BackgroundMyocarditis and myocardial injury associated with feline infectious peritonitis (FIP) recently are being recognized.Hypothesis/ObjectivesProspectively document the frequency of cardiac changes in cats with FIP using echocardiography and cardiac troponin I (cTnI) concentrations.AnimalsTwenty cats with naturally occurring FIP without previous history of heart disease.MethodsCats diagnosed with FIP were tested for common concurrent infections associated with myocarditis by testing serum for feline immunodeficiency virus (FIV) antibodies, feline leukemia virus antigen (FeLV), Dirofilaria immitis antigen, Bartonella spp. immunoglobulin G (IgG), and Toxoplasma gondii IgG and immunoglobulin M (IgM) as well as by testing blood for nucleic acids of Bartonella spp. and coronavirus (SARS-COV-2). Each cat also was tested for serum cTn1 concentration and underwent an echocardiographic examination. After 12 weeks of treatment with antiviral drugs, serum cTnI concentrations were reassessed.ResultsAll echocardiographic measurements were normalized to patient body weight. The left ventricular posterior wall from right parasternal long axis and short axis was thickened in 55% (11/20) and 25% (5/20) of cats, respectively. Pleural effusion was present in 40% (8/20) of cats and pericardial effusion in 25% (5/20) of cats, but a cardiac cause was not identified for these effusions. Median cTnI at initial evaluation was 0.37 ng/ml (interquartile range [IQR], 0.20-0.83; upper reference interval, 0.20 ng/ml). Repeat cTnI was performed after 12 weeks of antiviral treatment in 6 cats that initially had increased cTnI (median initial cTnI, 0.75 ng/mL) and, in all 6 cats, cTnI normalized to < 0.20 ng/mL.Conclusions and clinical importanceCats with FIP can present with increases in cTnI and ventricular wall thickening, findings suggestive of myocarditis or myocardial injury.

ObjectivesFeline leukaemia virus (FeLV) infection-particularly the progressive course-continues to cause substantial morbidity and reduced survival in cats. Therapeutic options with proven antiviral effectiveness remain limited. This study aimed to evaluate the clinical and virological effects of the integrase inhibitor raltegravir in naturally infected, FeLV-progressive cats with FeLV-related conditions, clinical outcome, viraemia, proviral burden and survival.MethodsFourteen client-owned cats with confirmed progressive FeLV infection and at least one FeLV-related condition was enrolled. Raltegravir was administered for 90 days, followed by a 90-day treatment-free observation period. Clinical evaluation and quantification of viral RNA and proviral DNA loads were performed at treatment initiation (t0), day 45 (t45), day 90 (t90) and day 180 (t180). Cats continued to receive standard-of-care as clinically indicated. Survival data were recorded until study closure.ResultsAfter 45 days of treatment, plasma viral RNA load showed a non-significant mean reduction of 1.34 log₁₀ (P = 0.204). At day 90, mean viral load continued to decrease, with reductions of 1.10 log₁₀ at 40 mg (P = 0.208) and 1.39 log₁₀ at 80 mg (P = 0.195), none of which reached statistical significance. Raltegravir did not exert a consistent effect on proviral DNA load. Most FeLV-related conditions remained clinically stable or improved during the 180-day monitoring period. Leukaemia and lymphoma were the main causes of death. Median survival time was 48 months from FeLV diagnosis and 10.8 months from treatment initiation.Conclusions and relevanceTo the authors' knowledge, this is the first prospective longitudinal study in naturally infected, FeLV-progressive cats with FeLV-related conditions assessing the effects of raltegravir on viraemia, proviral load and clinical outcomes. These real-world data suggest that raltegravir may be associated with numerical reductions in viraemia and clinical stabilisation in some cats. A definitive virological or survival benefit, however, could not be demonstrated. Longer-term, controlled studies-potentially within multimodal antiviral strategies-are warranted to further define its therapeutic role.

Emerging viral diseases-particularly zoonotic pathogens-affect the health and conservation of endangered felids, including Panthera tigris altaica (Amur tiger) and Panthera pardus (leopard). To address this challenge, we employed a viromics approach to investigate the diversity of the fecal virome in wild felids and assess its zoonotic potential. Using in-depth metagenomic sequencing and analysis of fecal samples from captive wild felids housed in a wildlife institution, this study characterized the enteric virome and evaluated associated risks. A total of 18 viral families and 48 viral genera were identified. The DNA virus community exhibited stability in abundance and composition, dominated by the phyla Heunggongvirae and Bamfordvirae. Within Heunggongvirae, the class Caudoviricetes was the core component, with its abundance aligning with the intestinal bacterial community, suggesting a potential role of these bacteriophages in regulating microbial ecology. Additionally, sequences of the family Poxviridae, homologous to Variola virus (VARV), were detected. In contrast, the RNA virus community displayed higher diversity and variability, with the order Ortervirales as the predominant group. Sequences highly homologous to feline leukemia virus (FeLV) were repeatedly identified, suggesting potential latent infections. The detection of sequences related to rare environmental viruses, such as Casadabanvirus, highlights the potential risk of cross-species virus transmission under captive conditions. Stability analysis revealed that dominant DNA virus groups exhibited low abundance variability across samples. In contrast, unclassified RNA viral taxa showed higher abundance variability. KEGG functional annotation mapped DNA viral contigs primarily to microbial metabolic modules. Conversely, RNA assemblies extensively mapped to eukaryotic pathways (e.g., arachidonic acid and energy metabolism); due to the total nucleic acid extraction methodology, these mappings primarily reflect co-extracted host transcriptomic background rather than viral-encoded functions, providing an indirect snapshot of the concurrent enteric microenvironment. These baseline data delineate the virome structure in captive environments and provide practical targets for zoological biosecurity and proactive veterinary surveillance.

Domestic cat hepatitis B virus (DCHBV) is a member of the Hepadnaviridae family and has been associated with hepatocellular carcinoma (HCC) in cats. This study aimed to determine the prevalence of DCHBV and associations with feline immunodeficiency virus (FIV), feline leukaemia virus (FeLV) and feline coronavirus (FCoV) infections in cats in Serbia, and to characterise the detected DCHBV genomes. Whole blood, serum and liver samples from 308 animals were screened by real-time (RT-)PCR for DCHBV, FIV, FeLV, and FCoV. The prevalence of DCHBV was 2.60%, with no significant associations observed between DCHBV infection and age, sex, or coinfection status. Three whole genome sequences were obtained, and phylogenetic analysis demonstrated that the Serbian strains belong to genotype A. Molecular analysis revealed three unique nonsynonymous substitutions in the S ORF. Within the C ORF, a 28-amino acid N-terminal precore region with conserved cysteine residues critical for protein maturation was identified, along with the C-terminal arginine-rich domain. A putative core promoter region was detected, containing two motifs analogous to the pgRNA and pcRNA initiator elements described in hepatitis B virus (HBV). DCHBV sequences contained two 11-bp direct repeats with DR2 located in X ORF and DR1 positioned in the C ORF. This study represents the first report of DCHBV in Serbia, providing new insights into its epidemiology and genomic features. The findings expand current knowledge of its molecular diversity and underscore the importance of genomic characterisation for understanding its role in liver disease development.

Allogeneic mesenchymal stromal cell therapy for nonregenerative anemia in a FeLV-infected cat: a case report.

Feline leukemia virus (Gammaretrovirus felleu) causes variable pathologies, partially modulated by its endogenous form (enFeLV). Although enFeLV is found in genomes of all species of the Felis genus, the limitations of transposable element sequencing have hindered a comprehensive characterization. In this study, we examined 17 felid genomes for enFeLV copies, confirming that enFeLV is restricted to the Felis genus. From the long-read genomes of Felis catus, Felis nigripes, and Felis chaus, we identified 73 solo LTRs, 64 copies with genic segments, and 4 atypical copies. These were annotated and characterized using recombination assessment, phylogenetic analysis, insertion dating, and Fisher's exact tests. All enFeLV copies shared a single origin, with insertions occurring within the last 3.5 million years, except for predicted recombinants. Copy distribution, dating, and the phylogenetic position of F. chaus copies reinforce the hypothesis of a recent introgression of enFeLV into this species. Furthermore, 41 copies exhibit identical LTR pairs and 14 retain intact open reading frames spanning the viral genome. Uneven evolutionary pressures across the enFeLV genome were evidenced by discrepancies between tree topologies of individual genes and the preferential loss of pol. We conclude that enFeLV has undergone a complex post-endogenization evolutionary history and urge additional studies of other endogenous retroviruses.

FLVCR2: structure, substrate transport, and emerging roles in human disease.

Lymphoma is the most common neoplastic disease in cats; however, lomustine has been insufficiently evaluated as a first-line chemotherapeutic agent. This study assessed treatment response, survival, and progression-free interval (PFI) in cats with intermediate-to-large cell lymphoma treated with lomustine and prednisolone as first-line therapy. Twenty-eight cats with cytologically or histopathologically confirmed lymphoma received lomustine (10 mg/cat every 3 weeks) and prednisolone until disease progression or unacceptable toxicity. All cats were feline leukemia virus- and feline immunodeficiency virus-negative, with a mean age of 9.93 years; alimentary lymphoma was most common (75%). Treatment responses included complete response (CR, 5/28), partial response (5/28), stable disease (11/28), and progressive disease (7/28). The median PFI for all cats was 51 days, and the median survival time was not reached during the study period. No significant associations were identified between PFI or survival and age, sex, packed cell volume, drug dosage, tumor size, or tumor location. Cats achieving CR showed significantly prolonged PFI compared with cats with other responses (median, 561 vs. 42 days; p = 0.0004), and overall survival was also significantly longer (p = 0.0009). These findings may serve as a clinically meaningful guide for the use of lomustine and prednisolone in the treatment of feline lymphoma.

There is limited information about treatment success and outcomes in retrovirus-positive cats diagnosed with feline infectious peritonitis (FIP). A survey was distributed to caretakers of cats with feline leukemia virus (FeLV) and/or feline immunodeficiency virus (FIV) that were treated with GS-441524 for presumptive effusive FIP based on survey responses. Cats with FIV developed FIP at an older age and longer after retrovirus infection than cats with FeLV. The average starting dosage (7 mg/kg/d) was increased in 65% of cats, and treatment was extended in 35%. Three cats relapsed (18%). There was a 94% (16/17) twelve-week survival rate and 82% (14/17) one-year survival rate. Seven cats were alive at follow-up, a median of 1306 days (range 983-2069) after FIP diagnosis, but many cats succumbed to neoplasia. Treatment success for retrovirus-positive cats with presumptive FIP was similar to previously reported outcomes for FIP alone. This could support current evidence of successful antiviral therapy for similar populations, if noncurrent, unstandardized protocols and unlicensed product use are considered. Additional studies are needed to determine ideal protocols for rapid resolution of FIP, good long-term survival, and limited relapse in retrovirus-positive cats, and the impact of the FeLV proviral load.

Ribosome profiling has revealed thousands of noncanonical translation events across mammalian genomes, yet functional characterization has overwhelmingly focused on proliferative fitness in cancer cell lines. Here, we present a comprehensive survey of noncanonical translation in the mouse immune system and its functional consequences in macrophages. By performing a unified Ribo-seq meta-analysis across 20 public mouse leukocyte datasets - spanning macrophages, dendritic cells, neutrophils, B cells, and T cells - we define a compendium of 22,276 noncanonical coding sequences (CDSs), including upstream ORFs (uORFs), downstream ORFs, and ORFs on noncoding RNAs and pseudogenes (ncORFs). Proteogenomic integration with reanalyzed mass spectrometry data prioritizes a high-confidence subset with detectable protein products, including pseudogene-encoded and lncRNA-encoded zinc finger proteins. To move beyond cataloging, we carried out two orthogonal CRISPR screens in immortalized bone marrow-derived macrophages: a fitness screen identifying noncanonical CDSs required for macrophage viability, and a TLR1/TLR2-NFκB reporter screen uncovering CDSs that modulate innate immune signaling. These screens nominate uORFs, several conserved between mouse and human, that exert phenotypic effects on par with their cognate coding sequences. We unexpectedly discovered a family of endogenous retroviral envelope-derived proteins translated in adult myeloid cells. Among these, SYNIR is a full-length syncytin-like membrane glycoprotein that positively regulates NFκB-responsive transcription, while SEMR is a secreted protein with structural homology to the feline leukemia virus accessory protein FeLIX that drives broad transcriptional remodeling of macrophage gene programs upon knockout. Updated single-cell RNA-seq annotations and an interactive UCSC Genome Browser session integrating Ribo-seq, proteomics, and CRISPR screen data are provided as community resources. Together, these findings expand the functional landscape of noncanonical translation in immunity and establish endogenous retroviral proteins as previously unrecognized regulators of macrophage biology.

Genetic pain loss disorders represent a heterogeneous group of rare diseases mainly characterized by defective nociception. Understanding the underlying molecular mechanism is fundamental to improve the treatment of patients affected by these rare disorders. Feline Leukemia Virus Subgroup C Receptor 1 (FLVCR1) is one of the genes previously associated with sensory neuropathy that requires further investigation. Here, we report on two additional patients with novel disease-causing variants in FLVCR1 and introduce a zebrafish model of the disease. The analyses of patient-derived fibroblasts show that distinct FLVCR1 variants compromised all the known functions associated with FLVCR1, thus affecting choline levels, heme biosynthesis and mitochondrial Ca2+ handling. Furthermore, we provide evidence that the alteration of these processes impairs the TCA cycle and OXPHOS, and induces lipid peroxidation. Our data points to the alterations of energetic metabolism as a potential driving pathomechanism in FLVCR1-associated sensory neuropathy.

The Feline Leukaemia Virus Subgroup C Receptor 1 (FLVCR1) has been recognized as a heme exporter essential for erythropoiesis, and emerging research identifies its novel function as a choline transporter. Mutations in FLVCR1 have been associated with the pathogenesis of retinitis pigmentosa (RP); however, the roles of FLVCR1 in retina remain unexplored. This study aims to elucidate the connection between FLVCR1 and RP and investigate potential therapeutic interventions. Utilizing CRISPR/Cas9 technology, we established retina-specific Flvcr1 knockout (SKO) and rod-specific Flvcr1 knockout (RKO) mouse models to investigate the invivo functions of FLVCR1 in the retina. We performed optical coherence tomography (OCT) to assess the retinal thickness, electroretinography (ERG) to test the retinal function and histopathological sections and staining to analyse the pathological changes. Additionally, we administered choline supplementation treatment (CST)to evaluate its potential efficacy in alleviating symptoms of retinal degeneration. Genotyping and immunoblotting analyses confirmed the successful establishment of the SKO and RKO mouse models. Retinal degeneration in SKO mice manifested at postnatal day 14, while its onset in RKO mice occurred at P25, including diminished scotopic electroretinogram (ERG) responses, progressive degeneration of photoreceptor cells, infiltration of microglia into the outer nuclear layer (ONL) and disruption of mitochondrial homeostasis. Notably, we found that choline supplementation in RKO mice alleviated the associated phenotypes. We developed two innovative mouse models and revealed that FLVCR1 is critical for maintaining mitochondrial homeostasis and supporting photoreceptor survival. Choline supplementation serves as a therapeutic intervention for RP caused by FLVCR1 mutations.

Case series summaryFatal feline infectious peritonitis (FIP), caused by feline coronavirus (FCoV), can now be cured with GS-441524. Only a few unexpected clinical and laboratory observations have been reported with treatment, including lymphocytosis, eosinophilia and long-term persistence of abdominal lymphadenomegaly. Yet immune overstimulation associated with FIP might have negative long-term consequences. This report describes four cases of large-cell lymphoma (LCL) arising within 2 years of FIP diagnosis and successful treatment with legally sourced oral GS-441524 (15 mg/kg q24h), representing an incidence of 2.0% (n = 4/202) in a large treatment cohort. At LCL diagnosis, two cats were aged under 2 years, one was aged 8 years and one was aged 13 years. All cats showed weight loss, three had hyporexia and two had chronic vomiting; all tested negative for feline leukaemia virus and feline immunodeficiency virus. LCL was diagnosed by histology (n = 3) or cytology (n = 1) at 81, 365 (n = 2) and 595 days after FIP diagnosis/treatment start. The cats died a median of 15.5 days after LCL diagnosis. Neither a high FCoV viral load nor FCoV antigen, as determined by semi-quantitative RT-PCR and immunohistochemistry, respectively, was detected in any of the available samples. PCR for antigen receptor rearrangements revealed a monoclonal B-cell population in two cats, supporting a diagnosis of large B-cell lymphoma.Relevance and novel informationThe incidence of LCL reported here among cats in remission from FIP after legally sourced oral GS-441524 treatment is remarkably high compared with the general feline population. LCL should be considered a potential 'long-FIP syndrome' and/or a long-term complication after GS-441524 treatment. The pathogenesis of LCL in this context requires further clarification.

In a 2019 Pan-European Study, Portugal exhibited the highest prevalence of Feline Leukemia Virus (FeLV) infection (8.8%). Following the coronavirus disease 2019 (COVID-19) pandemic, it is crucial to evaluate how the prevalence of FeLV has evolved. FeLV infection is associated with the highest morbidity rates, primarily due to the increased incidence of diseases that compromise the health of cat populations, which varies according to the lifestyle and background of the cats studied. This study aimed (1) to estimate the prevalence and temporal trends of FeLV and FIV infections among cats presented to a university veterinary hospital in the Lisbon metropolitan area, and (2) to evaluate the clinical associations between FeLV infection, health status, and FeLV-related conditions in cats. Conducted over 4.5 years, from January 2019 to July 2023, this cross-sectional study took place at a teaching hospital and involved 1,124 cats that were tested serologically and/or by qPCR and RT-qPCR for FeLV. Information was gathered on the intrinsic and extrinsic characteristics of the cats, their health status, and any related diseases. The overall prevalence of FeLV was found to be 11.3% (95% CI: 9.5%−13.3%), with 1.8% (95% CI: 1.1%−2.7%) of cats co-infected with FIV, and it peaked in 2020 at 14.1% (95% CI: 7.5%−23.4%), with 2.4% (95% CI: 0.03%−8.2%) co-infected with FIV. Over the 4.5-year period, an increasing number of cats were tested, and more quantification of proviral and viral loads was performed. This indicated a more progressive course in 47.0% (31/66), of sick FeLV-infected cats, who exhibited a higher incidence of FeLV-related diseases. Although there was no significant difference in the average age between positive and negative cats, FeLV-positive cats demonstrated a higher rate of sickness (74.8%, n = 95). To the best of the authors’ knowledge, this study represents the largest cross-sectional investigation of FeLV infection prevalence and its health implications conducted in Portugal. Overall, the available data suggest a possible increase in FeLV prevalence in Portugal, concurrent with a declining vaccination rate from 14.2% to 5.0%. The results also highlight notable differences in clinical status between progressive and regressive disease courses, reinforcing the necessity of staging the course of infection at diagnosis to ensure an informed medical approach and realistic prognosis. Efforts should focus on improving vaccination and screening activities, promoting neutering of indoor and outdoor cats, and isolating infected cats.

Intranasal immunization of recombinant vaccinia virus bearing FeLV SU elicits systemic and mucosal immunity.

Injections have been linked to feline sarcomas (feline injection-site sarcoma; FISS) and cutaneous lymphomas (cutaneous lymphoma at injection site; CLIS). Both tumors often exhibit lymphoplasmacytic inflammation ascribed to injected immunogenic material. CLIS is hypothesized to emerge from transformation and clonal expansion of lymphoid cells following persistent immune stimulation with feline leukemia virus (FeLV) reactivation and transformation. To further study whether the lymphocytic infiltrates associated with FISS can represent a suitable niche for the development of CLIS, 34 cases of FISS were examined. Lymphoid cell phenotypes were assessed using CD3 and CD79 immunohistochemistry. For cases with prominent inflammation, FeLV p27 and gp70 immunohistochemistry and PCR for antigen receptor rearrangements were performed. Male domestic shorthair cats predominated. The mean age was 12.2 years (range: 5-17 years). FISS developed in thoracic (8/34, 24%), flank (7/34, 21%), and interscapular (5/34, 15%) regions. Similar proportions of B and T lymphocytes were found in 11/34 (32%) cases; T-cells predominated in 12/34 (35%) cases, and B-cells predominated in 11/34 (32%). At least one FeLV antigen was expressed in lymphoid infiltrates in 10/18 cases (55%), and in neoplastic fibroblasts in 8/18 cases (44%), while both FeLV proteins were expressed in neoplastic cells in 3/18 cases (17%). One cat had clonal T-cell receptor-gamma and was diagnosed with concurrent FISS and CLIS. This case lacked FeLV expression. FeLV amplification from formalin-fixed paraffin-embedded material was unsuccessful. The expression of FeLV p27 and/or gp70 in neoplastic spindle cells and lymphoid infiltrates raises the possibility of FeLV involvement in the tumorigenesis of FISS and CLISs.

This study aimed to determine the true prevalence of feline leukemia virus (FeLV) infections in apparently healthy and sick shelter cats in Mississippi and estimate the predictive value of a lateral flow test results at the estimated true prevalences to guide testing recommendations. Blood samples (n = 383) were collected from a convenience sample of healthy and sick cats from February 2021 to July 2023. Blood serum samples from both apparently healthy and sick cats were tested for FeLV using lateral flow and insulated isothermal PCR (iiPCR) testing methods. Bayesian latent class modeling was used to estimate test performance and predictive value in both populations. The estimated true prevalence of FeLV in apparently healthy cats was 0.8% (95% CI 0.1%, 2.2%) and 5.3% (95% CI 1.3%, 11.5%) in sick cats. At these prevalences, the estimated positive predictive value of FeLV in healthy cats was 40.1% (95% CI 4.1%, 85.2%) and 99.0% (95% CI 99.4%, 100%) in sick cats. Negative predictive value of FeLV in healthy cats was 79.8% (95% CI 45.2%, 96.8%) and 99.2% (95% CI 97.1%, 100%) in sick cats. The predictive value of a positive test is low for healthy cats. Serial testing may not meaningfully improve the positive predictive value. Positive and negative predictive values were better for sick cats and may have diagnostic utility. Current testing methods may not be adequate for controlling the disease in population.

Feline hematopoietic neoplasms associated with retroviruses pose a diagnostic and therapeutic challenge, especially when they present with atypical morphological features that do not fit conventional classifications. This work describes the first reported case worldwide of atypical chronic myelomonocytic leukemia of eosinophilic lineage in a cat positive for feline leukemia virus, diagnosed through detailed cytomorphological analysis and the use of enzymatic cytochemical stains. The rarity of this case underscores the importance of documenting and studying uncommon presentations, with the goal of expanding clinical knowledge and strengthening diagnostic tools in feline veterinary medicine.

Retroperitoneal T-cell lymphoma with cystitis and megacolon in a young feline leukaemia virus-positive cat.

Lymphoma is a common neoplasm in cats, in which alimentary lymphoma is a common subtype, and it is usually diagnosed in elderly, feline leukemia virus (FeLV)-negative cats. This study aimed to describe the pathological features of lymphoma with involvement of the alimentary tract in FeLV-antigen-positive cats. In a 12-year retrospective study, 32 necropsied and FeLV-infected cats with lymphoma affecting the alimentary tract were identified. Twenty-one cases were multicentric lymphomas with secondary involvement of the alimentary tract, and the remaining 11 cats were considered to have primary alimentary lymphoma. The small intestine was the most common anatomic location (23/32; 72%), followed by the large intestine (19/32; 59%) and stomach (18/32; 56%). In 22/32 cases (69%), multiple organs within the alimentary tract were concomitantly affected. Thickening of the intestinal and gastric walls was the most common gross lesion (23/32; 72%), while mural nodules were observed in 16/32 cats (50%). The mesenteric lymph nodes were frequently affected (22/32; 69%). Most lymphomas were composed of large (17/32; 53%) and intermediate cells (14/32; 44%). B-cell lymphomas were more frequent (24/32; 75%), and diffuse large B-cell lymphoma was the most common diagnosis (15/32; 47%). In 31/32 (97%) cases, FeLV gp70 antigen was detected in neoplastic lymphocytes by immunohistochemistry. Lymphomas affecting the alimentary tract may be observed in FeLV-infected, young adult cats, in which large to intermediate cell and B-cell lymphomas are more frequently observed, and small cell T-cell intestinal lymphoma is unlikely to be diagnosed.