Viruses PLAY DEAD to TAMe interferon responses

Abstract

TAM receptors promote apoptotic cell uptake and function as inflammation suppressors. Many viruses mimic apoptotic cells, thus exploiting TAM receptors for attachment and entry. In this issue of Cell Host & Microbe, Bhattacharyya et al. show that TAM binding by enveloped viruses also induces receptor signaling to suppress cellular interferon responses.

Figure 1. TAM receptors promote virus replication by two distinct mechanisms

Enveloped viruses display phosphatidylserine to engage the TAM receptor ligands, Gas6 or Protein S, and bind TAM receptors to facilitate virus attachment to a cell and entry. Virus ligation of TAM receptors also promotes receptor activation which, through cooperation with the IFN-I receptor (IFNAR),inducesSOCS1 and SOCS3 expression. SOCS1/3 are important negative regulators of IFN and cytokine signaling. In particular, SOCS upregulation in DCs resulted in decreased expression of genes associated with type I IFN production, including IRF5, IRF7, IFNβ and IFNα4, thereby blunting the innate antiviral response and promoting virus replication.