The STING-MSR1 Axis Controls RNA Virus Infection Through Noncanonical Autophagy

The stimulator-of-interferon-gene (STING) pathway controls both DNA and RNA virus infection. STING is critical for induction of type I interferons (IFN-I) during DNA virus infection, while the molecular mechanism underlying the anti-RNA virus function of STING remains largely elusive. We show that the STING signaling pathway regulates expression of macrophage scavenger receptor 1 (MSR1), which activates a cell-intrinsic antiviral mechanism through autophagy related ATG5-ATG12. Mice deficient in Sting or Msr1 had increased viral replication and susceptibility to Chikungunya virus (CHIKV)-induced arthritis. Repression of CHIKV replication by MSR1 was dependent on ATG5-ATG12, but independent of other autophagy components such as ULK1 and Beclin 1. MSR1 interacted with ATG5–ATG12 following CHIKV infection, and this interaction was independent of canonical autophagy. Induction of MSR1 expression by CHIKV was partially dependent on the STING signaling. Our results elucidate an antiviral role of the STING-MSR1 axis involving the non-canonical autophagy-related function of ATG5-ATG12.