RIG-I mediates an antiviral response to Crimean-Congo hemorrhagic fever virus.

Spengler JR1, Patel JR2, Chakrabarti AK1, Zivcec M1, García-Sastre A3, Spiropoulou CF1, Bergeron É4.

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Abstract

In the cytoplasm, the retinoic acid-inducible gene I (RIG-I) senses the RNA genomes of several RNA viruses. RIG-I binds to viral RNA, eliciting an antiviral response via the cellular adaptor MAVS. Crimean-Congo hemorrhagic fever virus (CCHFV), a negative sense RNA virus with a 5' -monophosphorylated genome, is a highly pathogenic zoonotic agent with significant public health and clinical implications. We found that, during CCHFV infection, RIG-I mediated a type-I interferon (IFN) response via MAVS. Interfering with RIG-I signaling reduced IFN production and IFN-stimulated gene expression, and increased viral replication. Immunostimulatory RNA was isolated from CCHFV-infected cells and from virion preparations, and RIG-I co-immunoprecipitation of infected cell lysates isolated immunostimulatory CCHFV RNA. This report serves as the first description of a pattern recognition receptor for CCHFV and highlights a critical signaling pathway in the antiviral response to CCHFV.

IMPORTANCE:

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus with significant public health and clinical impact. In order for cells to respond to virus infection, they must recognize the virus as foreign and initiate antiviral signaling. To date, the receptors involved in recognition of CCHFV are not known. Herein we investigate and identify retinoic acid-inducible gene I (RIG-I) as a receptor involved in initiating an antiviral response to CCHFV. This receptor was initially not expected to play a role in CCHFV recognition because of characteristics of the viral genome. These findings are important in understanding the antiviral response to CCHFV and support continued investigation into the spectrum of potential viruses recognized by RIG-I.