BVDV Npro protein mediates the BVDV induced immunosuppression through interaction with cellular S100A9 protein

• DOI: 10.1016/j.micpath.2018.05.047
• Publication Date: 2018-05-31T02:16:53Z
• Authors: Mahmoud F. Darweesh; Mrigendra K.S. Ra...; Lyle J. Braun; Jai S. Rohila; Christopher C.L. ...
• Keywords: Immunosuppression Therapy; 0301 basic medicine; Diarrhea Viruses, Bovine Viral; Cattle Diseases; Virus Replication; Article; Immunity, Innate; Cell Line; 3. Good health; Toll-Like Receptor 4; Viral Proteins; 03 medical and health sciences; Interferon Type I; Myeloid Differentiation Factor 88; Animals; Calgranulin B; Bovine Virus Diarrhea-Mucosal Disease; Cattle; RNA, Small Interfering

The innate immune response is a vital part of the body's antiviral defense system. The innate immune response is initiated by various receptor interactions, including danger associated molecular patterns (DAMPs). The S100A9 is a member of the DAMPs protein family and, is released by activated phagocytic cells such as neutrophils, monocytes, macrophages or endothelial cells, and S100A9 induces its effect through TLR4/MyD88 pathway. Bovine viral diarrhea virus (BVDV) is one of the major devastating disease in the cattle industry worldwide. It shows its effect through immunosuppression and develops persistent infection in calves born from infected cows. The current study revealed that BVDV potentially induced immunosuppression by the interaction of BVDV Npro protein with cellular S100A9 protein. The Inhibition of S100A9 protein expression by small interfering RNA (siRNA) enhanced the virus replication in infected cells. Overexpression of bovine S100A9 enhanced the ncpBVDV2a 1373 mediated Type-I interferon production. A co-immunoprecipitation experiment demonstrated a strong interaction between ncp BVDV2a 1373 Npro protein and cellular S100A9 protein. This suggested that BVDV Npro reduced the S100A9 protein availability/activity in infected cells, resulting in reduced Type-I interferon production. A further study of S100A9-BVDV interaction will be need for better understanding of BVDV pathophysiology.