Low compositions of human toll-like receptor 7/8-stimulating RNA motifs in the MERS-CoV, SARS-CoV and SARS-CoV-2 genomes imply a substantial ability to evade human innate immunity.

BACKGROUND: The innate immune system especially Toll-like receptor (TLR) 7/8 and the interferon pathway, constitutes an important first line of defense against single-stranded RNA viruses. However, large-scale, systematic comparisons of the TLR 7/8-stimulating potential of genomic RNAs of single-stranded RNA viruses are rare. In this study, a computational method to evaluate the human TLR 7/8-stimulating ability of single-stranded RNA virus genomes based on their human TLR 7/8-stimulating trimer compositions was used to analyze 1,002 human coronavirus genomes. RESULTS: The human TLR 7/8-stimulating potential of coronavirus genomic (positive strand) RNAs followed the order of NL63-CoV > HKU1-CoV >229E-CoV ≅ OC63-CoV > SARS-CoV-2 > MERS-CoV > SARS-CoV. These results suggest that among these coronaviruses, MERS-CoV, SARS-CoV and SARS-CoV-2 may have a higher ability to evade the human TLR 7/8-mediated innate immune response. Analysis with a logistic regression equation derived from human coronavirus data revealed that most of the 1,762 coronavirus genomic (positive strand) RNAs isolated from bats, camels, cats, civets, dogs and birds exhibited weak human TLR 7/8-stimulating potential equivalent to that of the MERS-CoV, SARS-CoV and SARS-CoV-2 genomic RNAs. CONCLUSIONS: Prediction of the human TLR 7/8-stimulating potential of viral genomic RNAs may be useful for surveillance of emerging coronaviruses from nonhuman mammalian hosts.