scholarly journals Intrahost Diversity of Feline Coronavirus: A Consensus between the Circulating Virulent/Avirulent Strains and the Internal Mutation Hypotheses?

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Aline S. Hora ◽  
Karen M. Asano ◽  
Juliana M. Guerra ◽  
Ramon G. Mesquita ◽  
Paulo Maiorka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Molecular Diversity ◽  
Gene Tree ◽  
Gene Mutations ◽  
Geographic Pattern ◽  
M Gene ◽  
Feline Infectious Peritonitis ◽  
Faecal Samples ◽  
Feline Coronavirus

To evaluate the most controversial issue concerning current feline coronavirus (FCoV) virology, the coexisting hypotheses of the intrahost and interhost origins of feline infectious peritonitis virus (FIPV) in regard to the pathogenesis of feline infectious peritonitis (FIP), this study aimed to assess the molecular diversity of the membrane gene FCoVs in 190 samples from 10 cats with signs of FIP and in 5 faecal samples from cats without signs of FIP. All samples from the non-FIP cats and 25.26% of the samples from the FIP cats were positive for the FCoV membrane (M) gene. Mutations in this gene consisted of SNP changes randomly scattered among the sequences; few mutations resulted in amino acid changes. No geographic pattern was observed. Of the cats without FIP that harboured FECoV, the amino acid sequence identities for the M gene were 100% among cats (Cats 1–3) from the same cattery, and the overall sequence identity for the M gene was ≥91%. In one cat, two different lineages of FCoV, one enteric and one systemic, were found that segregated apart in the M gene tree. In conclusion, the in vivo mutation transition hypothesis and the circulating high virulent-low virulent FCoV hypothesis have been found to be plausible according to the results obtained from sequencing the M gene.

scholarly journals Characterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitor

2019 ◽  
Vol 237 ◽  
pp. 108398 ◽  
Author(s):  
Krishani Dinali Perera ◽  
Athri D. Rathnayake ◽  
Hongwei Liu ◽  
Niels C. Pedersen ◽  
William C. Groutas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protease Inhibitor ◽  
Amino Acid Substitutions ◽  
Feline Infectious Peritonitis ◽  
Feline Coronavirus

scholarly journals Detection of feline coronavirus spike gene mutations as a tool to diagnose feline infectious peritonitis

2016 ◽  
Vol 19 (4) ◽  
pp. 321-335 ◽  
Author(s):  
Sandra Felten ◽  
Karola Weider ◽  
Stephanie Doenges ◽  
Stefanie Gruendl ◽  
Kaspar Matiasek ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Control Group ◽  
Nested Polymerase Chain Reaction ◽  
Feline Infectious Peritonitis ◽  
Spike Gene ◽  
S Gene ◽  
Pcr Products ◽  
Study Population ◽  
Polymerase Chain ◽  
Feline Coronavirus

Objectives Feline infectious peritonitis (FIP) is an important cause of death in the cat population worldwide. The ante-mortem diagnosis of FIP in clinical cases is still challenging. In cats without effusion, a definitive diagnosis can only be achieved post mortem or with invasive methods. The aim of this study was to evaluate the use of a combined reverse transcriptase nested polymerase chain reaction (RT-nPCR) and sequencing approach in the diagnosis of FIP, detecting mutations at two different nucleotide positions within the spike (S) gene. Methods The study population consisted of 64 cats with confirmed FIP and 63 cats in which FIP was initially suspected due to similar clinical or laboratory signs, but that were definitively diagnosed with another disease. Serum/plasma and/or effusion samples of these cats were examined for feline coronavirus (FCoV) RNA by RT-nPCR and, if positive, PCR products were sequenced for nucleotide transitions within the S gene. Results Specificity of RT-nPCR was 100% in all materials (95% confidence interval [CI] in serum/plasma 83.9–100.0; 95% CI in effusion 93.0–100.0). The specificity of the sequencing step could not be determined as none of the cats of the control group tested positive for FCoV RNA. Sensitivity of the ‘combined RT-nPCR and sequencing approach’ was 6.5% (95% CI 0.8–21.4) in serum/plasma and 65.3% (95% CI 50.4–78.3) in effusion. Conclusions and relevance A positive result is highly indicative of the presence of FIP, but as none of the control cats tested positive by RT-nPCR, it was not possible to confirm that the FCoV mutant described can only be found in cats with FIP. Further studies are necessary to evaluate the usefulness of the sequencing step including FCoV-RNA-positive cats with and without FIP. A negative result cannot be used to exclude the disease, especially when only serum/plasma samples are available.

scholarly journals Feline Coronavirus Antivirals: A Review

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1150
Author(s):  
Manon Delaplace ◽  
Hélène Huet ◽  
Adèle Gambino ◽  
Sophie Le Poder
Keyword(s):  
Research Area ◽  
Viral Escape ◽  
Viral Pathogens ◽  
Feline Infectious Peritonitis ◽  
Escape Mutants ◽  
Asymptomatic Infections ◽  
Therapeutic Compounds ◽  
Feline Coronavirus

Feline coronaviruses (FCoV) are common viral pathogens of cats. They usually induce asymptomatic infections but some FCoV strains, named Feline Infectious Peritonitis Viruses (FIPV) lead to a systematic fatal disease, the feline infectious peritonitis (FIP). While no treatments are approved as of yet, numerous studies have been explored with the hope to develop therapeutic compounds. In recent years, two novel molecules (GS-441524 and GC376) have raised hopes given the encouraging results, but some concerns about the use of these molecules persist, such as the fear of the emergence of viral escape mutants or the difficult tissue distribution of these antivirals in certain affected organs. This review will summarize current findings and leads in the development of antiviral therapy against FCoV both in vitro and in vivo, with the description of their mechanisms of action when known. It highlights the molecules, which could have a broader effect on different coronaviruses. In the context of the SARS-CoV-2 pandemic, the development of antivirals is an urgent need and FIP could be a valuable model to help this research area.

scholarly journals Detection of feline coronavirus RNA, spike gene mutations, and feline coronavirus antigen in macrophages in aqueous humor of cats in the diagnosis of feline infectious peritonitis

2020 ◽  
Vol 32 (4) ◽  
pp. 527-534
Author(s):  
Laura Sangl ◽  
Sandra Felten ◽  
Kaspar Matiasek ◽  
Stefanie Dörfelt ◽  
Michele Bergmann ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Point Mutations ◽  
Gene Mutations ◽  
Control Group ◽  
Complex Method ◽  
Predictive Values ◽  
Feline Infectious Peritonitis ◽  
Spike Gene ◽  
Sensitivity Specificity ◽  
Feline Coronavirus

Uveitis is common in cats, and is often a feature of feline infectious peritonitis (FIP). We evaluated 3 tools for detection of feline coronavirus (FCoV) in aqueous humor: 1) a 7b gene reverse-transcription real-time PCR ( 7b-RT-rtPCR) assay to detect FCoV RNA, 2) a spike gene mutation RT-rtPCR ( S-RT-rtPCR) assay to detect 2 point mutations in the spike gene of FCoV in cats positive by 7b-RT-rtPCR, and 3) immunocytochemistry (ICC) for detection of FCoV antigen in aqueous humor macrophages. We studied 58 cats, including 31 cats with FIP and 27 control cats. FIP was excluded by postmortem examination and negative immunohistochemistry (IHC). Aqueous humor samples obtained postmortem were assessed using 7b-RT-rtPCR in all cats, and positive samples were evaluated with S-RT-rtPCR. ICC evaluation of aqueous humor samples from 36 of the 58 cats was done using an avidin–biotin complex method and monoclonal anti-FCoV IgG 2A. Sensitivity, specificity, and negative and positive predictive values were calculated including 95% CIs. 7b-RT-rtPCR had a specificity of 100.0% (95% CI: 87.2–100.0) and sensitivity of 35.5% (95% CI: 19.2–54.6). Specificity of S-RT-rtPCR could not be determined because there were no FCoV 7b-RT-rtPCR–positive samples in the control group. Sensitivity of S-RT-rtPCR was 12.9% (95% CI 3.6–29.8). Sensitivity and specificity of ICC were 62.5% (95% CI: 40.6–81.2) and 80.0% (95% CI: 44.4–97.5), respectively. The combination of 7b-RT-rtPCR and IHC could be useful in diagnosing FIP; S-RT-rtPCR did not add value; and ICC of aqueous humor samples cannot be recommended for the diagnosis of FIP.

scholarly journals Diagnostic Value of Detecting Feline Coronavirus RNA and Spike Gene Mutations in Cerebrospinal Fluid to Confirm Feline Infectious Peritonitis

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Sandra Felten ◽  
Kaspar Matiasek ◽  
Christian M. Leutenegger ◽  
Laura Sangl ◽  
Stephanie Herre ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Confidence Interval ◽  
Clinical Signs ◽  
Gene Mutations ◽  
Diagnostic Value ◽  
Feline Infectious Peritonitis ◽  
Future Studies ◽  
Spike Gene ◽  
Neurological Signs ◽  
Feline Coronavirus

Background: Cats with neurologic feline infectious peritonitis (FIP) are difficult to diagnose. Aim of this study was to evaluate the diagnostic value of detecting feline coronavirus (FCoV) RNA and spike (S) gene mutations in cerebrospinal fluid (CSF). Methods: The study included 30 cats with confirmed FIP (six with neurological signs) and 29 control cats (eleven with neurological signs) with other diseases resulting in similar clinical signs. CSF was tested for FCoV RNA by 7b-RT-qPCR in all cats. In RT-qPCR-positive cases, S-RT-qPCR was additionally performed to identify spike gene mutations. Results: Nine cats with FIP (9/30, 30%), but none of the control cats were positive for FCoV RNA in CSF. Sensitivity of 7b-RT-qPCR in CSF was higher for cats with neurological FIP (83.3%; 95% confidence interval (95% CI) 41.8–98.9) than for cats with non-neurological FIP (16.7%; 95% CI 6.1–36.5). Spike gene mutations were rarely detected. Conclusions: FCoV RNA was frequently present in CSF of cats with neurological FIP, but only rarely in cats with non-neurological FIP. Screening for spike gene mutations did not enhance specificity in this patient group. Larger populations of cats with neurological FIP should be explored in future studies.

scholarly journals Pharmacokinetic Profile of Oral Administration of Mefloquine to Clinically Normal Cats: A Preliminary In-Vivo Study of a Potential Treatment for Feline Infectious Peritonitis (FIP)

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1000
Author(s):  
Jane Yu ◽  
Benjamin Kimble ◽  
Jacqueline M. Norris ◽  
Merran Govendir
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Feline Calicivirus ◽  
Potential Treatment ◽  
Feline Infectious Peritonitis ◽  
Feline Coronavirus

The pharmacokinetic profile of mefloquine was investigated as a preliminary study towards a potential treatment for feline coronavirus infections (such as feline infectious peritonitis) or feline calicivirus infections. Mefloquine was administered at 62.5 mg orally to seven clinically healthy cats twice weekly for four doses and mefloquine plasma concentrations over 336 h were measured using high pressure liquid chromatography (HPLC). The peak plasma concentration (Cmax) after a single oral dose of mefloquine was 2.71 ug/mL and time to reach Cmax (Tmax) was 15 h. The elimination half-life was 224 h. The plasma concentration reached a higher level at 4.06 ug/mL when mefloquine was administered with food. Adverse effects of dosing included vomiting following administration without food in some cats. Mild increases in serum symmetric dimethylarginine (SDMA), but not creatinine, concentrations were observed. Mefloquine may provide a safe effective treatment for feline coronavirus and feline calicivirus infections in cats.

scholarly journals Development of Biomarkers for Inhibition of SLC6A19 (B0AT1)—A Potential Target to Treat Metabolic Disorders

2018 ◽  
Vol 19 (11) ◽  
pp. 3597 ◽  
Author(s):  
Kiran Javed ◽  
Qi Cheng ◽  
Adam Carroll ◽  
Thy Truong ◽  
Stefan Bröer
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Metabolic Diseases ◽  
Protein Restriction ◽  
Gas Chromatography Mass Spectrometry ◽  
Roc Curve Analysis ◽  
Neutral Amino Acids ◽  
Faecal Samples

Recent studies have established that dietary protein restriction improves metabolic health and glucose homeostasis. SLC6A19 (B0AT1) is the major neutral amino acid transporter in the intestine and carries out the bulk of amino acid absorption from the diet. Mice lacking SLC6A19 show signs of protein restriction, have improved glucose tolerance, and are protected from diet-induced obesity. Pharmacological blockage of this transporter could be used to induce protein restriction and to treat metabolic diseases such as type 2 diabetes. A few novel inhibitors of SLC6A19 have recently been identified using in vitro compound screening, but it remains unclear whether these compounds block the transporter in vivo. To evaluate the efficacy of SLC6A19 inhibitors biomarkers are required that can reliably detect successful inhibition of the transporter in mice. A gas chromatography mass spectrometry (GC-MS)-based untargeted metabolomics approach was used to discriminate global metabolite profiles in plasma, urine and faecal samples from SLC6A19ko and wt mice. Due to inefficient absorption in the intestine and lack of reabsorption in the kidney, significantly elevated amino acids levels were observed in urine and faecal samples. By contrast, a few neutral amino acids were reduced in the plasma of male SLC6A19ko mice as compared to other biological samples. Metabolites of bacterial protein fermentation such as p-cresol glucuronide and 3-indole-propionic acid were more abundant in SLC6A19ko mice, indicating protein malabsorption of dietary amino acids. Consistently, plasma appearance rates of [14C]-labelled neutral amino acids were delayed in SLC6A19ko mice as compared to wt after intra-gastric administration of a mixture of amino acids. Receiver operating characteristic (ROC) curve analysis was used to validate the potential use of these metabolites as biomarkers. These findings provide putative metabolite biomarkers that can be used to detect protein malabsorption and the inhibition of this transporter in intestine and kidney.

scholarly journals Utilization of DC-SIGN for Entry of Feline Coronaviruses into Host Cells

2008 ◽  
Vol 82 (23) ◽  
pp. 11992-11996 ◽  
Author(s):  
Andrew D. Regan ◽  
Gary R. Whittaker
Keyword(s):  
Cell Line ◽  
Host Cells ◽  
3T3 Cells ◽  
Feline Infectious Peritonitis Virus ◽  
Feline Infectious Peritonitis ◽  
Feline Coronavirus

ABSTRACT The entry and dissemination of viruses in several families can be mediated by C-type lectins such as DC-SIGN. We showed that entry of the serotype II feline coronavirus strains feline infectious peritonitis virus (FIPV) WSU 79-1146 and DF2 into nonpermissive mouse 3T3 cells can be rescued by the expression of human DC-SIGN (hDC-SIGN) and that infection of a permissive feline cell line (Crandall-Reese feline kidney) was markedly enhanced by the overexpression of hDC-SIGN. Treatment with mannan considerably reduced infection of feline monocyte-derived cells expressing DC-SIGN, indicating a role for FIPV infection in vivo.

scholarly journals Concordance between Histology, Immunohistochemistry, and RT-PCR in the Diagnosis of Feline Infectious Peritonitis

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 852
Author(s):  
Angelica Stranieri ◽  
Donatella Scavone ◽  
Saverio Paltrinieri ◽  
Alessia Giordano ◽  
Federico Bonsembiante ◽  
...  
Keyword(s):  
Accurate Information ◽  
Rt Pcr ◽  
Likelihood Ratios ◽  
Predictive Values ◽  
Feline Infectious Peritonitis ◽  
Mesenteric Lymph ◽  
Polymerase Chain ◽  
Sensitivity Specificity ◽  
Feline Coronavirus

Histology, immunohistochemistry (IHC), and reverse transcription polymerase chain reaction (RT-PCR) have been used to diagnose feline infectious peritonitis (FIP), but no information regarding the comparison of their diagnostic performances on the same organ is available. The aims of this study were to determine the concordance among these tests and to evaluate which combination of tests and organs can be used in vivo. Histology, IHC, and nested RT-PCR (RT-nPCR) for feline coronavirus (FCoV) were performed on spleen, liver, mesenteric lymph node, kidney, large and small intestine, and lung from 14 FIP and 12 non-FIP cats. Sensitivity, specificity, predictive values, likelihood ratios, and concordance were calculated. IHC and RT-nPCR had the highest concordance in lung and liver, histology and IHC in the other organs. The sensitivity of histology, IHC, and RT-nPCR on the different organs ranged from 41.7 to 76.9%, 46.2 to 76.9%, and 64.3 to 85.7%, respectively, and their specificity ranged from 83.3 to 100.0%, 100% and 83.3 to 100.0%. Therefore, IHC is recommended when histology is consistent with FIP. If RT-nPCR is performed as the first diagnostic approach, results should always be confirmed with IHC. Lung or liver provide accurate information regardless of the method, while IHC is preferred to RT-nPCR to confirm FIP in the kidney or intestine.

Sign in / Sign up

Export Citation Format

Share Document