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Viruses Aug 2023Feline coronavirus (FCoV) is a ubiquitous RNA virus of cats, which is transmitted faeco-orally. In these guidelines, the European Advisory Board on Cat Diseases (ABCD)... (Review)
Review
Feline coronavirus (FCoV) is a ubiquitous RNA virus of cats, which is transmitted faeco-orally. In these guidelines, the European Advisory Board on Cat Diseases (ABCD) presents a comprehensive review of feline infectious peritonitis (FIP). FCoV is primarily an enteric virus and most infections do not cause clinical signs, or result in only enteritis, but a small proportion of FCoV-infected cats develop FIP. The pathology in FIP comprises a perivascular phlebitis that can affect any organ. Cats under two years old are most frequently affected by FIP. Most cats present with fever, anorexia, and weight loss; many have effusions, and some have ocular and/or neurological signs. Making a diagnosis is complex and ABCD FIP Diagnostic Approach Tools are available to aid veterinarians. Sampling an effusion, when present, for cytology, biochemistry, and FCoV RNA or FCoV antigen detection is very useful diagnostically. In the absence of an effusion, fine-needle aspirates from affected organs for cytology and FCoV RNA or FCoV antigen detection are helpful. Definitive diagnosis usually requires histopathology with FCoV antigen detection. Antiviral treatments now enable recovery in many cases from this previously fatal disease; nucleoside analogues (e.g., oral GS-441524) are very effective, although they are not available in all countries.
Topics: Cats; Animals; Feline Infectious Peritonitis; Body Fluids; Antigens, Viral; Antiviral Agents; Coronavirus, Feline
PubMed: 37766254
DOI: 10.3390/v15091847 -
Journal of Veterinary Internal Medicine 2023Feline infectious peritonitis (FIP) is a viral disease in cats, caused by certain strains of coronavirus and has a high case fatality rate. (Observational Study)
Observational Study
BACKGROUND
Feline infectious peritonitis (FIP) is a viral disease in cats, caused by certain strains of coronavirus and has a high case fatality rate.
OBJECTIVE
This case series reports the outcomes of treatment of cats with FIP using molnupiravir.
ANIMALS
Eighteen cats diagnosed with FIP at the You-Me Animal Clinic, Sakura-shi, Japan between January and August 2022, and whose owners gave informed consent to this experimental treatment.
METHODS
For this prospective observational study, molnupiravir tablets were compounded in-house at the You-Me Animal Clinic. Owners administered 10-20 mg/kg PO twice daily. Standard treatment duration was 84 days.
RESULTS
Among 18 cats, 13 cats had effusive FIP and 5 had noneffusive FIP. Three cats had neurological or ocular signs of FIP before treatment. Four cats, all with effusive FIP, died or were euthanized within 7 days of starting treatment. The remaining 14 cats completed treatment and remained in remission at the time of writing (139-206 days after starting treatment). Elevated serum alanine transaminase (ALT) activity was found in 3 cats, all at Days 7-9, and all recovered without management. Two cats with jaundice were hospitalized, 1 during treatment (Day 37) and 1 with severe anemia at the start of treatment.
CONCLUSIONS AND CLINICAL IMPORTANCE
This case series suggests that molnupiravir might be an effective and safe treatment for domestic cats with FIP at a dose of 10-20 mg/kg twice daily.
Topics: Cats; Animals; Feline Infectious Peritonitis; Coronavirus, Feline; Coronavirus Infections; Virus Diseases; Cat Diseases
PubMed: 37551843
DOI: 10.1111/jvim.16832 -
Theranostics 2023Sepsis is a potentially life-threatening condition caused by the body's response to a severe infection. Although the identification of multiple pathways involved in...
Sepsis is a potentially life-threatening condition caused by the body's response to a severe infection. Although the identification of multiple pathways involved in inflammation, tissue damage and aberrant healing during sepsis, there remain unmet needs for the development of new therapeutic strategies essential to prevent the reoccurrence of infection and organ injuries. Expression of Suppressor of Fused (Sufu) was evaluated by qRT-PCR, western blotting, and immunofluorescence in murine lung and peritoneal macrophages. The significance of Sufu expression in prognosis was assessed by Kaplan-Meier survival analysis. The GFP-TRAF6-expressing stable cell line (GFP-TRAF6 Blue cells) were constructed to evaluate phase separation of TRAF6. Phase separation of TRAF6 and the roles of Sufu in repressing TRAF6 droplet aggregation were analyzed by co-immunoprecipitation, immunofluorescence, Native-PAGE, FRAP and assays using purified proteins. The effects of Sufu on sepsis-induced lung inflammation were evaluated by cell function assays, LPS-induced septic shock model and polymicrobial sepsis-CLP mice model. We found that Sufu expression is reduced in early response to lipopolysaccharide (LPS)-induced acute inflammation in murine lung and peritoneal macrophages. Deletion of Sufu aggravated LPS-induced and CLP (cecal ligation puncture)-induced lung injury and lethality in mice, and augmented LPS-induced proinflammatory gene expression in cultured macrophages. In addition, we identified the role of Sufu as a negative regulator of the Toll-Like Receptor (TLR)-triggered inflammatory response. We further demonstrated that Sufu directly interacts with TRAF6, thereby preventing oligomerization and autoubiquitination of TRAF6. Importantly, TRAF6 underwent phase separation during LPS-induced inflammation, which is essential for subsequent ubiquitination activation and NF-κB activity. Sufu inhibits the phase-separated TRAF6 droplet formation, preventing NF-κB activation upon LPS stimulation. In a septic shock model, TRAF6 depletion rescued the augmented inflammatory phenotype in mice with myeloid cell-specific deletion of Sufu. These findings implicated Sufu as an important inhibitor of TRAF6 in sepsis and suggest that therapeutics targeting Sufu-TRAF6 may greatly benefit the treatment of sepsis.
Topics: Mice; Animals; NF-kappa B; TNF Receptor-Associated Factor 6; Shock, Septic; Lipopolysaccharides; Inflammation; Pneumonia; Sepsis
PubMed: 37441604
DOI: 10.7150/thno.83676