-441524, with GC-376 combinations showing particularly strong synergistic potential. These findings suggest that α-MG and AMEs are promising candidates for FIPV treatment, either as monotherapy or in combination therapy. This study provides insights into developing novel therapeutic strategies to combat FIPV infections and offers a foundation for future veterinary antiviral drug development. Full article

Feline coronavirus (FCoV), the causative agent behind feline infectious peritonitis (FIP), is one of the biggest infectious threats to feline health. Despite this threat, the tissue distribution and viral RNA levels in cats infected with feline coronaviruses are poorly understood in the context of natural infection. Here, we used a two-step reverse-transcription quantitative PCR (RT-qPCR) to examine viral RNA levels from different sampling sites in both cats that have been clinically suspected of FIP and their feline housemates. We show that the distribution and amount of FCoV viral RNA does not differ between FCoV-infected cats with FIP and their feline housemates in blood, conjunctiva, or feces. Furthermore, in all FIP and non-FIP cases, viral RNA levels were higher in fecal samples than the blood. Taken together, these results show that amount of viral RNA does not differ between FCoV-infected cats with FIP and their healthy housemates in several sample types. Our results indicate a need for closer examination of FCoV pathogenesis independent of viral dissemination, including an assessment of intrahost evolution of FCoVs and FCoVs’ interactions with the feline immune system. Full article

Background/Objectives: The Tropis^® ID device (PharmaJet^®), a needle-free injection system, is a World Health Organization prequalified, hand-held device, which delivers intradermal injections without the use of needles and has previously been used for the delivery of fractional doses of inactivated polio vaccine (fIPV) in campaign and house-to-house settings. This implementation research study aimed to comparatively evaluate the vaccine coverage, cost, feasibility, and acceptability of using Tropis for fIPV for routine immunizations in two states in Nigeria (Kano and Oyo). Methods: The study included: (i) a cluster randomized trial (22 intervention facilities using Tropis for fIPV and 30 control facilities using the standard of care [SoC—full-dose IPV]) to assess the effectiveness in terms of improving the coverage of two doses of IPV, using a coverage survey involving 3433 children (aged 3–12 months); (ii) a pre- and post-implementation micro-costing evaluation involving the intervention facilities to estimate the costs; and (iii) mixed methods assessments (post-training assessment, provider survey, key informant interviews, and focus group discussions) to assess the feasibility and acceptability of fIPV delivery using Tropis. Results: The intention-to-treat analysis among the 3433 children surveyed did not show any difference between the intervention and control groups, primarily due to low compliance (approximately 50% of target beneficiaries reported Tropis use). The more relevant per protocol analysis, adjusting for lower compliance, showed that among those vaccinated with Tropis, second dose IPV coverage was 11.2% higher than the SoC. The delivery of fIPV using Tropis compared to the SoC resulted in incremental program cost savings, ranging from USD 0.07 to USD 1.00 per dose, administered across the scenarios evaluated. High acceptability was seen amongst caregivers (94%), and 95% of healthcare workers preferred Tropis over the SoC. Conclusions: Tropis is effective, feasible, acceptable, and saves costs when used as part of routine immunization programs. Full article

Background/Objectives: Feline coronavirus (FCoV) belongs to the family Coronaviridae and includes two pathotypes, the less virulent feline enteric coronavirus (FECV), which replicates in the enteric epithelial cells, and feline infectious peritonitis virus (FIPV), which is more virulent, replicates efficiently within monocytes/macrophages with systemic involvement and may cause feline infectious peritonitis (FIP), a progressive and often fatal disease. The diagnosis of FIP is complex and requires different examinations. Among serological tests, the indirect immunofluorescent antibody test (IFAT), considered the gold standard, and the enzyme-linked immunosorbent assay (ELISA) are the most widely used to detect FCoV antibodies. The aim of this work was the development of FCoVCHECK Ab ELISA, a new rapid indirect test for the detection of FCoV antibodies in feline serum/plasma samples. Methods: FCoVCHECK Ab ELISA was developed after a meticulous set-up and cut-off analysis through several methods, including the Youden’s index and ROC curve, to achieve the best test performance. It was validated by testing 110 feline sera (62 positives and 48 negatives) against the reference IFAT and compared with two other rapid ELISA tests, INgezim Corona Felino (Gold Standard Diagnostics) and ImmunoComb Feline Coronavirus (FCoV) [FIP] Antibody Test Kit (Biogal). Conclusions: FCoVCHECK Ab ELISA agreed with IFAT at 96.4% (93.5% sensitivity, 95% confidence interval (CI): 83.5–97.9%; 100% specificity, 95% CI: 90.8–100%), with ImmunoComb FCoV at 93.6% and with INgezim Corona Felino at 82.7%. Intra- and inter-assay accuracy and precision gave coefficients of variation lower than 20%. Compared to IFAT, the new assay correctly identifies positive and negative samples with a good correlation, and, in addition, it is simpler, faster and provides a less subjective reading of the results. Full article

Feline infectious peritonitis virus (FIPV) remains as one of the leading causes of morbidity and mortality in young cats from shelters and catteries worldwide. Since little is known about the molecular characteristics of currently circulating FIPV strains in Long Island, New York, samples from two shelter cats submitted to the Pathology Diagnostic Services of the Long Island University College of Veterinary Medicine, with gross and microscopic lesions consistent with those of FIP were processed for virus isolation, molecular characterization and full-length genome decoding. The younger shelter cat, a 1-year-old male (A15) was found dead without previous signs of illness. Postmortem examination revealed gross and microscopic lesions characterized by vasculitis, necrosis, hemorrhage, and pyogranulomatous inflammation confined to the colon and associated lymph nodes. The second cat, a 7-year-old spayed female (A37) had an identical clinical history and similar but widespread lesions, including fibrinous peritoneal effusion, cecal, colonic, renal, and hepatic involvement. The gross and microscopic diagnosis of FIP in these cats was confirmed by immunohistochemistry (IHC) demonstration of feline coronavirus antigen using mouse anti-FIPV3-70 monoclonal antibody. Virus isolation from saved frozen kidney and colon tissue was performed through several subsequent blind passages in MDCK and Vero cell lines. Confirmation of the FIPV isolation was done through qRT-PCR, IFA, western blot using N protein antibodies, and NGS of the full-length genome sequencing. The full-length genome sequences of the virus isolate from the two cats were decoded using next-generation sequencing (NGS) and deposited in the GenBank as accession numbers PQ192636 and PQ202302. The genome size of these isolates was (29355 and 29321) nucleotides (nt) in length, respectively. While their genome organization was consistent with other FIPV genomes as follows (5’UTR-ORF1ab-S-3abc-M-E-7b-3’UTR-3’), marked differential mutations were observed in the ORF1a/b, S, 3Abc, and 7b protein genes of the two FIPV isolates. One notable deletion of 34 nucleotides was observed in the 7b genes of one of these isolates but was absent in the other. We confirmed the potential recombination events during the evolution of those two FIPV field isolates with the potential parent virus as FECoV-US isolated in 1970 and the potential minor parent as the Canine coronavirus. Our results provide a comprehensive molecular analysis of two novel FIPV isolates causing fatal disease in shelter cats from Long Island. Diagnostic surveillance with molecular characterization and sequencing analysis of circulating FIPV strains within animal shelters may help early detect unique emerging clinical and pathological manifestations of the disease and develop more targeted prophylactic and therapeutic approaches to control it. Full article

Background: Traumatic brain injuries (TBIs) are a common consequence of experiencing intimate partner violence (IPV). IPV-related TBI contributes to adverse health outcomes among women, but it is unknown whether a history of IPV-related TBI negatively impacts safety outcomes following healthcare-based interventions for IPV. Methods: Using data from a larger randomized clinical trial, we explored the impact of IPV-related TBI status on safety-related outcomes in two healthcare-based IPV interventions. At baseline, 35% (n = 21) of the sample screened positive for IPV-related TBI history. We used repeated measures ANOVAs to examine differences in safety outcomes at post-treatment and 1-month follow-up based on treatment condition and IPV-related TBI status. Results: Significant interaction effects were found for safety outcomes, such that women with IPV-related TBI history experienced larger reductions in the frequency of physical IPV and similar reductions in sexual IPV across both treatment conditions compared to women without IPV-TBI (F(2, 102) = 10.88, p < 0.001; F(2, 98) = 3.93, p = 0.036). Conclusions: Findings suggest that brief healthcare-based IPV interventions may result in improvements in safety outcomes for women with a history of IPV-TBI. This highlights the continued need for implementation of promising IPV-focused interventions to promote safety and protect women from experiencing further IPV. Full article

Feline infectious peritonitis (FIP), a serious infectious disease in cats, has become a challenging problem for pet owners and the industry due to the lack of effective vaccinations and medications for prevention and treatment. Currently, most natural compounds have been proven to have good antiviral activity. Hence, it is essential to develop efficacious novel natural compounds that inhibit FIPV infection. Our study aimed to screen compounds with in vitro anti-FIPV effects from nine natural compounds that have been proven to have antiviral activity and preliminarily investigate their mechanisms of action. In this study, the CCK-8 method was used to determine the maximum noncytotoxic concentration (MNTC), 50% cytotoxic concentration (CC₅₀), and 50% effective concentration (EC₅₀) of natural compounds on CRFK cells and the maximum inhibition ratio (MIR) of the compounds inhibit FIPV. The effect of natural compounds on FIPV-induced apoptosis was detected via Annexin V-FITC/PI assay. Network pharmacology (NP), molecular docking (MD), and 4D label-free quantitative (4D-LFQ) proteomic techniques were used in the joint analysis the mechanism of action of the screened natural compounds against FIPV infection. Finally, Western blotting was used to validate the analysis results. Among the nine natural compounds, baicalin had good antiviral effects, with an MIR > 50% and an SI > 3. Baicalin inhibited FIPV-induced apoptosis. NP and MD analyses showed that AKT1 was the best target of baicalin for inhibiting FIPV infection. 4D-LFQ proteomics analysis showed that baicalin might inhibit FIPV infection by modulating the PI3K-AKT pathway and the apoptosis pathway. The WB results showed that baicalin promoted the expression of EGFR, PI3K, and Bcl-2 and inhibited the expression of cleaved caspase 9 and Bax. This study found that baicalin regulated the PI3K-AKT pathway and the apoptosis pathway in vitro and inhibited FIPV-induced apoptosis, thus exerting anti-FIPV effects. Full article

Feline infectious peritonitis (FIP) is a severe and invariably fatal disease affecting both domestic and wild felines with limited effective therapeutic options available. By considering the significant immunomodulatory effects of vitamin E observed in both animal and human models under physiological and pathological conditions, we have provided a full in silico investigation of vitamin E and related compounds and their effect on the crystal structure of feline infectious peritonitis virus 3C-like protease (FIPV-3CL^pro). This work revealed the β-tocotrienol and δ-tocotrienol analogs as inhibitor candidates for this protein, suggesting their potential as possible drug compounds against FIP or their supplementary use with current medicines against this disease. Full article

Background: Effective immunotherapeutic agents for use in cats are needed to aid in the management of intractable viral diseases, including feline infectious peritonitis (FIP) infection. The objectives of this study were to compare two different immune stimulants for antiviral activity in cats: (1) TLR 2/6-activating compound polyprenyl immunostimulant; (PI) and (2) liposome Toll-like receptor 3/9 agonist complexes (LTCs) to determine relative abilities to stimulate the induction of type I (IFN-α, IFN-β) and type II (IFN-γ) interferon immune responses in vitro and to study the effects of treatment on immune responses in healthy cats. Methods: Cytokine and cellular immune responses to PI and LTC were evaluated using peripheral blood mononuclear cells (PBMCs) from healthy cats incubated with LTC and PI at indicated concentrations using reverse transcriptase polymerase chain reaction assays and ELISA assays. The effects of the immune stimulants on inhibiting FIPV replication were assessed using a feline macrophage cell line (fcwf-4). Cytokine and cellular immune responses to PI and LTC were evaluated in blood samples from healthy cats treated with PI and LTC, using reverse transcriptase polymerase chain reaction (RT-PCR) and ELISA assays. Results: In the in vitro studies, both compounds triggered the upregulated expression of IFN-α, IFN-γ, and IL-1β genes in cat PBMC, whereas treatment with LTC induced significantly greater expression of IFN-α and IFN-γ on Day 1 and IL-1b on Day 3. There was significant protection from FIPV-induced cytopathic effects when fcwf-4 cells were treated with conditioned medium from LTC-activated leukocytes. In the healthy cat study (in vivo), both PI and LTC increased the mRNA signal for IFN-α, IFN-γ, and IL-1β above baseline at multiple time points with statistically greater increases in the LTC group on either Day 1 (IFN-α, IFN-γ) or Day 3 (IL-1β). In addition, RANTES increased over time in cats treated with the LTC. Conclusions: Both LTC and PI protocols induced immune-enhancing effects, suggesting a possible clinical use for the management of chronic infectious diseases like FIP. Activating the TLR 3 and 9 pathways (LTC) induced superior broad interferon production in vitro than the activation of the TLR 2 and 6 pathways (PI). Full article

An 8-month-old intact male domestic shorthair cat was referred to the Emergency Service of the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Science of the University of Parma (Italy) from the Parma municipal multi-cat shelter, during the winter season (January 2023), for lethargy, anorexia, hypothermia, and hypoglycemia. At the VTH, upon cardiologic examination, an increase in heart rate, under normal blood pressure conditions, was detected. Signalment, clinical history, basal metabolic panel (BMP), ultrasound investigations, and cytological findings were all consistent with a diagnosis of feline infectious peritonitis (FIP). FIP was confirmed in the effusive abdominal fluid by a molecular genetic test (real-time PCR for feline coronavirus RNA). The molecular genetic investigation also detected an FCoV S gene single-nucleotide mutation: biotype M1058L. At necropsy, an effusive collection was recorded in the abdomen, thoracic cavity, and pericardium sac. White parenchymal nodules, of about 1 mm diameter, were found on the surface and deep in the lungs, liver, kidneys, and heart. Histopathology revealed the typical FIP pyogranulomatous vasculitis and IHC confirmed the presence of the FIP virus (FIPV) antigen. The most relevant histopathological finding was the myocarditis/myocardial necrosis associated with the presence of the S gene-mutated FCoV (M1058L biotype). This is the first case of myocarditis in a cat positive for the FCoV/FIP M1058L biotype. Further studies are necessary to support the mutated FCoV M1058L biotype, as an uncommon, but possible, causative pathogen of myocarditis in FCoV/FIP-positive cats. Studies including several FCoV/FIP M1058L-positive cases could allow us to make a correlation with heart gross pathology, histopathology, and immunolocalization of the FCoV/FIP M1058L biotype in the myocardium. The investigation will potentially allow us to determine the effective tropism of the FCoV/FIP M1058L biotype for myocardiocytes or whether myocardiocyte lesions are evident in the presence of concomitant causes related to the patient, its poor condition, or external environmental distress such as cold season, and whether the aforementioned concomitant events are correlated. Full article

To evaluate the overall prevalence of FIP infection in cats in mainland China and associated risk factors, studies on the prevalence of FIP conducted from 1 January 2008 to 20 December 2023 were retrieved from five databases—CNKI, Wanfang, PubMed, Web of Science, and ScienceDirect—and comprehensively reviewed. The 21 studies selected, with a total of 181,014 samples, underwent a rigorous meta-analysis after quality assessment. The results revealed a 2% prevalence of FIP (95% CI: 1–2%) through the random-effects model, showing considerable heterogeneity (I² = 95.2%). The subsequent subgroup analysis revealed that the age and gender of cats are significant risk factors for FIP infection in mainland China. In order to effectively reduce and control the prevalence of FIP on the Chinese mainland, we suggest improving the immunity of cats, with special attention given to health management in kittens and intact cats, and continuously monitoring FIPV. Full article

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR “serotyped” (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable. Full article

Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to prevent paralytic poliomyelitis continues to be irrefutable, its requirement for strong containment (due to large quantities of live virus used in the manufacturing process), perceived lack of ability to induce intestinal mucosal immunity, high cost and increased complexity to administer compared to oral polio vaccine (OPV), have limited its use in the global efforts to eradicate poliomyelitis. In order to harvest the full potential of IPV, a program of work has been carried out by the Global Polio Eradication Initiative (GPEI) over the past two decades that has focused on: (1) increasing the scientific knowledge base of IPV; (2) translating new insights and evidence into programmatic action; (3) expanding the IPV manufacturing infrastructure for global demand; and (4) continuing to pursue an ambitious research program to develop more immunogenic and safer-to-produce vaccines. While the knowledge base of IPV continues to expand, further research and product development are necessary to ensure that the program priorities are met (e.g., non-infectious production through virus-like particles, non-transmissible vaccine inducing humoral and intestinal mucosal immunity and new methods for house-to-house administration through micro-needle patches and jet injectors), the discussions have largely moved from whether to how to use this vaccine most effectively. In this review, we summarize recent developments on expanding the science base of IPV and provide insight into policy development and the expansion of IPV manufacturing and production, and finally we provide an update on the current priorities. Full article