Loss of RIG-I leads to a functional replacement with MDA5 in the Chinese tree shrew.
The function of the RIG-I-like receptors (RLRs; including RIG-I, MDA5, and LGP2) as key cytoplasmic sensors of viral pathogen-associated molecular patterns (PAMPs) has been subjected to numerous pathogenic challenges and has undergone a dynamic evolution. We found evolutionary evidence that RIG-I was lost in the Chinese tree shrew lineage. Along with the loss of RIG-I, both MDA5 (tMDA5) and LGP2 (tLGP2) have undergone strong positive selection in the tree shrew. tMDA5 or tMDA5/tLGP2 could sense Sendai virus (an RNA virus posed as a RIG-I agonist) for inducing type I IFN, although conventional RIG-I and MDA5 were thought to recognize distinct RNA structures and viruses. tMDA5 interacted with adaptor tMITA (STINGTMEM173/ERIS), which was reported to bind only with RIG-I. The positively selected sites in tMDA5 endowed the substitute function for the lost RIG-I. These findings provided insights into the adaptation and functional diversity of innate antiviral activity in vertebrates.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China;
Ling
L
Xu
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China;
Dandan
D
Yu
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China;
Yu
Y
Fan
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China;
Li
L
Peng
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China;
Yong
Y
Wu
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China; Kunming Primate Research Center of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China yaoyg@mail.kiz.ac.cn.
Yong-Gang
YG
Yao
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D053487:DEAD-box RNA Helicases / Q000172:deficiency* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1 / Q000737:chemistry / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D008024:Ligands; D008565:Membrane Proteins; D050505:Mutant Proteins / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D012328:RNA Viruses / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012641:Selection, Genetic; D012788:Shrews / Q000235:genetics / Q000378:metabolism* / Q000821:virology
D008024:Ligands; D008565:Membrane Proteins; D050505:Mutant Proteins; D012367:RNA, Viral; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1
MDA5; RIG-I; functional replacement; positive selection; tree shrew