Journal Article

In Vitro Evaluation of Aryl Hydrocarbon Receptor Involvement in Feline Coronavirus Infection

Galdiero, Massimiliano, Andolfi, Anna, Pellegrini, Francesco, Levante, Martina, Capozza, Paolo, Amoroso, Maria Grazia, Salvatore, Maria Michela, Serra, Francesco, Del Sorbo, Luca, Fusco, Giovanna, Pratelli, Annamaria, Giugliano, Rosa, Cerracchio, Claudia, Diakoudi, Georgia, Iovane, Valentina, Fiorito, Filomena

2025

Overview

Feline coronavirus (FCoV) is an alphacoronavirus (αCoV) that causes moderate or chronic asymptomatic infection in cats. However, in a single infected cat, FCoV can modify its cellular tropism by acquiring the ability to infect macrophages, resulting in the development of feline infectious peritonitis (FIP). In this context, to restrain the impact of FCoV infection, scientific research has focused attention on the development of antiviral therapies involving novel mechanisms of action. Recent studies have demonstrated that aryl hydrocarbon receptor (AhR) signaling regulates the host response to different human and animal CoVs. Hence, the mechanism of action of AhR was evaluated upon FCoV infection in Crandell Feline Kidney (CRFK) and in canine fibrosarcoma (A72) cells. Following infection with feline enteric CoV (FECV), strain “München”, a significant activation of AhR and of its target CYP1A1, was observed. The selective AhR antagonist CH223191 provoked a reduction in FCoV replication and in the levels of viral nucleocapsid protein (NP). Furthermore, the effect of the AhR inhibitor on the acidity of lysosomes in infected cells was observed. Our findings indicate that FCoV acts on viral replication that upregulates AhR. CH223191 repressed virus yield through the inhibition of AhR. In this respect, for counteracting FCoV, AhR represents a new target useful for identifying antiviral drugs. Moreover, in the presence of CH223191, the alkalinization of lysosomes in FCoV-infected CRFK cells was detected, outlining their involvement in antiviral activity.

• Publisher: MDPI AG,MDPI
• Subject: Acidity / AhR signaling / Animals / Antiviral activity / Antiviral agents / Antiviral Agents - pharmacology / Antiviral drugs / Asymptomatic infection / Cats / Cell growth / Cell Line / CH223191 / Chronic infection / Coronavirus, Feline - drug effects / Coronavirus, Feline - physiology / Coronaviruses / Cytochrome P-450 CYP1A1 - metabolism / Cytochrome P450 / Dioxins / Disease transmission / Dogs / Enzymes / Evolution & development / FCoV / Feline infectious peritonitis / Feline Infectious Peritonitis - metabolism / Feline Infectious Peritonitis - virology / Fibrosarcoma / Hydrocarbons / in vitro system / Infections / Ligands / Lysosomes / Macrophages / Morphology / Mutation / Nucleocapsids / Peritonitis / Receptors, Aryl Hydrocarbon - antagonists & inhibitors / Receptors, Aryl Hydrocarbon - genetics / Receptors, Aryl Hydrocarbon - metabolism / Replication / Respiratory diseases / Severe acute respiratory syndrome coronavirus 2 / Tropism / Virus Replication - drug effects / Viruses