How Low Cholesterol Is Good for Anti-viral Immunity Luke A.J. O’Neill  Cell  Volume 163, Issue 7, Pages 1572-1574 (December 2015) DOI: 10.1016/j.cell.2015.12.004 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 Decreased Cholesterol Biosynthesis Facilitates Anti-viral Signaling by STING in the ER Viruses such as MHV-68, HIV1, and influenza or the TLR3 ligand poly:IC or the TLR4 ligand LPS induce IFN β and decrease cholesterol biosynthesis via an unknown mechanism. This is likely to deplete cholesterol in the ER membrane. The resulting altered “lipid code” facilitates STING activation, which occurs in response to the second messenger cGAMP, generated by cGAS activated by viral DNA. STING then activates TBK-1, leading to IRF3 phosphorylation and induction of further IFN β and other IFN-sensitive genes important for anti-viral immunity. IFN β might feedback and cause a further decrease in cholesterol biosynthesis, potentiating its own induction. Cell 2015 163, 1572-1574DOI: (10.1016/j.cell.2015.12.004) Copyright © 2015 Elsevier Inc. Terms and Conditions