An update on feline infectious peritonitis: Diagnostics and therapeutics

Pedersen, Niels C

doi:10.1016/j.tvjl.2014.04.016

Cited by 167 publications

(291 citation statements)

References 69 publications

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“…3.5. Concentrations of GS-441524 in aqueous humor and CSF were onefifth that of plasma FIP is well known to involve both the eyes and CNS (Pedersen, 2014b) and it is therefore important to know how well GS-441524 penetrates the blood/brain and blood/eye barriers. Two young adult cats were given 10 mg/kg of GS-441524 SC and two cats were untreated to provide control fluids.…”

Section: Effective Intracellular Levels Of Non-phosphorylated and Phomentioning

confidence: 99%

“…Feline infectious peritonitis (FIP) is a well-documented infectious disease of cats, especially kittens, adolescents and young adults from shelters, kitten foster/rescues and catteries (Pedersen, 2014b). The causative FIP virus (FIPV) is a positive single stranded RNA virus belonging to the family Coronaviridae, species Alphacoronavirus 1, subspecies feline coronavirus, biotype FIP virus (FIPV) (Tekes and Thiel, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…FIPV infection has a complex immunopathogenesis, a feature shared by other coronavirus infections (de Wilde et al, 2017), and has become one of the most researched infectious diseases of cats since its discovery over a half century ago (Kipar and Meli, 2014;Pedersen, 2014aPedersen, , 2014bTekes and Thiel, 2016). Despite these advances, modern treatment options for FIP remain palliative and vaccines have proven either unsafe or ineffective (Pedersen, 2014b). The emergence of SARS-associated coronavirus has provided an impetus for an investment in antiviral discovery focused on coronaviruses (De Clercq, 2004).…”

Section: Introductionmentioning

confidence: 99%

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The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

Murphy

Perron

Murakami

et al. 2018

Veterinary Microbiology

150

219

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Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats. Recent studies of diseases caused by several RNA viruses in people and other species indicate that antiviral therapy may be effective against FIP in cats. The small molecule nucleoside analog GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. We determined that GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. We determined the pharmacokinetics of GS-441524 in cats in vivo and established a dosage that would sustain effective blood levels for 24 h. In an experimental FIPV infection of cats, GS-441524 treatment caused a rapid reversal of disease signs and return to normality with as little as two weeks of treatment in 10/10 cats and with no apparent toxicity.

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Section: Effective Intracellular Levels Of Non-phosphorylated and Phomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

Murphy

Perron

Murakami

et al. 2018

Veterinary Microbiology

150

219

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“…Lymphopenia is a consistent feature of both naturally (Pedersen, 2009(Pedersen, , 2014b and experimentally induced-FIP (Dean et al, 2003;de Groot-Mijnes et al, 2005). The role of lymphopenia in FIP has not been determined, but it has been equated with a decrease in cellular immunity and ultimate disease outcome in experimental infections (de Groot-Mijnes et al, 2005;Vermeulen et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…The emphasis of FIP diagnostics has long been on developing a simple blood test that would reliably and specifically detect the causative virus (Pedersen, 2014b). Herrewegh et al (1995) reported on the detection of viral RNA in blood serum or plasma of cats experimentally and naturally infected with FIPV using a nested RT-PCR that amplified a sequence within the 3 0 -UTR that was highly conserved among 10 different FIPV and FECV isolates.…”

Section: Introductionmentioning

confidence: 99%

Levels of feline infectious peritonitis virus in blood, effusions, and various tissues and the role of lymphopenia in disease outcome following experimental infection

Pedersen

Eckstrand

Liu

et al. 2015

Veterinary Microbiology

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Twenty specific pathogen free cats were experimentally infected with a virulent cat-passaged type I field strain of FIPV. Eighteen cats succumbed within 2-4 weeks to effusive abdominal FIP, one survived for 6 weeks, and one seroconverted without outward signs of disease. A profound drop in the absolute count of blood lymphocytes occurred around 2 weeks post-infection (p.i.) in cats with rapid disease, while the decrease was delayed in the one cat that survived for 6 weeks. The absolute lymphocyte count of the surviving cat remained within normal range. Serum antibodies as measured by indirect immunofluorescence appeared after 2 weeks p.i. and correlated with the onset of disease signs. Viral genomic RNA was either not detectable by reverse transcription quantitative real-time PCR (RT-qPCR) or detectable only at very low levels in terminal tissues not involved directly in the infection, including hepatic and renal parenchyma, cardiac muscle, lung or popliteal lymph node. High tissue virus loads were measured in severely affected tissues such as the omentum, mesenteric lymph nodes and spleen. High levels of viral genomic RNA were also detected in whole ascitic fluid, with the cellular fraction containing 10-1000 times more viral RNA than the supernatant. Replicating virus was strongly associated with macrophages by immunohistochemistry. Virus was usually detected at relatively low levels in feces and there was no evidence of enterocyte infection. Viral genomic RNA was not detected at the level of test sensitivity in whole blood, plasma, or the white cell fraction in terminal samples from the 19 cats that succumbed or in the single survivor. These studies reconfirmed the effect of lymphopenia on disease outcome. FIPV genomic RNA was also found to be highly macrophage associated within diseased tissues and effusions as determined by RT-qPCR and immunohistochemistry but was not present in blood.

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Urinary Disease

Hudson¹

2020

Feline Diagnostic Imaging

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An update on feline infectious peritonitis: Diagnostics and therapeutics

Cited by 167 publications

References 69 publications

The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

Levels of feline infectious peritonitis virus in blood, effusions, and various tissues and the role of lymphopenia in disease outcome following experimental infection

Urinary Disease

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