Characterization of peritoneal cells from cats with experimentally-induced feline infectious peritonitis (FIP) using RNA-seq

Watanabe, Rie; Eckstrand, Chrissy; Liu, Hongwei; Pedersen, Niels C

doi:10.1186/s13567-018-0578-y

Cited by 20 publications

(25 citation statements)

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“…Pro-inflammatory cytokines and antiviral-related genes such as MX1, viperin and IFNγ have also been observed in tissues harvested from FCoV-infected cats with FIP [46]. In addition, recent reports focused on gene expression profiles from mesenteric or peritoneal macrophages harvested from cats with FIP revealed expression of pattern recognition receptors including toll, NOD and RIG-like receptors, pro-apoptotic genes, and genes related to differentiation of M1 macrophages in contrast to reduced expression of MCH class II receptor genes [47,48]. Lastly, the role of host anti-inflammatory factors such as regulatory T cells and IL-10 as well as innate factors such as natural killer cells factors warrant further examination based on other recent reports [29,49].…”

Section: Discussionmentioning

confidence: 99%

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Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

et al. 2019

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Background Feline infectious peritonitis (FIP) is considered highly fatal in its naturally occurring form, although up to 36% of cats resist disease after experimental infection, suggesting that cats in nature may also resist development of FIP in the face of infection with FIP virus (FIPV). Previous experimental FIPV infection studies suggested a role for cell-mediated immunity in resistance to development of FIP. This experimental FIPV infection study in specific pathogen free (SPF) kittens describes longitudinal antiviral T cell responses and clinical outcomes ranging from rapid progression, slow progression, and resistance to disease. Results Differences in disease outcome provided an opportunity to investigate the role of T cell immunity to FIP determined by T cell subset proliferation after stimulation with different viral antigens. Reduced total white blood cell (WBC), lymphocyte and T cell counts in blood were observed during primary acute infection for all experimental groups including cats that survived without clinical FIP. Antiviral T cell responses during early primary infection were also similar between cats that developed FIP and cats remaining healthy. Recovery of antiviral T cell responses during the later phase of acute infection was observed in a subset of cats that survived longer or resisted disease compared to cats showing rapid disease progression. More robust T cell responses at terminal time points were observed in lymph nodes compared to blood in cats that developed FIP. Cats that survived primary infection were challenged a second time to pathogenic FIPV and tested for antiviral T cell responses over a four week period. Nine of ten rechallenged cats did not develop FIP or T cell depletion and all cats demonstrated antiviral T cell responses at multiple time points after rechallenge. Conclusions In summary, definitive adaptive T cell responses predictive of disease outcome were not detected during the early phase of primary FIPV infection. However emergence of antiviral T cell responses after a second exposure to FIPV, implicated cellular immunity in the control of FIPV infection and disease progression. Virus host interactions during very early stages of FIPV infection warrant further investigation to elucidate host resistance to FIP.

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Section: Discussionmentioning

confidence: 99%

“…5A). However, CD4 and CD8 T cell responses of the highest magnitude (> 1% proliferating T cells) were observed for MLN (9,29,30,45,48,49, and 50 day PI) and blood (15 days PI) when tested against either WKV or viral peptides (Fig. 5A).…”

Section: Virus-specific T Cell Proliferation Responses In Blood and Lmentioning

confidence: 98%

Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

et al. 2019

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“…The identification of effective antiviral strategies for treating FIPV-infected cats holds translational implications for the ongoing SARS-CoV-2 pandemic. FIPV-infection in cats is reminiscent of coronavirus infection in ferrets [61,62] and has been compared to the pathogenesis of other chronic, macrophage-dependent diseases such as tuberculosis [63]. As the clinical and pathogenic details of SARS-CoV-2 infection in people continues to emerge, there appears to be some overlap with FIPV in anatomic distribution, clinical manifestation, and likely, response to certain antiviral therapies.…”

Section: Discussionmentioning

confidence: 99%

“…The cellular receptor for the less clinically relevant FIPV serotype II has been identified as feline aminopeptidase peptidase (fAPN) [4]. A study utilizing RNAseq to evaluate gene expression profiles of ascites cells obtained from cats with FIP did not identify expression of ACE2, suggesting that ACE2 is unlikely to be the serotype I FIPV receptor [63]. More investigation into the identity of the serotype I FIPV receptor is warranted.…”

Section: Discussionmentioning

confidence: 99%

A rational approach to identifying effective combined anticoronaviral therapies against feline coronavirus

Cook

Vogel

Castillo

et al. 2020

Preprint

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AbstractFeline infectious peritonitis (FIP), caused by a genetic mutant of feline enteric coronavirus known as FIPV, is a highly fatal disease of cats with no currently available vaccine or FDA-approved cure. Dissemination of FIPV in affected cats results in a range of clinical signs including cavitary effusions, anorexia, fever and lesions of pyogranulomatous vasculitis and peri-vasculitis with or without central nervous system and/or ocular involvement. There is a critical need for effective and approved antiviral therapies against coronaviruses including FIPV and zoonotic coronaviruses such as SARS-CoV-2, the cause of COVID-19. With regards to SARS-CoV-2, preliminary evidence suggests that there may be potential clinical and pathological overlap with feline coronaviral disease including enteric and neurological involvement in some cases. We have screened 89 putative antiviral compounds and have identified 25 compounds with antiviral activity against FIPV, representing a variety of drug classes and mechanisms of antiviral action. Based upon successful combination treatment strategies for human patients with HIV or hepatitis C virus infections, we have identified combinations of drugs targeting different steps of the FIPV life cycle resulting in synergistic antiviral effect. Translationally, we suggest that a combined anticoronaviral therapy (cACT) with multiple mechanisms of action and penetration of all potential anatomic sites of viral infection should be applied towards other challenging to treat coronaviruses, like SARS-CoV-2.Author summaryWe have screened 89 compounds in vitro for antiviral activity against FIPV. The putative antiviral activity of these compounds was either purported to be a direct effect on viral proteins involved in viral replication or an indirect inhibitory effect on normal cellular pathways usurped by FIPV to aid viral replication. Twenty-five of these compounds were found to have significant antiviral activity. Certain combinations of these compounds were determined to be superior to monotherapy alone.

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“…In domestic cats, TLR4 polymorphisms are yet to be investigated although cats suffer many of the infectious and inflammatory conditions that are linked to altered TLR4 expression in humans. Feline TLR4 has been associated with infectious disease pathogenesis in cats; expression of TLR4 is increased in neutrophil exposure to Microsporum canis, and in feline infectious peritonitis (FIP) (Cambier et al, 2016;Watanabe et al, 2018) while progesterone-induced TLR4 down-regulation is implicated in the development of pyometra in breeding queens (Jursza et al, 2015). Feline breed-specific differences in susceptibility to viral and fungal infections, including FIP and invasive mycoses, are documented (Pesteanu-Somogyi et al, 2006;Worthing et al, 2012;Barrs et al, 2015), but potential underlying immune dysfunction remains under-investigated.…”

Section: Introductionmentioning

confidence: 99%

Breed-specific variations in the coding region of toll-like receptor 4 in the domestic cat

Whitney

Haase

Beatty

et al. 2019

Veterinary Immunology and Immunopathology

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cluding sepsis, aspergillosis and inflammatory bowel disease. Some of these TLR4 polymorphisms are racially specific. We hypothesised that feline TLR4 polymorphisms might underlie an observed increased risk to infectious and inflammatory diseases in some cat breeds. The aim of this study was to identify breed-specific variations in the coding region of feline TLR4 and to model the effect of mutations on protein structure and function in silico. The entire coding region of TLR4 was sequenced in 8 groups (7 pure-bred, 1 crossbred) of domestic cats (Felis catus) comprising 158 individuals. Twenty-two single nucleotide polymorphisms (SNPs) were identified in TLR4, with 16 located in the coding region (11 non-synonymous) and four in the 3′UTR. Comparison of breed specific allelic frequencies indicated that Burmese and British shorthairs most commonly differed from other breeds. In silico analyses to predict the impact of the 11 non-synonymous variants indicated a deleterious effect on protein structure for one SNP (c.869 G > A), which was not associated with a specific breed. Overall, findings from this study do not support a role of TLR4 dysfunction in breed-predispositions to infectious diseases in domestic cats in Australia.

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Characterization of peritoneal cells from cats with experimentally-induced feline infectious peritonitis (FIP) using RNA-seq

Cited by 20 publications

References 67 publications

Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

A rational approach to identifying effective combined anticoronaviral therapies against feline coronavirus

Breed-specific variations in the coding region of toll-like receptor 4 in the domestic cat

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