IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
AHR IS A FLAVIVIRUS HOST FACTOR AND A TARGET FOR ANTIVIRAL THERAPY
Autor/es:
FEDERICO GIOVANNONI; FRANCISCO QUINTANA; MARIA FLORENCIA TORTI; IRENE BOSCH; CYBELE GARCIA
Lugar:
Minneapolis
Reunión:
Congreso; American Society for Virology 2019; 2019
Institución organizadora:
American Society for Viorlogy (ASV)
Resumen:
Dengue (DENV) and Zika (ZIKV) are emergent flaviviruses that haveraised global concern due to its association with disease. No therapyis yet available to limit flaviviruses infection, thus, the identificationof host factors involved in their replication is crucial for thedevelopment of new therapeutics. In genome-wide transcriptionalstudies we found that DENV and ZIKV infection activate the arylhydrocarbon receptor (AHR). AHR activation by ZIKV limits theproduction of type I interferons involved in innate immunity.Moreover, ZIKV-triggered AHR activation suppresses intrinsicimmunity driven by the promyelocytic leukemia protein (PML),which we defined as a factor limiting ZIKV replication. Collectively,these findings identify AHR as a target to suppress ZIKV replication.Indeed, AHR inhibition in vitro suppressed the replication of ZIKVstrains from Uganda, Puerto Rico, and Argentina. In additionalexperiments, AHR inhibition also suppressed the replication ofall four DENV serotypes. In summary, we identified AHR as a hostfactor for flavivirus replication and PML as a driver of anti-flavivirusintrinsic immunity. Additionaly, these studies identify AHR as apotential target for developing an effective antiviral therapy againstDENV and ZIKV.