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

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 Academic Editors: Subir Sarker and Qibin Geng Received: 2 December 2024 Revised: 1 February 2025 Accepted: 3 February 2025 Published: 6 February 2025 Citation: Del Sorbo, L.; Giugliano, R.; Cerracchio, C.; Iovane, V.; Salvatore, M.M.; Serra, F.; Amoroso, M.G.; Pellegrini, F.; Levante, M.; Capozza, P.; et al. In Vitro Evaluation of Aryl Hydrocarbon Receptor Involvement in Feline Coronavirus Infection. Viruses 2025, 17, 227. https://doi.org/10.3390/ v17020227 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/). development of feline infectious peritonitis (FIP). In this context, to restrain the impact of FCoVinfection, 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 infec tion in Crandell Feline Kidney (CRFK) and in canine fibrosarcoma (A72) cells. Following infection with feline enteric CoV (FECV), strain “München”, a significant activation of AhRandofits target CYP1A1, was observed. The selective AhR antagonist CH223191 pro voked 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 CRFKcells was detected, outlining their involvement in antiviral activity.