Open AccessChikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS
Author(s) -
Laurence G. Webb,
Jeury Veloz,
Jessica Pintado-Silva,
Tongtong Zhu,
Margarita V. Rangel,
Tinaye Mutetwa,
L. Zhang,
Dabeiba Bernal-Rubio,
Debbie M. Figueroa,
Lucía Carrau,
Rafael Fenutría,
Uma Potla,
St Patrick Reid,
Jacob S. Yount,
Kenneth A. Stapleford,
Sebastián Aguirre,
Ana Fernández-Sesma
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008999
Subject(s) - interferon , biology , chikungunya , signal transducing adaptor protein , virology , virus , alphavirus , viral replication , microbiology and biotechnology , stimulator of interferon genes , capsid , dna virus , innate immune system , signal transduction , gene , immune system , genetics , genome
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which in rare cases cause long term debilitating arthritis and arthralgia. Significant progress has been made in understanding the roles of canonical RNA sensing pathways in the host recognition of CHIKV; however, less is known regarding antagonism of CHIKV by cytosolic DNA sensing pathways like that of cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). With the use of cGAS or STING null cells we demonstrate that the pathway restricts CHIKV replication in fibroblasts and immune cells. We show that DNA accumulates in the cytoplasm of infected cells and that CHIKV blocks DNA dependent IFN-β transcription. This antagonism of DNA sensing is via an early autophagy-mediated degradation of cGAS and expression of the CHIKV capsid protein is sufficient to induce cGAS degradation. Furthermore, we identify an interaction of CHIKV nsP1 with STING and map the interaction to 23 residues in the cytosolic loop of the adaptor protein. This interaction stabilizes the viral protein and increases the level of palmitoylated nsP1 in cells. Together, this work supports previous publications highlighting the relevance of the cGAS-STING pathway in the early detection of (+)ssRNA viruses and provides direct evidence that CHIKV interacts with and antagonizes cGAS-STING signaling.