Physical interaction between bovine viral diarrhea virus nonstructural protein 4A and adenosine deaminase acting on RNA (ADAR)
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Bovine viral diarrhea virus (BVDV) is a positive-sense RNA virus known to produce double-stranded RNA (dsRNA) during its replication in the cytoplasm. Extended dsRNA duplexes can be hyperedited by adenosine deaminase acting on RNA (ADAR), which catalyzes adenosine (A)-to-inosine (I) editing. A-to-I editing has been reported for various viruses. A number of cellular antiviral defense strategies are stimulated by dsRNA, and this may involve hyperediting of dsRNA by ADARs, followed by targeted cleavage by cytoplasmic endonucleases. Here, we identify ADAR as a binding partner of BVDV NS4A in vitro and in vivo and show that the N-terminal domain of NS4A is the ADAR-binding domain. We also show that ADAR has an inhibitory effect on BVDV replication when overexpressed in BVDV-infected bovine cells. Our findings suggest a role of NS4A in the interaction of BVDV with ADAR that favors virus replication.
KeywordsBovine Viral Diarrhea Virus Bovine Viral Diarrhea Virus Infection Subgenomic Replicon Bovine Viral Diarrhea Virus Strain NS4A Sequence
We thank Dr. Till Rümenapf and Dr. Graeme Conn for providing research materials. This work was supported in part by a Research and Development Project for Application in Promoting New Policies in Agriculture, Forestry and Fisheries grant from the Ministry of Agriculture, Forestry and Fisheries, and by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan.