Dataset Information

Differential induction of type I interferon by type I and type II feline coronaviruses in vitro.

ABSTRACT: Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease in wild and domestic cats. There are two FCoV serotypes. Both type I and II FCoV can replicate in Felis catus whole fetus (fcwf)-4 cells, but the replicability of type I FCoV in feline cell lines is lower than that of type II FCoV, the reason for which is unclear. Inhibition of IFN? production by non-structural and structural proteins, excluding spike protein has been reported in many coronavirus infections. In this study, we investigated whether IFN? is involved in the difference in replicability in feline cell lines between types I and II FCoV. When fcwf-4 cells were infected with FCoV, the virus titer of type II FCoV in the culture supernatant was higher than that of type I FIPV. When the IFN? expression level in FCoV-infected fcwf-4 cells was semi-quantitatively analyzed, infection with type I FIPV, excluding type I FIPV UCD-1, highly induced IFN? expression. In contrast, induction of IFN? by type II FCoV infection was significantly lower than that by type I FIPV. In addition, when fcwf-4 cells were adsorbed by FIPV and then stimulated with Poly(I:C), type II FCoV infection inhibited Poly(I:C)-induced IFN? gene expression. Also, the proliferation of type I FIPV was enhanced by a IFN inhibitor. These findings clarified that, unlike type I FIPV, type II FCoV strongly inhibits IFN? expression in infected cells. It was also suggested that the IFN?-inducing ability is different among type I FIPV strains.

SUBMITTER: Doki T

PROVIDER: S-EPMC7111755 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential induction of type I interferon by type I and type II feline coronaviruses in vitro.

Doki Tomoyoshi T Yabe Midori M Takano Tomomi T Hohdatsu Tsutomu T

Research in veterinary science 20180921

Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease in wild and domestic cats. There are two FCoV serotypes. Both type I and II FCoV can replicate in Felis catus whole fetus (fcwf)-4 cells, but the replicability of type I FCoV in feline cell lines is lower than that of type II FCoV, the reason for which is unclear. Inhibition of IFNβ production by non-structural and structural proteins, excluding spike protein has been reported in many coronavirus infections. ...[more]

PMID: 30265871

Similar Datasets

Project description:UnlabelledFeline infectious peritonitis and virulent, systemic calicivirus infection are caused by certain types of feline coronaviruses (FCoVs) and feline caliciviruses (FCVs), respectively, and are important infectious diseases with high fatality rates in members of the Felidae family. While FCoV and FCV belong to two distinct virus families, the Coronaviridae and the Caliciviridae, respectively, they share a dependence on viral 3C-like protease (3CLpro) for their replication. Since 3CLpro is functionally and structurally conserved among these viruses and essential for viral replication, 3CLpro is considered a potential target for the design of antiviral drugs with broad-spectrum activities against these distinct and highly important viral infections. However, small-molecule inhibitors against the 3CLpro enzymes of FCoV and FCV have not been previously identified. In this study, derivatives of peptidyl compounds targeting 3CLpro were synthesized and evaluated for their activities against FCoV and FCV. The structures of compounds that showed potent dual antiviral activities with a wide margin of safety were identified and are discussed. Furthermore, the in vivo efficacy of 3CLpro inhibitors was evaluated using a mouse model of coronavirus infection. Intraperitoneal administration of two 3CLpro inhibitors in mice infected with murine hepatitis virus A59, a hepatotropic coronavirus, resulted in significant reductions in virus titers and pathological lesions in the liver compared to the findings for the controls. These results suggest that the series of 3CLpro inhibitors described here may have the potential to be further developed as therapeutic agents against these important viruses in domestic and wild cats. This study provides important insights into the structure and function relationships of 3CLpro for the design of antiviral drugs with broader antiviral activities.ImportanceFeline infectious peritonitis virus (FIPV) is the leading cause of death in young cats, and virulent, systemic feline calicivirus (vs-FCV) causes a highly fatal disease in cats for which no preventive or therapeutic measure is available. The genomes of these distinct viruses, which belong to different virus families, encode a structurally and functionally conserved 3C-like protease (3CLpro) which is a potential target for broad-spectrum antiviral drug development. However, no studies have previously reported a structural platform for the design of antiviral drugs with activities against these viruses or on the efficacy of 3CLpro inhibitors against coronavirus infection in experimental animals. In this study, we explored the structure-activity relationships of the derivatives of 3CLpro inhibitors and identified inhibitors with potent dual activities against these viruses. In addition, the efficacy of the 3CLpro inhibitors was demonstrated in mice infected with a murine coronavirus. Overall, our study provides the first insight into a structural platform for anti-FIPV and anti-FCV drug development.

Dataset Information

Differential induction of type I interferon by type I and type II feline coronaviruses in vitro.

Publications

Differential induction of type I interferon by type I and type II feline coronaviruses in vitro.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets