Modulation of the Aryl Hydrocarbon Receptor Signaling Pathway Impacts on Junín Virus Replication

MIGUEL ANGEL PELÁEZ; MARIA FLORENCIA TORTI; ALVAREZ DE LAURO AARON; AGOSTINA BELEN MARQUEZ; FEDERICO GIOVANNONI; ELSA BEATRIZ DAMONTE; CYBELE GARCIA

viruses

MDPI Open Access Journals

Año: 2023

Junín virus (JUNV), a member of the family Arenaviridae, is the etiological agent of theArgentine hemorrhagic fever, an endemic disease in the rural region of Argentina lacking a specificchemotherapy. Aryl hydrocarbon receptor (AHR) is expressed in several mammalian tissues andhas been indicated as a sensor of ligands from variable sources and a modulator of the cell immuneresponse. Interestingly, recent studies have suggested that the activation or depression of the AHRsignaling pathway may play a role in the outcome of diverse human viral infections. In the presentreport, the effect of the pharmacological modulation of AHR on JUNV in vitro infection was analyzed.An initial microarray screening showed that the AHR pathway was overexpressed in JUNV-infectedhepatic cells. Concomitantly, the infection of Vero and Huh-7 cells with the JUNV strains IV4454 andCandid#1 was significantly inhibited in a dose-dependent manner by treatment with CH223191, aspecific AHR antagonist, as detected by infectivity assays, real-time RT-PCR and immunofluorescencedetection of viral proteins. Furthermore, the pro-viral role of AHR in JUNV infection appears tobe independent of the IFN-I pathway. Our findings support the promising perspectives of thepharmacological modulation of AHR as a potential target for the control of AHF.