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1.
Genes (Basel) ; 13(5)2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1875530

ABSTRACT

We investigated four cats with similar clinical skin-related signs strongly suggestive of Ehlers-Danlos syndrome (EDS). Cases no. 1 and 4 were unrelated and the remaining two cases, no. 2 and 3, were reportedly siblings. Histopathological changes were characterized by severely altered dermal collagen fibers. Transmission electron microscopy in one case demonstrated abnormalities in the collagen fibril organization and structure. The genomes of the two unrelated affected cats and one of the affected siblings were sequenced and individually compared to 54 feline control genomes. We searched for private protein changing variants in known human EDS candidate genes and identified three independent heterozygous COL5A1 variants. COL5A1 is a well-characterized candidate gene for classical EDS. It encodes the proα1 chain of type V collagen, which is needed for correct collagen fibril formation and the integrity of the skin. The identified variants in COL5A1 are c.112_118+15del or r.spl?, c.3514A>T or p.(Lys1172*), and c.3066del or p.(Gly1023Valfs*50) for cases no. 1, 2&3, and 4, respectively. They presumably all lead to nonsense-mediated mRNA decay, which results in haploinsufficiency of COL5A1 and causes the alterations of the connective tissue. The whole genome sequencing approach used in this study enables a refinement of the diagnosis for the affected cats as classical EDS. It further illustrates the potential of such experiments as a precision medicine approach in animals with inherited diseases.


Subject(s)
Ehlers-Danlos Syndrome , Animals , Cats/genetics , Collagen/genetics , Collagen Type V/genetics , Ehlers-Danlos Syndrome/genetics , Ehlers-Danlos Syndrome/veterinary , Exons
2.
Viruses ; 14(5)2022 04 28.
Article in English | MEDLINE | ID: covidwho-1875800

ABSTRACT

Immunocompromise is a common condition in cats, especially due to widespread infections with immunosuppressive viruses, such as feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV), but also due to chronic non-infectious diseases, such as tumours, diabetes mellitus, and chronic kidney disease, as well as treatment with immunosuppressive drugs, such as glucocorticoids, cyclosporins, or tumour chemotherapy. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of experts in feline medicine from eleven European countries, discusses the current knowledge and rationale for vaccination of immunocompromised cats. So far, there are few data available on vaccination of immunocompromised cats, and sometimes studies produce controversial results. Thus, this guideline summarizes the available scientific studies and fills in the gaps with expert opinion, where scientific studies are missing. Ultimately, this review aims to help veterinarians with their decision-making in how best to vaccinate immunocompromised cats.


Subject(s)
Immunodeficiency Virus, Feline , Leukemia Virus, Feline , Animals , Cats , Europe , Vaccination/veterinary
3.
Res Vet Sci ; 148: 52-64, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1867752

ABSTRACT

Of the numerous animal species affected by the SARS-CoV-2 virus, cats are one of the most susceptible, and cat-to-cat transmission has been described. Although cat-to-human infection has not, as yet, been demonstrated, preventive measures should be taken in order to avoid both viral infection in cats and transmission among them. In this respect, the application of an effective vaccine to at-risk populations would be a useful tool for controlling the disease in this species. Here, we test a new vaccine prototype based on the Spike protein of the virus in order to prevent infection and infectious virus shedding in cats. The vaccine employed in experimentation, and which is easily produced, triggered a strong neutralizing antibody response in vaccinated animals. In contrast to that which occurred with control animals, no infectious virus was detected in the oropharyngeal or rectal swabs of vaccinated cats submitted to a SARS-CoV-2 challenge. These results are of great interest as regards future considerations related to implementing vaccination programs in pets. The value of cats as vaccination trial models is also described herein.


Subject(s)
COVID-19 , Cat Diseases , Animals , Antibodies, Neutralizing , COVID-19/prevention & control , COVID-19/veterinary , Cat Diseases/prevention & control , Cats , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Subunit , Virus Shedding
4.
Emerg Infect Dis ; 28(6): 1154-1162, 2022 06.
Article in English | MEDLINE | ID: covidwho-1862554

ABSTRACT

We tested swab specimens from pets in households in Ontario, Canada, with human COVID-19 cases by quantitative PCR for SARS-CoV-2 and surveyed pet owners for risk factors associated with infection and seropositivity. We tested serum samples for spike protein IgG and IgM in household pets and also in animals from shelters and low-cost neuter clinics. Among household pets, 2% (1/49) of swab specimens from dogs and 7.7% (5/65) from cats were PCR positive, but 41% of dog serum samples and 52% of cat serum samples were positive for SARS-CoV-2 IgG or IgM. The likelihood of SARS-CoV-2 seropositivity in pet samples was higher for cats but not dogs that slept on owners' beds and for dogs and cats that contracted a new illness. Seropositivity in neuter-clinic samples was 16% (35/221); in shelter samples, 9.3% (7/75). Our findings indicate a high likelihood for pets in households of humans with COVID-19 to seroconvert and become ill.


Subject(s)
COVID-19 , Cat Diseases , Dog Diseases , Animals , COVID-19/epidemiology , COVID-19/veterinary , Cat Diseases/epidemiology , Cats , Dog Diseases/diagnosis , Dog Diseases/epidemiology , Dogs , Immunoglobulin G , Immunoglobulin M , Ontario/epidemiology , Pets , Risk Factors , SARS-CoV-2
5.
Sci Rep ; 12(1): 8403, 2022 May 19.
Article in English | MEDLINE | ID: covidwho-1852501

ABSTRACT

In June-September 2021, we investigated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections in domestic dogs and cats (n = 225) in Bangkok and the vicinities, Thailand. SARS-CoV-2 was detected in a dog and a cat from COVID-19 positive households. Whole genome sequence analysis identified SARS-CoV-2 delta variant of concern (B.1.617.2). Phylogenetic analysis showed that SARS-CoV-2 isolated from dog and cat were grouped into sublineage AY.30 and AY.85, respectively. Antibodies against SARS-CoV-2 could be detected in both dog (day 9) and cat (day 14) after viral RNA detection. This study raises awareness on spill-over of variant of concern in domestic animals due to human-animal interface. Thus, surveillance of SARS-CoV-2 in domestic pets should be routinely conducted.


Subject(s)
COVID-19 , Cat Diseases , Dog Diseases , Animals , COVID-19/epidemiology , COVID-19/veterinary , Cat Diseases/diagnosis , Cat Diseases/epidemiology , Cats , Dog Diseases/diagnosis , Dog Diseases/epidemiology , Dogs , Phylogeny , SARS-CoV-2/genetics , Thailand/epidemiology
6.
Mem Inst Oswaldo Cruz ; 117: e210375, 2022.
Article in English | MEDLINE | ID: covidwho-1841186

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus of zoonotic origin that can bind to ACE2 receptors on the cells of many wild and domestic mammals. Studies have shown that the virus can circulate among animals mutate, lead to animal-to-human zoonotic jump, and further onward spread between humans. Infection in pets is unusual, and there are few human-to-pet transmission reports worldwide. OBJECTIVE: To describe the SARS-CoV-2 infection in a domestic animal in Córdoba, Colombian Caribbean region. METHODS: A cross-sectional molecular surveillance study was carried out, oral and rectal swabs were taken from cats and dogs living with people diagnosed with coronavirus disease 2019 (COVID-19). RESULTS: SARS-CoV-2 was found in a cat living with a person with COVID-19. Genome sequencing showed that the B.1.111 lineage caused the infection in the cat. The owner's sample could not be sequenced. The lineage is predominant in Colombia, and this variant is characterised by the presence of the D614D and Q57H mutation. CONCLUSION: The present work is the first report of an infected cat with SARS-CoV-2 with whole-genome sequencing in Colombia. It highlights the importance of detecting SARS-CoV-2 mutations that could promote the transmissibility of this new coronavirus. There is still a significant information gap on human-to-cat-to-human infection; we encourage self-isolation measures between COVID-19 patients and companion animals. The findings of this study give a preliminary view of the current panorama of SARS-CoV-2 infection in animals in Colombia.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , COVID-19/diagnosis , COVID-19/veterinary , Cats , Colombia/epidemiology , Cross-Sectional Studies , Dogs , Humans , Mammals/genetics , SARS-CoV-2/genetics , Whole Genome Sequencing
7.
Viruses ; 14(4)2022 03 23.
Article in English | MEDLINE | ID: covidwho-1834917

ABSTRACT

In recent years, advances in diagnostics and deep sequencing technologies have led to the identification and characterization of novel viruses in cats as protoparviruses and chaphamaparvoviruses, unveiling the diversity of the feline virome in the respiratory tract. Observational, epidemiological and experimental data are necessary to demonstrate firmly if some viruses are able to cause disease, as this information may be confounded by virus- or host-related factors. Also, in recent years, researchers were able to monitor multiple examples of transmission to felids of viruses with high pathogenic potential, such as the influenza virus strains H5N1, H1N1, H7N2, H5N6 and H3N2, and in the late 2019, the human hypervirulent coronavirus SARS-CoV-2. These findings suggest that the study of viral infections always requires a multi-disciplinary approach inspired by the One Health vision. By reviewing the literature, we provide herewith an update on the emerging viruses identified in cats and their potential association with respiratory disease.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H5N1 Subtype , Influenza, Human , Orthomyxoviridae Infections , Animals , COVID-19/veterinary , Cats , Humans , Influenza A Virus, H3N2 Subtype , Influenza A Virus, H7N2 Subtype , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/veterinary , SARS-CoV-2/genetics
8.
PLoS One ; 16(4): e0250853, 2021.
Article in English | MEDLINE | ID: covidwho-1833535

ABSTRACT

BACKGROUND: Infection by SARS-CoV-2 in domestic animals has been related to close contact with humans diagnosed with COVID-19. Objectives: To assess the exposure, infection, and persistence by SARS-CoV-2 of dogs and cats living in the same households of humans that tested positive for SARS-CoV-2, and to investigate clinical and laboratory alterations associated with animal infection. METHODS: Animals living with COVID-19 patients were longitudinally followed and had nasopharyngeal/oropharyngeal and rectal swabs collected and tested for SARS-CoV-2. Additionally, blood samples were collected for laboratory analysis, and plaque reduction neutralization test (PRNT90) to investigate specific SARS-CoV-2 antibodies. RESULTS: Between May and October 2020, 39 pets (29 dogs and 10 cats) of 21 patients were investigated. Nine dogs (31%) and four cats (40%) from 10 (47.6%) households were infected with or seropositive for SARS-CoV-2. Animals tested positive from 11 to 51 days after the human index COVID-19 case onset of symptoms. Three dogs tested positive twice within 14, 30, and 31 days apart. SARS-CoV-2 neutralizing antibodies were detected in one dog (3.4%) and two cats (20%). In this study, six out of thirteen animals either infected with or seropositive for SARS-CoV-2 have developed mild but reversible signs of the disease. Using logistic regression analysis, neutering, and sharing bed with the ill owner were associated with pet infection. CONCLUSIONS: The presence and persistence of SARS-CoV-2 infection have been identified in dogs and cats from households with human COVID-19 cases in Rio de Janeiro, Brazil. People with COVID-19 should avoid close contact with their pets during the time of their illness.


Subject(s)
COVID-19/epidemiology , COVID-19/veterinary , Pets/virology , Animals , Animals, Domestic/virology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Brazil/epidemiology , Cat Diseases , Cats , Dog Diseases , Dogs , Longitudinal Studies , Prevalence , SARS-CoV-2/pathogenicity
9.
Viruses ; 14(5)2022 04 21.
Article in English | MEDLINE | ID: covidwho-1822445

ABSTRACT

(1) Background: Feline coronavirus infection (FCoV) is common in multi-cat environments. A role of FCoV in causing diarrhea is often assumed, but has not been proven. The aim of this study was to evaluate an association of FCoV infection with diarrhea in multi-cat environments. (2) Methods: The study included 234 cats from 37 catteries. Fecal samples were analyzed for FCoV RNA by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Potential co-infections were determined by applying a qPCR panel on different potential enteropathogens and fecal flotation. A fecal scoring system was used to categorize feces as diarrheic or non-diarrheic. (3) Results: Of the 234 cats included, 23 had diarrhea. The prevalence of FCoV infection was 87.0% in cats with and 58.8% in cats without diarrhea. FCoV infection was significantly associated with diarrhea (Odds Ratio (OR) 5.01; p = 0.008). In addition, presence of Clostridium perfringens α toxin (OR 6.93; p = 0.032) and feline panleukopenia virus (OR 13.74; p = 0.004) were associated with an increased risk of diarrhea. There was no correlation between FCoV load and fecal score. FCoV-positive cats with co-infections were not more likely to have diarrhea than FCoV-positive cats without co-infections (p = 0.455). (4) Conclusions: FCoV infection is common in cats from catteries and can be associated with diarrhea.


Subject(s)
Coinfection , Coronavirus, Feline , Feline Infectious Peritonitis , Animals , Cats , Coinfection/veterinary , Coronavirus, Feline/genetics , Diarrhea/epidemiology , Diarrhea/veterinary , Feces , Feline Infectious Peritonitis/epidemiology
10.
Viruses ; 14(5)2022 04 21.
Article in English | MEDLINE | ID: covidwho-1822442

ABSTRACT

A canine coronavirus (CCoV) has now been reported from two independent human samples from Malaysia (respiratory, collected in 2017-2018; CCoV-HuPn-2018) and Haiti (urine, collected in 2017); these two viruses were nearly genetically identical. In an effort to identify any novel adaptations associated with this apparent shift in tropism we carried out detailed evolutionary analyses of the spike gene of this virus in the context of related Alphacoronavirus 1 species. The spike 0-domain retains homology to CCoV2b (enteric infections) and Transmissible Gastroenteritis Virus (TGEV; enteric and respiratory). This domain is subject to relaxed selection pressure and an increased rate of molecular evolution. It contains unique amino acid substitutions, including within a region important for sialic acid binding and pathogenesis in TGEV. Overall, the spike gene is extensively recombinant, with a feline coronavirus type II strain serving a prominent role in the recombinant history of the virus. Molecular divergence time for a segment of the gene where temporal signal could be determined, was estimated at around 60 years ago. We hypothesize that the virus had an enteric origin, but that it may be losing that particular tropism, possibly because of mutations in the sialic acid binding region of the spike 0-domain.


Subject(s)
Coronavirus, Canine , Animals , Cats , Dogs , N-Acetylneuraminic Acid , Spike Glycoprotein, Coronavirus/genetics , Tropism , Zoonoses
11.
Viruses ; 14(4)2022 03 25.
Article in English | MEDLINE | ID: covidwho-1822441

ABSTRACT

Cats have been shown to be highly susceptible to SARS-CoV-2, and transmission within the species has been demonstrated experimentally. In cats undergoing natural SARS-CoV-2 infections, human-to-animal transmission was mostly suspected. It can be postulated that, in stray cats with no or only minimal contact with humans, SARS-CoV-2 may pose a minor risk. The current study investigated the prevalence of active SARS-CoV-2 infections in Swiss stray cats using quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR). Saliva swabs from 1405 stray cats were collected in 14 Swiss cantons. The animals were sampled between February 2019 and February 2020 (pre-COVID-19 cohort: 523 cats) and between February 2020 and August 2021 (COVID-19 cohort: 882 cats). All the samples were tested by RT-qPCR, amplifying the envelope (E) gene and, in case of positive or inconclusive results, the RNA-dependent RNA polymerase (RdRp) gene of SARS-CoV-2. No SARS-CoV-2 viral RNA could be detected in any of the tested saliva swab samples. Our findings support the assumption that SARS-CoV-2 infections in stray cats are not highly prevalent in Switzerland. Nevertheless, the monitoring of stray cats and other susceptible animal species is necessary, since the "One Health" approach has been recognized as being essential to successfully fight the COVID-19 pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , COVID-19/diagnosis , COVID-19/epidemiology , Cats , Humans , Pandemics , RNA, Viral/genetics , SARS-CoV-2/genetics , Saliva , Switzerland/epidemiology
12.
Gene ; 825: 146443, 2022 May 30.
Article in English | MEDLINE | ID: covidwho-1814426

ABSTRACT

Both feline coronavirus (FCoV) and SARS-CoV-2 are coronaviruses that infect cats and humans, respectively. However, cats have been shown to be susceptible to SARS-CoV-2, and FCoV also had been shown to infect human. To elucidate the relationship between FCoV and SARS-CoV-2, we highlight the main characteristics of the genome, the receptor usage, and the correlation of the receptor-binding domain (RBD) of spike proteins in FCoV and SARS-CoV-2. It is demonstrated that FCoV and SARS-CoV-2 are closely related to the main characteristics of the genome, receptor usage, and RBD of spike proteins with similar furin cleavage sites. In particular, the affinity of the conserved feline angiotensin-converting enzyme 2 (fACE2) receptor to the RBD of SARS-CoV-2 suggests that cats are susceptible to SARS-CoV-2. In addition, cross-species of coronaviruses between cats and humans or other domesticated animals are also discussed. This review sheds light on cats as potential intermediate hosts for SARS-CoV-2 transmission, and cross-species transmission or zoonotic infection of FCoV and SARS-CoV-2 between cats and humans was identified.


Subject(s)
COVID-19 , Coronavirus, Feline , Animals , COVID-19/veterinary , Cats , Coronavirus, Feline/genetics , Coronavirus, Feline/metabolism , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
13.
Front Immunol ; 13: 857322, 2022.
Article in English | MEDLINE | ID: covidwho-1809402

ABSTRACT

Carnivores such as cats and minks are highly susceptible to SARS-CoV-2. Brazil is a global COVID-19 hot spot and several cases of human-to-cat transmission have been documented. We investigated the spread of SARS-CoV-2 by testing 547 domestic cats sampled between July-November 2020 from seven states in southern, southeastern, and northeastern Brazil. Moreover, we investigated whether immune responses elicited by enzootic coronaviruses affect SARS-CoV-2 infection in cats. We found infection with significantly higher neutralizing antibody titers against the Gamma variant of concern, endemic in Brazil during 2020, than against an early SARS-CoV-2 B.1 isolate (p<0.0001), validating the use of Gamma for further testing. The overall SARS-CoV-2 seroprevalence in Brazilian cats during late 2020 validated by plaque reduction neutralization test (PRNT90) was 7.3% (95% CI, 5.3-9.8). There was no significant difference in SARS-CoV-2 seroprevalence in cats between Brazilian states, suggesting homogeneous infection levels ranging from 4.6% (95% CI, 2.2-8.4) to 11.4% (95% CI, 6.7-17.4; p=0.4438). Seroprevalence of the prototypic cat coronavirus Feline coronavirus (FCoV) in a PRNT90 was high at 33.3% (95% CI, 24.9-42.5) and seroprevalence of Bovine coronavirus (BCoV) was low at 1.7% (95% CI, 0.2-5.9) in a PRNT90. Neutralizing antibody titers were significantly lower for FCoV than for SARS-CoV-2 (p=0.0001), consistent with relatively more recent infection of cats with SARS-CoV-2. Neither the magnitude of SARS-CoV-2 antibody titers (p=0.6390), nor SARS-CoV-2 infection status were affected by FCoV serostatus (p=0.8863). Our data suggest that pre-existing immunity against enzootic coronaviruses neither prevents, nor enhances SARS-CoV-2 infection in cats. High SARS-CoV-2 seroprevalence already during the first year of the pandemic substantiates frequent infection of domestic cats and raises concerns on potential SARS-CoV-2 mutations escaping human immunity upon spillback.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Brazil/epidemiology , COVID-19/epidemiology , COVID-19/veterinary , Cats , Cattle , Seroepidemiologic Studies
14.
J Vet Intern Med ; 36(2): 532-540, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1799262

ABSTRACT

BACKGROUND: Infection with Bartonella species is common in cats but reported effects of bacteremia on laboratory variables differ. OBJECTIVES: Evaluate for associations between Bartonella bacteremia and CBC and serum biochemical changes in sick and healthy cats throughout the United States. ANIMALS: A total of 3964 client-owned cats. METHODS: Retrospective cohort study using submissions to a commercial laboratory between 2011 and 2017. Serum biochemistry and CBC abnormalities (categorized as above or below reference intervals), age, and location (high- or low-risk state for Ctenocephalides felis) in presumed healthy and sick cats were evaluated for associations with presence of Bartonella spp. DNA, detected by PCR. Univariate and multivariable logistic regression analyses were performed. RESULTS: Bartonella spp. DNA was amplified from 127 (3.2%) of 3964 cats; 126 (99.2%) of 127 were from high flea risk states and 121 (95.3%) of 127 were presumed sick. Fever of unknown origin was the most common PCR panel requested. In the multivariable analysis, neutrophilia, decreased ALP activity, clinical status (presumed sick), and young age (≤2 years) each were positively associated whereas neutropenia and hyperproteinemia both were negatively associated with Bartonella spp. bacteremia. Presence of Bartonella spp. DNA had no association with test results for other infectious disease agents. CONCLUSIONS AND CLINICAL IMPORTANCE: In both healthy and sick cats, active Bartonella infections had minimal association with clinically relevant laboratory abnormalities. However, based on these results, in areas considered high risk for C. felis, active infection with Bartonella spp. is a reasonable differential diagnosis for cats presented with unexplained fever and neutrophilia, particularly if the cat is young.


Subject(s)
Bartonella Infections , Bartonella , Cat Diseases , Animals , Bartonella/genetics , Bartonella Infections/veterinary , Blood Cell Count/veterinary , Cats , DNA , Humans , Retrospective Studies
15.
Biomed Res Int ; 2022: 9627961, 2022.
Article in English | MEDLINE | ID: covidwho-1789057

ABSTRACT

Purpose: To report the first complete fox coronavirus (CoV) genome sequence obtained through genome-wide amplifications and to understand the adaptive evolution of fox CoV. Methods: Anal swab samples were collected from 35 foxes to detect the presence of CoV and obtain the virus sequence. Phylogenetic analysis was conducted using MrBayes. The possibility of recombination within these sequences was assessed using GARD. Analysis of the levels of selection pressure experienced by these sequences was assessed using methods on both the PAML and Data Monkey platforms. Results: Of the 35 samples, two were positive, and complete genome sequences for the viruses were obtained. Phylogenetic analysis, using Bayesian methods, of these sequences, together with other CoV sequences, revealed that the fox CoV sequences clustered with canine coronavirus (CCoV) sequences, with sequences from other carnivores more distantly related. In contrast to the feline, ferret and mink CoV sequences that clustered into species-specific clades, the fox CoV fell within the CCoV clade. Minimal evidence for recombination was found among the sequences. A total of 7, 3, 14, and 2 positively selected sites were identified in the M, N, S, and 7B genes, respectively, with 99, 111, and 581 negatively selected sites identified in M, N, and S genes, respectively. Conclusion: The complete genome sequence of fox CoV has been obtained for the first time. The results suggest that the genome sequence of fox CoV may have experienced adaptive evolution in the genes replication, entry, and virulence. The number of sites in each gene that experienced negative selection is far greater than the number that underwent positive selection, suggesting that most of the sequence is highly conserved and important for viral survive. However, positive selection at a few sites likely aided these viruses to adapt to new environments.


Subject(s)
Coronavirus Infections , Coronavirus, Canine , Coronavirus , Animals , Bayes Theorem , Cats , Coronavirus/genetics , Coronavirus Infections/genetics , Coronavirus, Canine/genetics , Dogs , Ferrets/genetics , Genome, Viral/genetics , Phylogeny , Sequence Analysis, DNA
16.
J Vet Sci ; 23(2): e27, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1776501

ABSTRACT

BACKGROUND: The role of Toll-like receptors (TLRs) in a feline infectious peritonitis virus (FIPV) infection is not completely understood. OBJECTIVES: This study examined the expression of TLR3, TLR7, TLR9, tumor necrosis factor-alpha (TNF-α), interferon (IFN)-ß, and interleukin (IL)-10 upon an FIPV infection in Crandell-Reese feline kidney (CRFK) cells and feline monocytes. METHODS: CRFK cells and monocytes from feline coronavirus (FCoV)-seronegative cats and FCoV-seropositive cats were infected with type II FIPV-79-1146. At four, 12, and 24 hours post-infection (hpi), the expression of TLR3, TLR7, TLR9, TNF-α, IFN-ß, and IL-10, and the viral load were measured using reverse transcription quantitative polymerase chain reaction. Viral protein production was confirmed using immunofluorescence. RESULTS: FIPV-infected CRFK showed the upregulation of TLR9, TNF-α, and IFN-ß expression between 4 and 24 hpi. Uninfected monocytes from FCoV-seropositive cats showed lower TLR3 and TLR9 expression but higher TLR7 expression compared to uninfected monocytes from FCoV-seronegative cats. FIPV-infected monocytes from FCoV-seropositive cats downregulated TLR7 and TNF-α expression between 4 and 24 hpi, and 4 and 12 hpi, respectively. IFN-ß was upregulated early in FIPV-infected monocytes from FCoV-seropositive cats, with a significant difference observed at 12 hpi compared to FCoV-seronegative cats. The viral load in the CRFK and FIPV-infected monocytes in both cohorts of cats was similar over time. CONCLUSION: TLR7 may be the key TLR involved in evading the innate response against inhibiting TNF-α production. Distinct TLR expression profiles between FCoV-seronegative and FCoV-seropositive cats were observed. The associated TLR that plays a role in the induction of IFN-ß needs to be explored further.


Subject(s)
Cat Diseases , Coronavirus, Feline , Feline Infectious Peritonitis , Animals , Cats , Coronavirus, Feline/genetics , Coronavirus, Feline/metabolism , Cytokines/genetics , Cytokines/metabolism , Kidney/metabolism , Monocytes/metabolism , Toll-Like Receptor 3
17.
Viruses ; 14(4)2022 04 01.
Article in English | MEDLINE | ID: covidwho-1776355

ABSTRACT

Feline infectious peritonitis (FIP) is a systemic immune-mediated inflammatory perivasculitis that occurs in a minority of cats infected with feline coronavirus (FCoV). Various therapies have been employed to treat this condition, which was previously usually fatal, though no parameters for differentiating FIP recovery from remission have been defined to enable clinicians to decide when it is safe to discontinue treatment. This retrospective observational study shows that a consistent reduction of the acute phase protein alpha-1 acid glycoprotein (AGP) to within normal limits (WNL, i.e., 500 µg/mL or below), as opposed to duration of survival, distinguishes recovery from remission. Forty-two cats were diagnosed with FIP: 75% (12/16) of effusive and 54% (14/26) of non-effusive FIP cases recovered. Presenting with the effusive or non-effusive form did not affect whether or not a cat fully recovered (p = 0.2). AGP consistently reduced to WNL in 26 recovered cats but remained elevated in 16 cats in remission, dipping to normal once in two of the latter. Anaemia was present in 77% (23/30) of the cats and resolved more quickly than AGP in six recovered cats. The presence of anaemia did not affect the cat's chances of recovery (p = 0.1). Lymphopenia was observed in 43% (16/37) of the cats and reversed in nine recovered cats but did not reverse in seven lymphopenic cats in the remission group. Fewer recovered cats (9/24: 37%) than remission cats (7/13: 54%) were lymphopenic, but the difference was not statistically different (p = 0.5). Hyperglobulinaemia was slower than AGP to return to WNL in the recovered cats. FCoV antibody titre was high in all 42 cats at the outset. It decreased significantly in 7 recovered cats but too slowly to be a useful parameter to determine discontinuation of antiviral treatments. Conclusion: a sustained return to normal levels of AGP was the most rapid and consistent indicator for differentiating recovery from remission following treatment for FIP. This study provides a useful model for differentiating recovery from chronic coronavirus disease using acute phase protein monitoring.


Subject(s)
Coronavirus Infections , Coronavirus, Feline , Feline Infectious Peritonitis , Orosomucoid , Acute-Phase Proteins , Animals , Cats , Coronavirus Infections/veterinary , Feline Infectious Peritonitis/diagnosis , Feline Infectious Peritonitis/therapy , Orosomucoid/metabolism
18.
J Virol ; 96(8): e0025022, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1769824

ABSTRACT

In late 2019, a novel coronavirus began circulating within humans in central China. It was designated SARS-CoV-2 because of its genetic similarities to the 2003 SARS coronavirus (SARS-CoV). Now that SARS-CoV-2 has spread worldwide, there is a risk of it establishing new animal reservoirs and recombination with native circulating coronaviruses. To screen local animal populations in the United States for exposure to SARS-like coronaviruses, we developed a serological assay using the receptor binding domain (RBD) from SARS-CoV-2. SARS-CoV-2's RBD is antigenically distinct from common human and animal coronaviruses, allowing us to identify animals previously infected with SARS-CoV or SARS-CoV-2. Using an indirect enzyme-linked immunosorbent assay (ELISA) for SARS-CoV-2's RBD, we screened serum from wild and domestic animals for the presence of antibodies against SARS-CoV-2's RBD. Surprisingly prepandemic feline serum samples submitted to the University of Tennessee Veterinary Hospital were ∼50% positive for anti-SARS RBD antibodies. Some of these samples were serologically negative for feline coronavirus (FCoV), raising the question of the etiological agent generating anti-SARS-CoV-2 RBD cross-reactivity. We also identified several white-tailed deer from South Carolina with anti-SARS-CoV-2 antibodies. These results are intriguing, as cross-reactive antibodies toward SARS-CoV-2 RBD have not been reported to date. The etiological agent responsible for seropositivity was not readily apparent, but finding seropositive cats prior to the current SARS-CoV-2 pandemic highlights our lack of information about circulating coronaviruses in other species. IMPORTANCE We report cross-reactive antibodies from prepandemic cats and postpandemic South Carolina white-tailed deer that are specific for that SARS-CoV RBD. There are several potential explanations for this cross-reactivity, each with important implications to coronavirus disease surveillance. Perhaps the most intriguing possibility is the existence and transmission of an etiological agent (such as another coronavirus) with similarity to SARS-CoV-2's RBD region. However, we lack conclusive evidence of prepandemic transmission of a SARS-like virus. Our findings provide impetus for the adoption of a One Health Initiative focusing on infectious disease surveillance of multiple animal species to predict the next zoonotic transmission to humans and future pandemics.


Subject(s)
Antibodies, Viral , Cats , Deer , Spike Glycoprotein, Coronavirus , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/veterinary , Cats/virology , Cross Reactions/immunology , Deer/virology , SARS Virus/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Viral Zoonoses/diagnosis , Viral Zoonoses/virology
19.
Vet Microbiol ; 268: 109395, 2022 May.
Article in English | MEDLINE | ID: covidwho-1735038

ABSTRACT

SARS-CoV-2 has exhibited varying pathogenesis in a variety of Mammalia family's including Canidae, Mustelidae, Hominidae, Cervidae, Hyaenidae, and Felidae. Novel SARS-CoV-2 variants characterized by spike protein mutations have recently resulted in clinical and epidemiological concerns, as they potentially have increased infectious rates, increased transmission, or reduced neutralization by antibodies produced via vaccination. Many variants have been identified at this time, but the variant of continuing concern has been the Delta variant (B.1.617.2), due to its increased transmissibility and infectious rate. Felines vaccinated using an experimental SARS-CoV-2 spike protein-based veterinary vaccine mounted a robust immune response to the SARS-CoV-2 spike protein. Using a reporter virus particle system and feline serum, we have verified that vaccinated felines produce antibodies that neutralize the SARS-CoV-2 Wuhan strain and variant B.1.617.2 at comparable levels.


Subject(s)
COVID-19 , Cat Diseases , Felidae , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19/veterinary , COVID-19 Vaccines , Cats , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
20.
Viruses ; 12(5)2020 05 24.
Article in English | MEDLINE | ID: covidwho-1726014

ABSTRACT

Feline infectious peritonitis (FIP) is a viral disease with a high morbidity and mortality by the FIP virus (FIPV, virulent feline coronavirus). Several antiviral drugs for FIP have been identified, but many of these are expensive and not available in veterinary medicine. Hydroxychloroquine (HCQ) is a drug approved by several countries to treat malaria and immune-mediated diseases in humans, and its antiviral effects on other viral infections (e.g., SARS-CoV-2, dengue virus) have been confirmed. We investigated whether HCQ in association with interferon-ω (IFN-ω) is effective for FIPV in vitro. A total of 100 µM of HCQ significantly inhibited the replication of types I and II FIPV. Interestingly, the combination of 100 µM of HCQ and 104 U/mL of recombinant feline IFN-ω (rfIFN-ω, veterinary registered drug) increased its antiviral activity against type I FIPV infection. Our study suggested that HCQ and rfIFN-ω are applicable for treatment of FIP. Further clinical studies are needed to verify the combination of HCQ and rIFN-ω will be effective and safe treatment for cats with FIP.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus, Feline/drug effects , Hydroxychloroquine/pharmacology , Interferon Type I/pharmacology , Analysis of Variance , Animals , Antiviral Agents/therapeutic use , Antiviral Agents/toxicity , Cats , Cell Line/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Coronavirus, Feline/pathogenicity , Drug Combinations , Feline Infectious Peritonitis/drug therapy , Feline Infectious Peritonitis/virology , Fluorescent Antibody Technique/veterinary , Hydroxychloroquine/therapeutic use , Hydroxychloroquine/toxicity , Interferon Type I/therapeutic use , Interferon Type I/toxicity , Virulence
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