Type I interferons have critical antiviral functions, but their main cellular targets are unclear. In PLOS Pathogens, Diamond and colleagues use conditional deletion of the receptor for type I interferons (IFNAR) to determine the key cells that require signaling via type I interferons to mediate resistance to infection with West Nile Virus (WNV). As expected, germline deletion of IFNAR leads to rapid death after WNV infection but, unexpectedly, conditional deletion of IFNAR specifically in dendritic cells, granulocytes, macrophages or monocytes results in an equally severe pathology. The morbidity of WNV-infected mice with germline or conditional deletion of IFNAR is due to sepsis and includes elevated viral loads and cytokine production by IFNAR-deficient cells. The signaling adaptor MAVS is at the vertex of several key antiviral recognition pathways, and deletion of MAVS in conjunction with deletion of IFNAR largely normalizes cytokine production but leaves WNV loads high. The action of type I interferons in myeloid cells, therefore, is essential in controlling the permissiveness and pathology of WNV.

PLoS Pathog. (17 April 2014) doi:10.1371/journal.ppat.1004086