scholarly journals Feline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and in vitro Efficacy of Novel Antivirals in Australian Outbreaks

2021 ◽  
Author(s):  
Matteo Bordicchia ◽  
Tulio Machado Fumian ◽  
Kate Van Brussel ◽  
Alice G. Russo ◽  
Maura Carrai ◽  
...  
Keyword(s):  
Clinical Epidemiology ◽  
Systemic Disease ◽  
Feline Calicivirus ◽  
Metagenomic Sequencing ◽  
Event Analysis ◽  
Amino Acid Residues ◽  
Upper Respiratory Tract ◽  
E Region ◽  
Tract Disease

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2’-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino acid residues from the hypervariable E region of the capsid in the cultured viruses provided no support for the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4-0.6 µM, TI 21; 2CMC EC50, 2.7-5.3 µM, TI >18; NITD-008, 0.5 to 0.9 µM, TI >111. Investigation of these antivirals for treatment of FCV-VSD is warranted.

scholarly journals Feline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and In Vitro Efficacy of Novel Antivirals in Australian Outbreaks

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2040
Author(s):  
Matteo Bordicchia ◽  
Tulio Machado Fumian ◽  
Kate Van Brussel ◽  
Alice G. Russo ◽  
Maura Carrai ◽  
...  
Keyword(s):  
Clinical Epidemiology ◽  
Systemic Disease ◽  
Feline Calicivirus ◽  
Metagenomic Sequencing ◽  
Event Analysis ◽  
Amino Acid Residues ◽  
Upper Respiratory Tract ◽  
E Region ◽  
Tract Disease

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV-VSD have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2′-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino-acid residues from the hypervariable E region of the capsid in the cultured viruses did not support the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose–response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4–0.6 µM, TI = 21; 2CMC EC50, 2.7–5.3 µM, TI > 18; NITD-008, 0.5 to 0.9 µM, TI > 111. Investigation of these antivirals for the treatment of FCV-VSD is warranted.

Prevalence of feline herpesvirus-1, feline calicivirus, Chlamydophila felis and Mycoplasma felis DNA and associated risk factors in cats in Spain with upper respiratory tract disease, conjunctivitis and/or gingivostomatitis

2016 ◽  
Vol 19 (4) ◽  
pp. 461-469 ◽  
Author(s):  
Mireia Fernandez ◽  
Edgar G Manzanilla ◽  
Albert Lloret ◽  
Marta León ◽  
Jean-Christophe Thibault
Keyword(s):  
Risk Factors ◽  
Respiratory Tract ◽  
Feline Calicivirus ◽  
Upper Respiratory Tract ◽  
Respiratory Tract Disease ◽  
Feline Herpesvirus ◽  
Upper Respiratory ◽  
Herpesvirus 1 ◽  
Tract Disease ◽  
Clinical Conditions

Objectives Our objective was to perform the first multicentric study in Spain to evaluate the prevalence of feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), Chlamydophila felis and Mycoplasma felis in cats with upper respiratory tract disease (URTD), conjunctivitis and/or gingivostomatitis (GS) compared with control cats; and to evaluate risk factors for these clinical conditions. Methods Conjunctival and oropharyngeal swabs were collected and a questionnaire regarding signalment, lifestyle, vaccination history and clinical signs was obtained for each cat. Swabs were tested for each pathogen by real-time PCR. Results The study population consisted of 358 cats, including 98 control cats. Among the 260 diseased cats, 127 cats presented with URTD, 149 cats had conjunctivitis, 154 cats were suffering GS; many cats presented more than one clinical condition. The prevalence observed of FHV-1, FCV, C felis and M felis was, respectively, 28.3%, 48.0%, 20.5% and 46.5% in cats with URTD; 24.2%, 43.6%, 19.5% and 38.3% in cats with conjunctivitis; and 15.6%, 58.4%, 9.1% and 37.7% in cats with GS. Prevalences in the control group were 6.1%, 15.3%, 2.0% and 20.4%, respectively. Coinfections were common among all groups of cats. Risk factors were identified for all groups. FHV-1, FCV and C felis were associated with URTD and conjunctivitis. FCV was strongly associated with GS. M felis was present in a high percentage of the population in all groups, but its role in these clinical conditions remains uncertain. Vaccination was protective for URTD and GS but not for conjunctivitis. Conclusions and relevance This epidemiological study describes, for the first time, prevalence for FHV-1, FCV, C felis and M felis in Spain. In general, the prevalences found are similar to those reported in other countries. Factors associated with disease expression were also identified, which are relevant for practitioners.

scholarly journals Animal Models in Human Adenovirus Research

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1253
Author(s):  
Luca D. Bertzbach ◽  
Wing-Hang Ip ◽  
Thomas Dobner
Keyword(s):  
Animal Models ◽  
Clinical Symptoms ◽  
Cell Transformation ◽  
Human Adenovirus ◽  
Upper Respiratory Tract ◽  
Tree Shrews ◽  
Cotton Rats ◽  
In Vitro Systems ◽  
Tract Disease

Human adenovirus (HAdV) infections cause a wide variety of clinical symptoms, ranging from mild upper respiratory tract disease to lethal outcomes, particularly in immunocompromised individuals. To date, neither widely available vaccines nor approved antiadenoviral compounds are available to efficiently deal with HAdV infections. Thus, there is a need to thoroughly understand HAdV-induced disease, and for the development and preclinical evaluation of HAdV therapeutics and/or vaccines, and consequently for suitable standardizable in vitro systems and animal models. Current animal models to study HAdV pathogenesis, persistence, and tumorigenesis include rodents such as Syrian hamsters, mice, and cotton rats, as well as rabbits. In addition, a few recent studies on other species, such as pigs and tree shrews, reported promising data. These models mimic (aspects of) HAdV-induced pathological changes in humans and, although they are relevant, an ideal HAdV animal model has yet to be developed. This review summarizes the available animal models of HAdV infection with comprehensive descriptions of virus-induced pathogenesis in different animal species. We also elaborate on rodent HAdV animal models and how they contributed to insights into adenovirus-induced cell transformation and cancer.

scholarly journals Multiple Correspondence Analysis on Amino Acid Properties within the Variable Region of the Capsid Protein Shows Differences between Classical and Virulent Systemic Feline Calicivirus Strains

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1090 ◽  
Author(s):  
Sylvie Brunet ◽  
Cécile Sigoillot-Claude ◽  
Daniel Pialot ◽  
Hervé Poulet
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Correspondence Analysis ◽  
Conformational Changes ◽  
Multiple Correspondence Analysis ◽  
Systemic Disease ◽  
Feline Calicivirus ◽  
Upper Respiratory Tract ◽  
Acid Properties ◽  
Amino Acid Properties

Feline calicivirus (FCV) is a widespread and highly prevalent pathogen of domestic cats, responsible for mild upper respiratory tract disease. Outbreaks of severe virulent systemic disease (VSD) associated with FCV infection have been reported worldwide. VSD FCV strains have a broader tropism and cause a systemic vascular compromise. Despite clear differences in the pathogenesis of VSD and oral respiratory infections, attempts to identify specific molecular markers of VSD strains on the major capsid protein VP1 have failed. Region E of VP1 is responsible for the interaction with the cell receptor Junctional Adhesion Molecule JAM-1 (FeJAM-1) and with VP2 minor capsid protein during the entry of the virus. We carried out an original analysis on the sequences from region E of VSD and classical strains. A Multiple Correspondence Analysis was performed on a Boolean matrix built by coding sequences on the basis of their amino acid properties. For the first time, this approach was able to differentiate VSD and classical FCV. Seven remarkable residue positions were shown to be statistically significant for pathotype differentiation, mainly located in the N-terminal hypervariable part of region E. As structural analysis suggested an interaction of these residues with FeJAM-1 or VP2, post-binding events, and specific conformational changes may explain the difference of pathogenesis between pathotypes.

scholarly journals Potential Therapeutic Agents for Feline Calicivirus Infection

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 433 ◽  
Author(s):  
Tulio M. Fumian ◽  
Daniel Enosi Tuipulotu ◽  
Natalie E. Netzler ◽  
Jennifer H. Lun ◽  
Alice G. Russo ◽  
...  
Keyword(s):  
Cell Culture ◽  
High Throughput Screening ◽  
Polymerase Activity ◽  
In Vitro Assays ◽  
Feline Calicivirus ◽  
Upper Respiratory Tract ◽  
Direct Acting Antivirals ◽  
Ic50 Values ◽  
Direct Acting

Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV protease-polymerase protein, we established two in vitro assays to assess the inhibitory activity of compounds directly against the FCV protease or polymerase. Using this recombinant enzyme, we identified quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC50 values of 2.8 μM and 2.7 μM, respectively). We also demonstrate the inhibition of FCV protease activity by GC376 (IC50 of 18 µM). Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2′-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC50 values in the low micromolar range (0.6 μM and 2.5 μM, respectively). In conclusion, we established two in vitro assays that will accelerate the research for FCV antivirals and can be used for the high-throughput screening of direct-acting antivirals.

scholarly journals Investigation of Feline calicivirus infection in cats with upper respiratory tract disease in Diyarbakir, Turkey

2021 ◽  
Vol 58 ◽  
pp. e177172
Author(s):  
Nazan Baksi ◽  
Aynur Simsek
Keyword(s):  
Respiratory Tract ◽  
Feline Calicivirus ◽  
Nasal Discharge ◽  
Oral Lesions ◽  
Upper Respiratory Tract ◽  
Respiratory Tract Disease ◽  
Blood Samples ◽  
Upper Respiratory ◽  
Upper Respiratory Tract Disease ◽  
Tract Disease

Feline calicivirus is among the most common pathogenic microorganisms in upper respiratory tract disease (URTD) and oral lesions of cats. It leads to stomatitis, oral ulceration, ocular and nasal discharge, conjunctivitis, fever, lameness, anorexia, hypersalivation, pneumonia, respiratory distress, coughing, and depression in infected cats. This study aimed to determine the role of Feline calicivirus (FCV) in cats with the upper respiratory tract disease in the Diyarbakir region, Turkey, to provide treatment for infected cats and contribute to the disease prophylaxis. The study material consisted of 10 cats (control group) considered to be healthy according to the clinical examination and 20 cats with URTD that were not vaccinated against Feline calicivirus infection of different breeds, ages, and genders brought to Dicle University Veterinary Faculty Prof. Dr. Servet SEKIN Polyclinic with URTD. After routine clinical examinations of the animals, oral and conjunctival swabs and blood samples were taken. Hematological and biochemical analyzes of blood samples were performed. Swab samples were analyzed by the polymerase chain reaction (PCR) method for the diagnosis of the agent. Oral lesions, hypersalivation, ocular and nasal discharge, coughing, and breathing difficulties were seen in clinical examinations of cats with URTD. Feline calicivirus was detected in only one cat’s conjunctival swab sample in PCR analyses. As a result, we found that Feline calicivirus infection was present in cats with URTD in the Diyarbakir region, and 5% positivity was found in cats with clinical symptoms according to PCR analysis.

scholarly journals Haemophilus parasuis VtaA2 is involved in adhesion to extracellular proteins

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Mar Costa-Hurtado ◽  
Laura Garcia-Rodriguez ◽  
Sergi Lopez-Serrano ◽  
Virginia Aragon
Keyword(s):  
Respiratory Tract ◽  
Systemic Disease ◽  
Extracellular Proteins ◽  
In Vitro Assays ◽  
Haemophilus Parasuis ◽  
Upper Respiratory Tract ◽  
Passenger Domain ◽  
Virulent Strains ◽  
Upper Respiratory

Abstract Haemophilus parasuis is part of the microbiota of the upper respiratory tract in swine. However, virulent strains can cause a systemic disease known as Glässer’s disease. Several virulence factors have been described in H. parasuis including the virulence-associated trimeric autotransporters (VtaAs). VtaA2 is up-regulated during infection and is only found in virulent strains. In order to determine its biological function, the vtaA2 gene was cloned with its native promotor region in pACYC184, and the transformed Escherichia coli was used to perform functional in vitro assays. VtaA2 was found to have a role in attachment to plastic, mucin, BSA, fibronectin and collagen. As other VtaAs from H. parasuis, the passenger domain of VtaA2 contains collagen domains. In order to examine the contribution of the collagen repeats to VtaA2 function, a recombinant vtaA2 without the central collagen domains was obtained and named vtaA2OL. VtaA2OL showed similar capacity than VtaA2 to adhere to plastic, mucin, BSA, fibronectin and plasma but a reduced capacity to adhere to collagen, suggesting that the collagen domains of VtaA2 are involved in collagen attachment. No function in cell adhesion and invasion to epithelial alveolar cell line A549 or unspecific binding to primary alveolar macrophages was found. Likewise VtaA2 had no role in serum or phagocytosis resistance. We propose that VtaA2 mediates adherence to the host by binding to the mucin, found in the upper respiratory tract mucus, and to the extracellular matrix proteins, present in the connective tissue of systemic sites, such as the serosa.

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