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Viruses
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Feline Viruses and Viral Diseases
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Feline Viruses and Viral Diseases

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 167724

Special Issue Editors

Prof. Dr. Julia A. Beatty

E-Mail Website
Guest Editor
Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, Australia
Interests: companion animal tumour virology; virus discovery; pathogenesis of chronic viral infections; feline retroviruses; feline gammaherpesviruses; feline hepadnavirus
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Katrin Hartmann

E-Mail Website
Guest Editor
Medizinischen Kleintierklinik, Centre of Clinical Veterinary Medicine, LMU Munich, Germany
Interests: infectious diseases in cats and dogs, specifically feline virus infections, leptospirosis, and canine vector-borne diseases as well as antiviral chemotherapy and vaccination/protection

Special Issue Information

Dear Colleagues,

The spectrum of feline disease syndromes linked to known or novel viruses is expanding. Understanding host–virus–environment interactions in domestic cats serves not just the welfare of this popular human companion but also that of susceptible sympatric felids, while providing insights into some human diseases.

Contemporary feline virology is underpinned by the discoveries of classical virologists, who likely never dreamed of high-throughput sequencing platforms. Such capabilities bring with them the imperative to nurture multidisciplinary approaches to make biological sense of the feline virome. Recently discovered homologues of human pathogens include feline morbilliviruses, a domestic cat hepadnavirus and a feline gammaherpesvirus. Working together, veterinary diagnosticians, epidemiologists, pathologists, molecular virologists, bioinformaticians, immunologists, and others will advance our understanding of whether, and under what circumstances, these and other novel viruses might act as feline pathogens, passengers, or symbionts.

Perplexing problems surrounding known feline viruses include triggers for the development of fatal feline infectious peritonitis, the re-emergence of feline panleukopenia virus, determinants of virulence among strains of feline calicivirus that cause virulent-systemic disease, the role of papillomaviruses in squamous cell carcinoma, the significance of regressive feline leukaemia virus for feline health, and many more.

Submissions are invited from researchers working in fields related to viruses and viral diseases of domestic cats and non-domestic felids. Studies that develop or envisage translational applications promoting feline health are particularly welcome.

Prof. Julia A. Beatty
Prof. Dr. Katrin Hartmann
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions. The editorial office is happy to offer 50% discount to the first 6 articles that are accepted for publication in this special issue.

Keywords

  • feline
  • cat
  • virus
  • pathogenesis
  • disease

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Published Papers (28 papers)

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Editorial

Jump to: Research, Review

5 pages, 185 KiB  
Editorial
Advances in Feline Viruses and Viral Diseases
by Julia A. Beatty and Katrin Hartmann
Viruses 2021, 13(5), 923; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050923 - 17 May 2021
Cited by 1 | Viewed by 3230
Abstract
Viral diseases play a very important role in feline medicine, and research on feline viruses and viral diseases is a well-established field that helps to safeguard the health of domestic cats and non-domestic felids, many of which are endangered [...] Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)

Research

Jump to: Editorial, Review

12 pages, 796 KiB  
Article
Feline Parvovirus Seroprevalence Is High in Domestic Cats from Disease Outbreak and Non-Outbreak Regions in Australia
by Elizabeth Jenkins, Conor Davis, Maura Carrai, Michael P. Ward, Susan O’Keeffe, Martine van Boeijen, Louise Beveridge, Costantina Desario, Canio Buonavoglia, Julia A. Beatty, Nicola Decaro and Vanessa R. Barrs
Viruses 2020, 12(3), 320; https://0-doi-org.brum.beds.ac.uk/10.3390/v12030320 - 16 Mar 2020
Cited by 12 | Viewed by 3862
Abstract
Multiple, epizootic outbreaks of feline panleukopenia (FPL) caused by feline parvovirus (FPV) occurred in eastern Australia between 2014 and 2018. Most affected cats were unvaccinated. We hypothesised that low population immunity was a major driver of re-emergent FPL. The aim of this study [...] Read more.
Multiple, epizootic outbreaks of feline panleukopenia (FPL) caused by feline parvovirus (FPV) occurred in eastern Australia between 2014 and 2018. Most affected cats were unvaccinated. We hypothesised that low population immunity was a major driver of re-emergent FPL. The aim of this study was to (i) determine the prevalence and predictors of seroprotective titres to FPV among shelter-housed and owned cats, and (ii) compare the prevalence of seroprotection between a region affected and unaffected by FPL outbreaks. FPV antibodies were detected by haemagglutination inhibition assay on sera from 523 cats and titres ≥1:40 were considered protective. Socioeconomic indices based on postcode and census data were included in the risk factor analysis. The prevalence of protective FPV antibody titres was high overall (94.3%), even though only 42% of cats were known to be vaccinated, and was not significantly different between outbreak and non-outbreak regions. On multivariable logistic regression analysis vaccinated cats were 29.94 times more likely to have protective FPV titres than cats not known to be vaccinated. Cats from postcodes of relatively less socioeconomic disadvantage were 5.93 times more likely to have protective FPV titres. The predictors identified for FPV seroprotective titres indicate targeted vaccination strategies in regions of socioeconomic disadvantage would be beneficial to increase population immunity. The critical level of vaccine coverage required to halt FPV transmission and prevent FPL outbreaks should be determined. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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9 pages, 2939 KiB  
Article
Identification of a Novel Papillomavirus Associated with Squamous Cell Carcinoma in a Domestic Cat
by Maura Carrai, Kate Van Brussel, Mang Shi, Ci-Xiu Li, Wei-Shan Chang, John S. Munday, Katja Voss, Alicia McLuckie, David Taylor, Andrew Laws, Edward C. Holmes, Vanessa R. Barrs and Julia A. Beatty
Viruses 2020, 12(1), 124; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010124 - 20 Jan 2020
Cited by 21 | Viewed by 9899
Abstract
Papillomaviruses infect the skin and mucosal surfaces of diverse animal hosts with consequences ranging from asymptomatic colonization to highly malignant epithelial cancers. Increasing evidence suggests a role for papillomaviruses in the most common cutaneous malignancy of domestic cats, squamous cell carcinoma (SCC). Using [...] Read more.
Papillomaviruses infect the skin and mucosal surfaces of diverse animal hosts with consequences ranging from asymptomatic colonization to highly malignant epithelial cancers. Increasing evidence suggests a role for papillomaviruses in the most common cutaneous malignancy of domestic cats, squamous cell carcinoma (SCC). Using total DNA sequencing we identified a novel feline papillomavirus in a nasal biopsy taken from a cat presenting with both nasal cavity lymphoma and recurrent squamous cell carcinoma affecting the nasal planum. We designate this novel virus as Felis catus papillomavirus 6 (FcaPV6). The complete FcaPV6 7453 bp genome was similar to those of other feline papillomaviruses and phylogenetic analysis revealed that it was most closely related to FcaPV3, although was distinct enough to represent a new viral type. Classification of FcaPV6 in a new genus alongside FcaPVs 3, 4 and 5 is supported. Archived excisional biopsy of the SCC, taken 20 months prior to presentation, was intensely positive on p16 immunostaining. FcaPV6, amplified using virus-specific, but not consensus, PCR, was the only papillomavirus detected in DNA extracted from the SCC. Conversely, renal lymphoma, sampled at necropsy two months after presentation, tested negative on FcaPV6-specific PCR. In sum, using metagenomics we demonstrate the presence of a novel feline papillomavirus in association with cutaneous squamous cell carcinoma. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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17 pages, 2933 KiB  
Article
miR-26a Inhibits Feline Herpesvirus 1 Replication by Targeting SOCS5 and Promoting Type I Interferon Signaling
by Jikai Zhang, Zhijie Li, Jiapei Huang, Hang Yin, Jin Tian and Liandong Qu
Viruses 2020, 12(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010002 - 18 Dec 2019
Cited by 15 | Viewed by 3065
Abstract
In response to viral infection, host cells activate various antiviral responses to inhibit virus replication. While feline herpesvirus 1 (FHV-1) manipulates the host early innate immune response in many different ways, the host could activate the antiviral response to counteract it through some [...] Read more.
In response to viral infection, host cells activate various antiviral responses to inhibit virus replication. While feline herpesvirus 1 (FHV-1) manipulates the host early innate immune response in many different ways, the host could activate the antiviral response to counteract it through some unknown mechanisms. MicroRNAs (miRNAs) which serve as a class of regulatory factors in the host, participate in the regulation of the host innate immune response against virus infection. In this study, we found that the expression levels of miR-26a were significantly upregulated upon FHV-1 infection. Furthermore, FHV-1 infection induced the expression of miR-26a via a cGAS-dependent pathway, and knockdown of cellular cGAS significantly blocked the expression of miR-26a induced by poly (dA:dT) or FHV-1 infection. Next, we investigated the biological function of miR-26a during viral infection. miR-26a was able to increase the phosphorylation of STAT1 and promote type I IFN signaling, thus inhibiting viral replication. The mechanism study showed that miR-26a directly targeted host SOCS5. Knockdown of SOCS5 increased the phosphorylation of STAT1 and enhanced the type I IFN-mediated antiviral response, and overexpression of suppressor of the cytokine signalling 5 (SOCS5) decreased the phosphorylation of STAT1 and inhibited the type I IFN-mediated antiviral response. Meanwhile, with the knockdown of SOCS5, the upregulated expression of phosphorylated STAT1 and the anti-virus effect induced by miR-26a were significantly inhibited. Taken together, our data demonstrated a new strategy of host miRNAs against FHV-1 infection by enhancing IFN antiviral signaling. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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20 pages, 5187 KiB  
Article
Distinct Lineages of Feline Parvovirus Associated with Epizootic Outbreaks in Australia, New Zealand and the United Arab Emirates
by Kate Van Brussel, Maura Carrai, Carrie Lin, Mark Kelman, Laura Setyo, Danielle Aberdein, Juliana Brailey, Michelle Lawler, Simone Maher, Ildiko Plaganyi, Emily Lewis, Adele Hawkswell, Andrew B. Allison, Joanne Meers, Vito Martella, Julia A. Beatty, Edward C. Holmes, Nicola Decaro and Vanessa R. Barrs
Viruses 2019, 11(12), 1155; https://0-doi-org.brum.beds.ac.uk/10.3390/v11121155 - 13 Dec 2019
Cited by 26 | Viewed by 5836
Abstract
Feline panleukopenia (FPL), a frequently fatal disease of cats, is caused by feline parvovirus (FPV) or canine parvovirus (CPV). We investigated simultaneous outbreaks of FPL between 2014 and 2018 in Australia, New Zealand and the United Arab Emirates (UAE) where FPL outbreaks had [...] Read more.
Feline panleukopenia (FPL), a frequently fatal disease of cats, is caused by feline parvovirus (FPV) or canine parvovirus (CPV). We investigated simultaneous outbreaks of FPL between 2014 and 2018 in Australia, New Zealand and the United Arab Emirates (UAE) where FPL outbreaks had not been reported for several decades. Case data from 989 cats and clinical samples from additional 113 cats were obtained to determine the cause of the outbreaks and epidemiological factors involved. Most cats with FPL were shelter-housed, 9 to 10 weeks old at diagnosis, unvaccinated, had not completed a primary vaccination series or had received vaccinations noncompliant with current guidelines. Analysis of parvoviral VP2 sequence data confirmed that all FPL cases were caused by FPV and not CPV. Phylogenetic analysis revealed that each of these outbreaks was caused by a distinct FPV, with two virus lineages present in eastern Australia and virus movement between different geographical locations. Viruses from the UAE outbreak formed a lineage of unknown origin. FPV vaccine virus was detected in the New Zealand cases, highlighting the difficulty of distinguishing the co-incidental shedding of vaccine virus in vaccinated cats. Inadequate vaccination coverage in shelter-housed cats was a common factor in all outbreaks, likely precipitating the multiple re-emergence of infection events. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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17 pages, 1891 KiB  
Article
Feline Infectious Peritonitis as a Systemic Inflammatory Disease: Contribution of Liver and Heart to the Pathogenesis
by Alexandra J Malbon, Sonja Fonfara, Marina L Meli, Shelley Hahn, Herman Egberink and Anja Kipar
Viruses 2019, 11(12), 1144; https://0-doi-org.brum.beds.ac.uk/10.3390/v11121144 - 10 Dec 2019
Cited by 15 | Viewed by 6451
Abstract
Feline infectious peritonitis (FIP) is a fatal immune-mediated disease of cats, induced by feline coronavirus (FCoV). A combination of as yet poorly understood host and viral factors combine to cause a minority of FCoV-infected cats to develop FIP. Clinicopathological features include fever, vasculitis, [...] Read more.
Feline infectious peritonitis (FIP) is a fatal immune-mediated disease of cats, induced by feline coronavirus (FCoV). A combination of as yet poorly understood host and viral factors combine to cause a minority of FCoV-infected cats to develop FIP. Clinicopathological features include fever, vasculitis, and serositis, with or without effusions; all of which indicate a pro-inflammatory state with cytokine release. As a result, primary immune organs, as well as circulating leukocytes, have thus far been of most interest in previous studies to determine the likely sources of these cytokines. Results have suggested that these tissues alone may not be sufficient to induce the observed inflammation. The current study therefore focussed on the liver and heart, organs with a demonstrated ability to produce cytokines and therefore with huge potential to exacerbate inflammatory processes. The IL-12:IL-10 ratio, a marker of the immune system’s inflammatory balance, was skewed towards the pro-inflammatory IL-12 in the liver of cats with FIP. Both organs were found to upregulate mRNA expression of the inflammatory triad of cytokines IL-1β, IL-6, and TNF-α in FIP. This amplifying step may be one of the missing links in the pathogenesis of this enigmatic disease. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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13 pages, 2938 KiB  
Article
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
by Sylvie Brunet, Cécile Sigoillot-Claude, Daniel Pialot and Hervé Poulet
Viruses 2019, 11(12), 1090; https://0-doi-org.brum.beds.ac.uk/10.3390/v11121090 - 23 Nov 2019
Cited by 23 | Viewed by 3932
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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12 pages, 1803 KiB  
Article
Survivin Overexpression Has a Negative Effect on Feline Calicivirus Infection
by Oscar Salvador Barrera-Vázquez, Clotilde Cancio-Lonches, Carlos Emilio Miguel-Rodríguez, Monica Margarita Valdes Pérez and Ana Lorena Gutiérrez-Escolano
Viruses 2019, 11(11), 996; https://0-doi-org.brum.beds.ac.uk/10.3390/v11110996 - 30 Oct 2019
Cited by 2 | Viewed by 2980
Abstract
It is known that levels of the anti-apoptotic protein survivin are reduced during Murine norovirus MNV-1 and Feline calicivirus (FCV) infection as part of the apoptosis establishment required for virus release and propagation in the host. Recently, our group has reported that overexpression [...] Read more.
It is known that levels of the anti-apoptotic protein survivin are reduced during Murine norovirus MNV-1 and Feline calicivirus (FCV) infection as part of the apoptosis establishment required for virus release and propagation in the host. Recently, our group has reported that overexpression of survivin causes a reduction of FCV protein synthesis and viral progeny production, suggesting that survivin may affect early steps of the replicative cycle. Using immunofluorescence assays, we observed that overexpression of survivin, resulted in the reduction of FCV infection not only in transfected but also in the neighboring nontransfected CrFK cells, thus suggesting autocrine and paracrine protective effects. Cells treated with the supernatants collected from CrFK cells overexpressing survivin showed a reduction in FCV but not MNV-1 protein production and viral yield, suggesting that FCV binding and/or entry were specifically altered. The reduced ability of FCV to bind to the surface of the cells overexpressing survivin, or treated with the supernatants collected from these cells, correlate with the reduction in the cell surface of the FCV receptor, the feline junctional adhesion molecule (fJAM) 1, while no effect was observed in the cells transfected with the pAm-Cyan vector or in cells treated with the corresponding supernatants. Moreover, the overexpression of survivin affects neither Vaccinia virus (VACV) production in CrFK cells nor MNV-1 virus production in RAW 267.4 cells, indicating that the effect is specific for FCV. All of these results taken together indicate that cells that overexpress survivin, or cell treatment with the conditioned medium from these cells, results in the reduction of the fJAM-1 molecule and, therefore, a specific reduction in FCV entry and infection. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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27 pages, 2818 KiB  
Article
Pan-European Study on the Prevalence of the Feline Leukaemia Virus Infection – Reported by the European Advisory Board on Cat Diseases (ABCD Europe)
by Nadine Studer, Hans Lutz, Claude Saegerman, Enikö Gönczi, Marina L. Meli, Gianluca Boo, Katrin Hartmann, Margaret J. Hosie, Karin Moestl, Séverine Tasker, Sándor Belák, Albert Lloret, Corine Boucraut-Baralon, Herman F. Egberink, Maria-Grazia Pennisi, Uwe Truyen, Tadeusz Frymus, Etienne Thiry, Fulvio Marsilio, Diane Addie, Manfred Hochleithner, Filip Tkalec, Zsuzsanna Vizi, Anna Brunetti, Boyko Georgiev, Louisa F. Ludwig-Begall, Flurin Tschuor, Carmel T. Mooney, Catarina Eliasson, Janne Orro, Helle Johansen, Kirsi Juuti, Igor Krampl, Kaspars Kovalenko, Jakov Šengaut, Cristina Sobral, Petra Borska, Simona Kovaříková and Regina Hofmann-Lehmannadd Show full author list remove Hide full author list
Viruses 2019, 11(11), 993; https://0-doi-org.brum.beds.ac.uk/10.3390/v11110993 - 29 Oct 2019
Cited by 51 | Viewed by 9784
Abstract
Feline leukaemia virus (FeLV) is a retrovirus associated with fatal disease in progressively infected cats. While testing/removal and vaccination led to a decreased prevalence of FeLV, recently, this decrease has reportedly stagnated in some countries. This study aimed to prospectively determine the prevalence [...] Read more.
Feline leukaemia virus (FeLV) is a retrovirus associated with fatal disease in progressively infected cats. While testing/removal and vaccination led to a decreased prevalence of FeLV, recently, this decrease has reportedly stagnated in some countries. This study aimed to prospectively determine the prevalence of FeLV viraemia in cats taken to veterinary facilities in 32 European countries. FeLV viral RNA was semiquantitatively detected in saliva, using RT-qPCR as a measure of viraemia. Risk and protective factors were assessed using an online questionnaire to report geographic, demographic, husbandry, FeLV vaccination, and clinical data. The overall prevalence of FeLV viraemia in cats visiting a veterinary facility, of which 10.4% were shelter and rescue cats, was 2.3% (141/6005; 95% CI: 2.0%–2.8%) with the highest prevalences in Portugal, Hungary, and Italy/Malta (5.7%–8.8%). Using multivariate analysis, seven risk factors (Southern Europe, male intact, 1–6 years of age, indoor and outdoor or outdoor-only living, living in a group of ≥5 cats, illness), and three protective factors (Northern Europe, Western Europe, pedigree cats) were identified. Using classification and regression tree (CART) analysis, the origin of cats in Europe, pedigree, and access to outdoors were important predictors of FeLV status. FeLV-infected sick cats shed more viral RNA than FeLV-infected healthy cats, and they suffered more frequently from anaemia, anorexia, and gingivitis/stomatitis than uninfected sick cats. Most cats had never been FeLV-vaccinated; vaccination rates were indirectly associated with the gross domestic product (GDP) per capita. In conclusion, we identified countries where FeLV was undetectable, demonstrating that the infection can be eradicated and highlighting those regions where awareness and prevention should be increased. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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14 pages, 1607 KiB  
Article
Effects of Regulatory T Cell Depletion on NK Cell Responses against Listeria monocytogenes in Feline Immunodeficiency Virus Infected Cats
by Rita D. Simões, Alora LaVoy and Gregg A. Dean
Viruses 2019, 11(11), 984; https://0-doi-org.brum.beds.ac.uk/10.3390/v11110984 - 24 Oct 2019
Cited by 2 | Viewed by 2754
Abstract
Regulatory T cells (Treg) are key players in the maintenance of peripheral tolerance, preventing autoimmune diseases and restraining chronic inflammatory diseases. Evidence suggests Treg cells and NK cells have important roles in feline immunodeficiency virus (FIV) pathogenesis; however, in vivo studies investigating the [...] Read more.
Regulatory T cells (Treg) are key players in the maintenance of peripheral tolerance, preventing autoimmune diseases and restraining chronic inflammatory diseases. Evidence suggests Treg cells and NK cells have important roles in feline immunodeficiency virus (FIV) pathogenesis; however, in vivo studies investigating the interplay between these two cell populations are lacking. We previously described innate immune defects in FIV-infected cats characterized by cytokine deficits and impaired natural killer cell (NK) and NK T cell (NKT) functions. In this study, we investigated whether in vivo Treg depletion by treatment with an anti-feline CD25 monoclonal antibody would improve the innate immune response against subcutaneous challenge with Listeria monocytogenes (Lm). Treg depletion resulted in an increased overall number of cells in Lm-draining lymph nodes and increased proliferation of NK and NKT cells in FIV-infected cats. Treg depletion did not normalize expression of perforin or granzyme A by NK and NKT cells, nor did Treg depletion result in improved clearance of Lm. Thus, despite the quantitative improvements in the NK and NKT cell responses to Lm, there was no functional improvement in the early control of Lm. CD1a+ dendritic cell percentages in the lymph nodes of FIV-infected cats were lower than in specific-pathogen-free control cats and failed to upregulate CD80 even when Treg were depleted. Taken together, Treg depletion failed to improve the innate immune response of FIV-infected cats against Lm and this may be due to dendritic cell dysfunction. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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8 pages, 3225 KiB  
Article
A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats
by Patricia A. Pesavento, Kenneth Jackson, Timothy Scase, Tiffany Tse, Bronte Hampson, John S. Munday, Vanessa R. Barrs and Julia A. Beatty
Viruses 2019, 11(10), 969; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100969 - 21 Oct 2019
Cited by 39 | Viewed by 7463
Abstract
In 2015, over 850,000 people died from chronic hepatitis and hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV). A novel hepatitis B-like virus has recently been identified in domestic cats. The pathogenic potential of domestic cat hepadnavirus (DCH), for which 6.5% to [...] Read more.
In 2015, over 850,000 people died from chronic hepatitis and hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV). A novel hepatitis B-like virus has recently been identified in domestic cats. The pathogenic potential of domestic cat hepadnavirus (DCH), for which 6.5% to 10.8% of pet cats are viremic, is unknown. We evaluated stored formalin-fixed, paraffin-embedded biopsies of diseased and normal feline liver for the presence of DCH using PCR and in situ hybridization (ISH). DCH was detected in 43% (6/14) of chronic hepatitis cases and 28% (8/29) of HCCs, whereas cholangitis (n = 6), biliary carcinoma (n = 18) and normal liver (n = 15) all tested negative for DCH. Furthermore, in DCH-associated cases, the histologic features of inflammation and neoplasia, and the viral distribution on ISH were strikingly similar to those seen with HBV-associated disease. Several histological features common in human HBV-associated hepatitis, including piecemeal necrosis and apoptotic bodies, were identified in DCH-positive cases of chronic hepatitis. In two cases of HCC examined, the proliferation index in regions that were ISH-positive was higher than in ISH-negative regions. The intracellular distribution of virus in both hepatitis and HCC demonstrated that viral nucleic acid is present in both nuclear and cytoplasmic forms. Collectively, these findings demonstrate a compelling association between DCH and some cases of chronic hepatitis and hepatocellular carcinoma in the cat that mirrors features of HBV-associated hepatopathies. Future investigations of viral epidemiology and natural history are needed to establish the impact of DCH on feline health. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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16 pages, 1369 KiB  
Article
Environmental Contamination and Hygienic Measures After Feline Calicivirus Field Strain Infections of Cats in a Research Facility
by Andrea Monika Spiri, Marina Luisa Meli, Barbara Riond, Imogen Herbert, Margaret J. Hosie and Regina Hofmann-Lehmann
Viruses 2019, 11(10), 958; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100958 - 17 Oct 2019
Cited by 14 | Viewed by 5320
Abstract
Feline calicivirus (FCV) can cause painful oral ulcerations, salivation, gingivitis/stomatitis, fever and depression in infected cats; highly virulent virus variants can lead to fatal epizootic outbreaks. Viral transmission occurs directly or indirectly via fomites. The aim of this study was to investigate the [...] Read more.
Feline calicivirus (FCV) can cause painful oral ulcerations, salivation, gingivitis/stomatitis, fever and depression in infected cats; highly virulent virus variants can lead to fatal epizootic outbreaks. Viral transmission occurs directly or indirectly via fomites. The aim of this study was to investigate the presence and viability of FCV in the environment after sequential oronasal infections of specified pathogen-free cats with two FCV field strains in a research facility. Replicating virus was detected in saliva swabs from all ten cats after the first and in four out of ten cats after the second FCV exposure using virus isolation to identify FCV shedders. In the environment, where cleaning, but no disinfection took place, FCV viral RNA was detectable using RT-qPCR on all tested items and surfaces, including cat hair. However, only very limited evidence was found of replicating virus using virus isolation. Viral RNA remained demonstrable for at least 28 days after shedding had ceased in all cats. Disinfection with 5% sodium bicarbonate (and IncidinTM Plus) and barrier measures were effective in that no viral RNA was detectable outside the cat rooms. Our findings are important for any multicat environment to optimize hygienic measures against FCV infection. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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15 pages, 2590 KiB  
Article
Interferon γ and α Have Differential Effects on SAMHD1, a Potent Antiviral Protein, in Feline Lymphocytes
by Peyman Asadian and Dorothee Bienzle
Viruses 2019, 11(10), 921; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100921 - 09 Oct 2019
Cited by 2 | Viewed by 2928
Abstract
Sterile alpha motif and histidine/aspartic domain-containing protein 1 (SAMHD1) is a protein with anti-viral, anti-neoplastic, and anti-inflammatory properties. By degrading cellular dNTPs to constituent deoxynucleoside and free triphosphate, SAMHD1 limits viral DNA synthesis and prevents replication of HIV-1 and some DNA viruses such [...] Read more.
Sterile alpha motif and histidine/aspartic domain-containing protein 1 (SAMHD1) is a protein with anti-viral, anti-neoplastic, and anti-inflammatory properties. By degrading cellular dNTPs to constituent deoxynucleoside and free triphosphate, SAMHD1 limits viral DNA synthesis and prevents replication of HIV-1 and some DNA viruses such as HBV, vaccinia, and HSV-1. Recent findings suggest SAMHD1 is broadly active against retroviruses in addition to HIV-1, such as HIV-2, FIV, BIV, and EIAV. Interferons are cytokines produced by lymphocytes and other cells that induce a wide array of antiviral proteins, including some with activity again lentiviruses. Here we evaluated the role of IFNs on SAMHD1 gene expression, transcription, and post-translational modification in a feline CD4+ T cell line (FeTJ) and in primary feline CD4+ T lymphocytes. SAMHD1 mRNA in FetJ cells increased in a dose-related manner in response to IFNγ treatment concurrent with increased nuclear localization and phosphorylation. IFNα treatment induced SAMHD1 mRNA but did not significantly alter SAMHD1 protein detection, phosphorylation, or nuclear translocation. In purified primary feline CD4+ lymphocytes, IL2 supplementation increased SAMHD1 expression, but the addition of IFNγ did not further alter SAMHD1 protein expression or nuclear localization. Thus, the effect of IFNγ on SAMHD1 expression is cell-type dependent, with increased translocation to the nucleus and phosphorylation in FeTJ but not primary CD4+ lymphocytes. These findings imply that while SAMH1 is inducible by IFNγ, overall activity is cell type and compartment specific, which is likely relevant to the establishment of lentiviral reservoirs in quiescent lymphocyte populations. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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14 pages, 1443 KiB  
Article
Mucosal Immune Response to Feline Enteric Coronavirus Infection
by Morgan Pearson, Alora LaVoy, Samantha Evans, Allison Vilander, Craig Webb, Barbara Graham, Esther Musselman, Jonathan LeCureux, Sue VandeWoude and Gregg A. Dean
Viruses 2019, 11(10), 906; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100906 - 27 Sep 2019
Cited by 15 | Viewed by 5224
Abstract
Feline infectious peritonitis is a devastating, fatal disease of domestic cats caused by a pathogenic mutant virus derived from the ubiquitous feline enteric coronavirus (FECV). Infection by FECV is generally subclinical, and little is known about the mucosal immune response that controls and [...] Read more.
Feline infectious peritonitis is a devastating, fatal disease of domestic cats caused by a pathogenic mutant virus derived from the ubiquitous feline enteric coronavirus (FECV). Infection by FECV is generally subclinical, and little is known about the mucosal immune response that controls and eliminates the virus. We investigated the mucosal immune response against FECV in an endemically infected breeding colony over a seven-month period. Thirty-three cats were grouped according to FECV seropositivity and fecal virus shedding into naïve/immunologically quiescent, convalescent and actively infected groups. Blood, fecal samples and colon biopsies were collected to assess the mucosal and systemic immunologic and virologic profile. Results showed that cats with active FECV infections have strong systemic IgG and mucosal IgA responses that wane after virus clearance. Significant FECV-specific mucosal T cell IFNγ responses were not detected in any of the three groups. A shift toward an inflammatory state in the mucosa was suggested by increased IL17:FoxP3 expression. However, no histologic abnormalities were observed, and no shifts in lymphocyte subpopulation phenotype or proliferation were noted. Together, the results suggest that control of FECV is mediated by humoral mucosal and systemic responses and that perturbations in the primary reservoir organ (colon) are minimal. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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13 pages, 1367 KiB  
Article
Follow-Up of Viral Parameters in FeLV- or FIV-Naturally Infected Cats Treated Orally with Low Doses of Human Interferon Alpha
by Esperanza Gomez-Lucia, Victorio M. Collado, Guadalupe Miró, Sonsoles Martín, Laura Benítez and Ana Doménech
Viruses 2019, 11(9), 845; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090845 - 11 Sep 2019
Cited by 9 | Viewed by 5035
Abstract
Specific treatments for the long-life infections by feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are either toxic, expensive or not too effective. Interferon α (IFN-α) is an immunomodulatory molecule which has been shown in vitro to decrease the release of infective [...] Read more.
Specific treatments for the long-life infections by feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are either toxic, expensive or not too effective. Interferon α (IFN-α) is an immunomodulatory molecule which has been shown in vitro to decrease the release of infective particles. The aim of this study was to follow the progress of the clinical score and viral parameters of FeLV- and FIV-naturally infected privately owned cats treated with recombinant human IFN-α (rHuIFN-α, Roferon-A). Twenty-seven FeLV-infected cats (FeLV+) and 31 FIV-infected cats (FIV+) were enrolled in the study. Owners were instructed to orally administer 1 mL/day of 60 IU rHuIFN-α/mL in alternating weeks for four months. Blood samples were taken at the beginning of the study (M0), mid-treatment (M2), end of treatment (M4), and 6–10 months later (M10). Clinical status at these time points improved notably with rHuIFN-α treatment, regardless of the initial severity of the disease, an effect which lasted throughout the study in most animals (15 of the 16 FeLV+ symptomatic cats; 20 of the 22 FIV+ symptomatic cats) improved markedly their clinical situation. In FeLV+ cats plasma antigenemia (p27CA), reverse transcriptase (RT) activity, and proviral load decreased at M2 and M4 but increased again at M10 (“rebound effect”). The level of antigenemia or RT activity was below the detection limits in FIV+ cats, and the effect on proviral load was less marked than in FeLV+ cats. Taken together, these results indicate that rHuIFN-α is a good candidate for treating FeLV+ cats, but the “rebound effect” seen when treatment was discontinued suggests that additional studies should be conducted to clarify its effect on progression of the infection in cats. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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17 pages, 3446 KiB  
Article
Expression of APOBEC3 Lentiviral Restriction Factors in Cats
by Ryan M. Troyer, Jennifer L. Malmberg, Xin Zheng, Craig Miller, Martha MacMillan, Wendy S. Sprague, Britta A. Wood and Sue VandeWoude
Viruses 2019, 11(9), 831; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090831 - 07 Sep 2019
Cited by 2 | Viewed by 3672
Abstract
Feline immunodeficiency virus (FIV) is a naturally occurring T-cell tropic lentiviral disease of felids with many similarities to HIV/AIDS in humans. Similar to primate lentiviral-host interactions, feline APOBEC3 (A3) has been shown to inhibit FIV infection in a host-specific manner and feline A3 [...] Read more.
Feline immunodeficiency virus (FIV) is a naturally occurring T-cell tropic lentiviral disease of felids with many similarities to HIV/AIDS in humans. Similar to primate lentiviral-host interactions, feline APOBEC3 (A3) has been shown to inhibit FIV infection in a host-specific manner and feline A3 degradation is mediated by FIV Vif. Further, infection of felids with non-native FIV strains results in restricted viral replication in both experimental and naturally occurring infections. However, the link between molecular A3-Vif interactions and A3 biological activity during FIV infection has not been well characterized. We thus examined expression of the feline A3 genes A3Z2, A3Z3 and A3Z2-Z3 during experimental infection of domestic cats with host-adapted domestic cat FIV (referred to as FIV) and non-adapted Puma concolor FIV (referred to as puma lentivirus, PLV). We determined A3 expression in different tissues and blood cells from uninfected, FIV-infected, PLV-infected and FIV/PLV co-infected cats; and in purified blood cell subpopulations from FIV-infected and uninfected cats. Additionally, we evaluated regulation of A3 expression by cytokines, mitogens, and FIV infection in cultured cells. In all feline cells and tissues studied, there was a striking difference in expression between the A3 genes which encode FIV inhibitors, with A3Z3 mRNA abundance exceeding that of A3Z2-Z3 by 300-fold or more. Interferon-alpha treatment of cat T cells resulted in upregulation of A3 expression, while treatment with interferon-gamma enhanced expression in cat cell lines. In cats, secondary lymphoid organs and peripheral blood mononuclear cells (PBMC) had the highest basal A3 expression levels and A3 genes were differentially expressed among blood T cells, B cells, and monocytes. Acute FIV and PLV infection of cats, and FIV infection of primary PBMC resulted in no detectable change in A3 expression with the exception of significantly elevated A3 expression in the thymus, the site of highest FIV replication. We conclude that cat A3 expression is regulated by cytokine treatment but, by and large, lentiviral infection did not appear to alter expression. Differences in A3 expression in different blood cell subsets did not appear to impact FIV viral replication kinetics within these cells. Furthermore, the relative abundance of A3Z3 mRNA compared to A3Z2-Z3 suggests that A3Z3 may be the major active anti-lentiviral APOBEC3 gene product in domestic cats. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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14 pages, 1705 KiB  
Article
The Conserved Tyr176/Leu177 Motif in the α-Helix 9 of the Feline Immunodeficiency Virus Capsid Protein Is Critical for Gag Particle Assembly
by César A. Ovejero, Silvia A. González and José L. Affranchino
Viruses 2019, 11(9), 816; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090816 - 04 Sep 2019
Cited by 4 | Viewed by 2904
Abstract
The capsid domain (CA) of the lentiviral Gag polyproteins has two distinct roles during virion morphogenesis. As a domain of Gag, it mediates the Gag–Gag interactions that drive immature particle assembly, whereas as a mature protein, it self-assembles into the conical core of [...] Read more.
The capsid domain (CA) of the lentiviral Gag polyproteins has two distinct roles during virion morphogenesis. As a domain of Gag, it mediates the Gag–Gag interactions that drive immature particle assembly, whereas as a mature protein, it self-assembles into the conical core of the mature virion. Lentiviral CA proteins are composed of an N-terminal region with seven α-helices and a C-terminal domain (CA-CTD) formed by four α-helices. Structural studies performed in HIV-1 indicate that the CA-CTD helix 9 establishes homodimeric interactions that contribute to the formation of the hexameric Gag lattice in immature virions. Interestingly, the mature CA core also shows inter-hexameric associations involving helix 9 residues W184 and M185. The CA proteins of feline immunodeficiency virus (FIV) and equine infectious anemia virus (EIAV) exhibit, at equivalent positions in helix 9, the motifs Y176/L177 and L169/F170, respectively. In this paper, we investigated the relevance of the Y176/L177 motif for FIV assembly by introducing a series of amino acid substitutions into this sequence and studying their effect on in vivo and in vitro Gag assembly, CA oligomerization, mature virion production, and viral infectivity. Our results demonstrate that the Y176/L177 motif in FIV CA helix 9 is essential for Gag assembly and CA oligomerization. Notably, mutations converting the FIV CA Y176/L177 motif into the HIV-1 WM and EIAV FL sequences allow substantial particle production and viral replication in feline cells. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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18 pages, 3715 KiB  
Article
Immunopathologic Effects of Prednisolone and Cyclosporine A on Feline Immunodeficiency Virus Replication and Persistence
by Craig Miller, Jordan Powers, Esther Musselman, Ryan Mackie, John Elder and Sue VandeWoude
Viruses 2019, 11(9), 805; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090805 - 30 Aug 2019
Cited by 5 | Viewed by 4049
Abstract
Feline immunodeficiency virus (FIV) induces opportunistic disease in chronically infected cats, and both prednisolone and cyclosporine A (CsA) are clinically used to treat complications such as lymphoma and stomatitis. However, the impact of these compounds on FIV infection are still unknown and understanding [...] Read more.
Feline immunodeficiency virus (FIV) induces opportunistic disease in chronically infected cats, and both prednisolone and cyclosporine A (CsA) are clinically used to treat complications such as lymphoma and stomatitis. However, the impact of these compounds on FIV infection are still unknown and understanding immunomodulatory effects on FIV replication and persistence is critical to guide safe and effective therapies. To determine the immunologic and virologic effects of prednisolone and CsA during FIV infection, FIV-positive cats were administered immunosuppressive doses of prednisolone (2 mg/kg) or CsA (5 mg/kg). Both prednisolone and CsA induced acute and transient increases in FIV DNA and RNA loads as detected by quantitative PCR. Changes in the proportion of lymphocyte immunophenotypes were also observed between FIV-infected and naïve cats treated with CsA and prednisolone, and both treatments caused acute increases in CD4+ lymphocytes that correlated with increased FIV RNA. CsA and prednisolone also produced alterations in cytokine expression that favored a shift toward a Th2 response. Pre-treatment with CsA slightly enhanced the efficacy of antiretroviral therapy but did not enhance clearance of FIV. Results highlight the potential for drug-induced perturbation of FIV infection and underscore the need for more information regarding immunopathologic consequences of therapeutic agents on concurrent viral infections. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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16 pages, 1494 KiB  
Article
Serological Screening for Coronavirus Infections in Cats
by Shan Zhao, Wentao Li, Nancy Schuurman, Frank van Kuppeveld, Berend-Jan Bosch and Herman Egberink
Viruses 2019, 11(8), 743; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080743 - 13 Aug 2019
Cited by 22 | Viewed by 8246
Abstract
Coronaviruses (CoVs) are widespread among mammals and birds and known for their potential for cross-species transmission. In cats, infections with feline coronaviruses (FCoVs) are common. Several non-feline coronaviruses have been reported to infect feline cells as well as cats after experimental infection, supported [...] Read more.
Coronaviruses (CoVs) are widespread among mammals and birds and known for their potential for cross-species transmission. In cats, infections with feline coronaviruses (FCoVs) are common. Several non-feline coronaviruses have been reported to infect feline cells as well as cats after experimental infection, supported by their ability to engage the feline receptor ortholog for cell entry. However, whether cats might become naturally infected with CoVs of other species is unknown. We analyzed coronavirus infections in cats by serological monitoring. In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Seventy-eight sera were positive for antibodies that recognized one or more coronavirus S1s whereas 1 serum exclusively reacted with human coronavirus 229E (HCoV-229E) and two sera exclusively reacted with porcine delta coronavirus (PDCoV). We observed antigenic cross-reactivity between S1s of type 1 and type 2 FCoVs, and between FCoV type 1 and porcine epidemic diarrhea virus (PEDV). Domain mapping of antibody epitopes indicated the presence of conserved epitope(s) particularly in the CD domains of S1. The cross-reactivity of FCoV type 1 and PEDV was also observed at the level of virus neutralization. To conclude, we provide the first evidence of antigenic cross-reactivity among S1 proteins of coronaviruses, which should be considered in the development of serological diagnoses. In addition, the potential role of cats in cross-species transmission of coronaviruses cannot be excluded. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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20 pages, 1693 KiB  
Article
Prevalence, Geographic Distribution, Risk Factors and Co-Infections of Feline Gammaherpesvirus Infections in Domestic Cats in Switzerland
by Marilisa Novacco, Neda Ranjbar Kohan, Martina Stirn, Marina L. Meli, Adrian Alberto Díaz-Sánchez, Felicitas S. Boretti and Regina Hofmann-Lehmann
Viruses 2019, 11(8), 721; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080721 - 06 Aug 2019
Cited by 10 | Viewed by 3278
Abstract
Recently, a gammaherpesvirus was described in domestic cats (FcaGHV1). The goal of the present study was to investigate the presence of FcaGHV1 in Swiss domestic cats and analyze potential risk factors. Blood samples from 881 cats presented to veterinarians in all Swiss cantons [...] Read more.
Recently, a gammaherpesvirus was described in domestic cats (FcaGHV1). The goal of the present study was to investigate the presence of FcaGHV1 in Swiss domestic cats and analyze potential risk factors. Blood samples from 881 cats presented to veterinarians in all Swiss cantons and from 91 stray cats and neoplastic tissue samples from 17 cats with lymphoma were evaluated. FcaGHV1 was detected by real-time PCR targeting the glycoprotein B gene, followed by sequencing. Blood samples were also tested for feline hemoplasmas, feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). The molecular prevalence of FcaGHV1 was 6.0% (95% confidence interval (CI), 4.5–7.8%) in cats presented to veterinarians and 5.5% (95% CI, 1.8–12.4%) in stray cats. FcaGHV1 PCR-positive cats originated from 19/26 Swiss cantons. Factors significantly associated with FcaGHV1 detection included male sex, age >3 years, nonpedigree status and co-infection with FIV and hemoplasmas. Moreover, FeLV viremia tended to be associated with FcaGHV1 detection. High FcaGHV1 blood loads were found more frequently in FeLV-viremic cats and less frequently in hemoplasma-infected cats than in uninfected cats. Clinical information was unavailable for most of the 881 cats, but leukemia, carcinoma and cardiomyopathy were reported in FcaGHV1-positive cats. None of the tissue samples from the 17 cats with lymphoma tested positive for FcaGHV1. Sequence analyses revealed homogeneity among the Swiss isolates and >99.7% identity to published FcaGHV1 sequences. In conclusion, FcaGHV1 is present in Switzerland with a similar prevalence in cats presented to veterinarians and in stray cats. The pathogenic potential of FcaGHV1 needs further evaluation. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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14 pages, 600 KiB  
Article
Antibody Response to Feline Calicivirus Vaccination in Healthy Adult Cats
by Michèle Bergmann, Stephanie Speck, Anna Rieger, Uwe Truyen and Katrin Hartmann
Viruses 2019, 11(8), 702; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080702 - 31 Jul 2019
Cited by 15 | Viewed by 5126
Abstract
This study evaluated the prevalence of feline calicivirus (FCV) antibodies and response to vaccination in healthy adult cats. Cats >1 year (n = 111) that had not been vaccinated within 12 months of enrollment in the study received a vaccine containing inactivated [...] Read more.
This study evaluated the prevalence of feline calicivirus (FCV) antibodies and response to vaccination in healthy adult cats. Cats >1 year (n = 111) that had not been vaccinated within 12 months of enrollment in the study received a vaccine containing inactivated FCV antigen strains 431 and G1. Antibodies were determined on Days 0, 7, and 28 by virus neutralization (VN) using FCV isolate KS20, and by broad spectrum blocking FCV enzyme-linked immunosorbent assay (ELISA). Factors associated with the presence of antibodies and vaccine response were determined by uni- and multivariate analysis. Pre-vaccination antibodies were detected in 62.2% of cats (CI95%: 52.9–70.1) by VN and in 77.2% (CI95%: 67.5–84.6) by ELISA. A ≥4-fold titer increase after vaccination was observed in 13.6% (CI95%: 8.3–21.4) of cats with VN and 33.7% (CI95%: 24.5–44.5) with ELISA. Factors associated with the presence of pre-vaccination VN antibodies were age (≥2 years; OR: 7.091; p = 0.022) and lack of previous vaccination (OR: 3.472; p = 0.014). The presence of pre-vaccination ELISA antibodies was associated with time since last vaccination (OR: 5.672; p = 0.043). Outdoor cats were more likely to have a ≥4-fold ELISA titer increase (OR: 5.556; p = 0.005). Many cats had pre-vaccination FCV antibodies, and their presence depended on previous vaccinations and increases with age. A ≥4-fold titer increase was rarely observed and was influenced by the lifestyle of the cat. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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19 pages, 377 KiB  
Article
Decreased Sensitivity of the Serological Detection of Feline Immunodeficiency Virus Infection Potentially Due to Imported Genetic Variants
by Julia Frankenfeld, Theres Meili, Marina L. Meli, Barbara Riond, A. Katrin Helfer-Hungerbuehler, Eva Bönzli, Benita Pineroli and Regina Hofmann-Lehmann
Viruses 2019, 11(8), 697; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080697 - 31 Jul 2019
Cited by 17 | Viewed by 4915
Abstract
Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats worldwide. Diagnosis usually relies on antibody screening by point-of-care tests (POCT), e.g., by enzyme-linked immunosorbent assays (ELISA), and confirmation using Western blot (WB). We increasingly observed ELISA-negative, WB-positive samples and aimed to substantiate [...] Read more.
Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats worldwide. Diagnosis usually relies on antibody screening by point-of-care tests (POCT), e.g., by enzyme-linked immunosorbent assays (ELISA), and confirmation using Western blot (WB). We increasingly observed ELISA-negative, WB-positive samples and aimed to substantiate these observations using 1194 serum/plasma samples collected from 1998 to 2019 primarily from FIV-suspect cats. While 441 samples tested positive and 375 tested negative by ELISA and WB, 81 samples had discordant results: 70 were false ELISA-negative (WB-positive) and 11 were false ELISA-positive (WB-negative); 297 ambiguous results were not analyzed further. The diagnostic sensitivity and specificity of the ELISA (82% and 91%, respectively) were lower than those reported in 1995 (98% and 97%, respectively). The diagnostic efficiency was reduced from 97% to 86%. False ELISA-negative samples originated mainly (54%) from Switzerland (1995: 0%). Sixty-four false ELISA-negative samples were available for POCT (SNAPTM/WITNESSR): five were POCT-positive. FIV RT-PCR was positive for two of these samples and was weakly positive for two ELISA- and POCT-negative samples. Low viral loads prohibited sequencing. Our results suggest that FIV diagnosis has become more challenging, probably due to increasing travel by cats and the introduction of new FIV isolates not recognized by screening assays. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
23 pages, 1322 KiB  
Article
The Diagnosis of Feline Leukaemia Virus (FeLV) Infection in Owned and Group-Housed Rescue Cats in Australia
by Mark Westman, Jacqueline Norris, Richard Malik, Regina Hofmann-Lehmann, Andrea Harvey, Alicia McLuckie, Martine Perkins, Donna Schofield, Alan Marcus, Mike McDonald, Michael Ward, Evelyn Hall, Paul Sheehy and Margaret Hosie
Viruses 2019, 11(6), 503; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060503 - 31 May 2019
Cited by 25 | Viewed by 6813
Abstract
A field study was undertaken to (i) measure the prevalence of feline leukaemia virus (FeLV) exposure and FeLV infection in a cross-section of healthy Australian pet cats; and (ii) investigate the outcomes following natural FeLV exposure in two Australian rescue facilities. Group 1 [...] Read more.
A field study was undertaken to (i) measure the prevalence of feline leukaemia virus (FeLV) exposure and FeLV infection in a cross-section of healthy Australian pet cats; and (ii) investigate the outcomes following natural FeLV exposure in two Australian rescue facilities. Group 1 (n = 440) consisted of healthy client-owned cats with outdoor access, predominantly from eastern Australia. Groups 2 (n = 38) and 3 (n = 51) consisted of a mixture of healthy and sick cats, group-housed in two separate rescue facilities in Sydney, Australia, tested following identification of index cases of FeLV infection in cats sourced from these facilities. Diagnostic testing for FeLV exposure/infection included p27 antigen testing using three different point-of-care FeLV kits and a laboratory-based ELISA, real-time polymerase chain reaction (qPCR) testing to detect FeLV proviral DNA in leukocytes, real-time reverse-transcription PCR (qRT-PCR) testing to detect FeLV RNA in plasma, and neutralising antibody (NAb) testing. Cats were classified as FeLV-uninfected (FeLV-unexposed and presumptively FeLV-abortive infections) or FeLV-infected (presumptively regressive and presumptively progressive infections). In Group 1, 370 FeLV-unexposed cats (370/440, 84%), 47 abortive infections (47/440, 11%), nine regressive infections (9/440, 2%), and two progressive infections (2/440, 0.5%) were identified, and 12 FeLV-uninfected cats (12/440, 3%) were unclassifiable as FeLV-unexposed or abortive infections due to insufficient samples available for NAb testing. In Groups 2 and 3, 31 FeLV-unexposed cats (31/89, 35%), eight abortive infections (8/89, 9%), 22 regressive infections (22/89; 25%), and 19 progressive infections (19/89; 21%) were discovered, and nine FeLV-uninfected cats (9/89; 10%) were unclassifiable due to insufficient samples available for NAb testing. One of the presumptively progressively-infected cats in Group 3 was likely a focal FeLV infection. Two other presumptively progressively-infected cats in Group 3 may have been classified as regressive infections with repeated testing, highlighting the difficulties associated with FeLV diagnosis when sampling cats at a single time point, even with results from a panel of FeLV tests. These results serve as a reminder to Australian veterinarians that the threat of FeLV to the general pet cat population remains high, thus vigilant FeLV testing, separate housing for FeLV-infected cats, and FeLV vaccination of at-risk cats is important, particularly in group-housed cats in shelters and rescue facilities, where outbreaks of FeLV infection can occur. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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15 pages, 2444 KiB  
Article
Identification of a Novel Gammaherpesvirus in Canada lynx (Lynx canadensis)
by Liam D. Hendrikse, Ankita Kambli, Caroline Kayko, Marta Canuti, Bruce Rodrigues, Brian Stevens, Jennifer Vashon, Andrew S. Lang, David B. Needle and Ryan M. Troyer
Viruses 2019, 11(4), 363; https://0-doi-org.brum.beds.ac.uk/10.3390/v11040363 - 20 Apr 2019
Cited by 8 | Viewed by 4318
Abstract
Gammaherpesviruses (GHVs) infect many animal species and are associated with lymphoproliferative disorders in some. Previously, we identified several novel GHVs in North American felids; however, a GHV had never been identified in Canada lynx (Lynx canadensis). We, therefore, hypothesized the existence [...] Read more.
Gammaherpesviruses (GHVs) infect many animal species and are associated with lymphoproliferative disorders in some. Previously, we identified several novel GHVs in North American felids; however, a GHV had never been identified in Canada lynx (Lynx canadensis). We, therefore, hypothesized the existence of an unidentified GHV in lynx. Using degenerate nested and subsequently virus-specific PCR, we amplified and sequenced 3.4 kb of DNA from a novel GHV in lynx, which we named Lynx canadensis gammaherpesvirus 1 (LcaGHV1). Phylogenetic analysis determined that LcaGHV1 is a distinct GHV species belonging to the genus Percavirus. We then estimated the prevalence of LcaGHV1 in lynx by developing a PCR-based assay and detected LcaGHV1 DNA in 36% (95% CI: 22–53%) of lynx spleen DNA samples from Maine, USA and 17% (95% CI: 8–31%) from Newfoundland, Canada. The LcaGHV1 DNA sequences from Maine and Newfoundland lynx were nearly identical to each other (two nucleotide substitutions in 3.4 kb), suggesting that the unique lynx subspecies present on the island of Newfoundland (Lynx canadensis subsolanus) is infected with virus that very closely resembles virus found in mainland lynx. The potential ecologic and pathologic consequences of this novel virus for Canada lynx populations warrant further study. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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Review

Jump to: Editorial, Research

10 pages, 682 KiB  
Review
Feline Morbillivirus, a New Paramyxovirus Possibly Associated with Feline Kidney Disease
by Eun Jin Choi, Victoria Ortega and Hector C. Aguilar
Viruses 2020, 12(5), 501; https://0-doi-org.brum.beds.ac.uk/10.3390/v12050501 - 01 May 2020
Cited by 12 | Viewed by 3801
Abstract
Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including in Hong Kong, Japan, Italy, US, Brazil, Turkey, UK, Germany, and Malaysia. FeMV is classified in [...] Read more.
Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including in Hong Kong, Japan, Italy, US, Brazil, Turkey, UK, Germany, and Malaysia. FeMV is classified in the Morbillivirus genus within the Paramyxoviridae family. FeMV research has focused primarily on determining the host range, symptoms, and characteristics of persistent infections in vitro. Importantly, there is a potential association between FeMV infection and feline kidney diseases, such as tubulointerstitial nephritis (TIN) and chronic kidney diseases (CKD), which are known to significantly affect feline health and survival. However, the tropism and viral entry mechanism(s) of FeMV remain unknown. In this review, we summarize the FeMV studies up to date, including the discoveries of various FeMV strains, basic virology, pathogenicity, and disease signs. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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14 pages, 3836 KiB  
Review
A Tale of Two Viruses: The Distinct Spike Glycoproteins of Feline Coronaviruses
by Javier A. Jaimes, Jean K. Millet, Alison E. Stout, Nicole M. André and Gary R. Whittaker
Viruses 2020, 12(1), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010083 - 10 Jan 2020
Cited by 86 | Viewed by 10720
Abstract
Feline coronavirus (FCoV) is a complex viral agent that causes a variety of clinical manifestations in cats, commonly known as feline infectious peritonitis (FIP). It is recognized that FCoV can occur in two different serotypes. However, differences in the S protein are much [...] Read more.
Feline coronavirus (FCoV) is a complex viral agent that causes a variety of clinical manifestations in cats, commonly known as feline infectious peritonitis (FIP). It is recognized that FCoV can occur in two different serotypes. However, differences in the S protein are much more than serological or antigenic variants, resulting in the effective presence of two distinct viruses. Here, we review the distinct differences in the S proteins of these viruses, which are likely to translate into distinct biological outcomes. We introduce a new concept related to the non-taxonomical classification and differentiation among FCoVs by analyzing and comparing the genetic, structural, and functional characteristics of FCoV and the FCoV S protein among the two serotypes and FCoV biotypes. Based on our analysis, we suggest that our understanding of FIP needs to consider whether the presence of these two distinct viruses has implications in clinical settings. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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35 pages, 878 KiB  
Review
Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature
by Sandra Felten and Katrin Hartmann
Viruses 2019, 11(11), 1068; https://0-doi-org.brum.beds.ac.uk/10.3390/v11111068 - 15 Nov 2019
Cited by 82 | Viewed by 24760
Abstract
Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline [...] Read more.
Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV) that vary fundamentally in their virulence, but are indistinguishable by a number of diagnostic methods. This review focuses on all important steps every veterinary practitioner has to deal with and new diagnostic tests that can be considered when encountering a cat with suspected FIP with the aim to establish a definitive diagnosis. It gives an overview on all available direct and indirect diagnostic tests and their sensitivity and specificity reported in the literature in different sample material. By providing summarized data for sensitivity and specificity of each diagnostic test and each sample material, which can easily be accessed in tables, this review can help to facilitate the interpretation of different diagnostic tests and raise awareness of their advantages and limitations. Additionally, diagnostic trees depict recommended diagnostic steps that should be performed in cats suspected of having FIP based on their clinical signs or clinicopathologic abnormalities. These steps can easily be followed in clinical practice. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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23 pages, 2312 KiB  
Review
Feline Virome—A Review of Novel Enteric Viruses Detected in Cats
by Barbara Di Martino, Federica Di Profio, Irene Melegari and Fulvio Marsilio
Viruses 2019, 11(10), 908; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100908 - 30 Sep 2019
Cited by 14 | Viewed by 4513
Abstract
Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have been associated with gastroenteritis in cats. In the last few years, noroviruses, kobuviruses, and novel parvoviruses have been repetitively detected [...] Read more.
Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have been associated with gastroenteritis in cats. In the last few years, noroviruses, kobuviruses, and novel parvoviruses have been repetitively detected in diarrheic cats as alone or in mixed infections with other pathogens, raising a number of questions, with particular regards to their pathogenic attitude and clinical impact. In the present article, the current available literature on novel potential feline enteric viruses is reviewed, providing a meaningful update on the etiology, epidemiologic, pathogenetic, clinical, and diagnostic aspects of the infections caused by these pathogens. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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