SARS-CoV-2–associated ssRNAs activate inflammation and immunity via TLR7/8

Abstract

The inflammatory and IFN pathways of innate immunity play a key role in the resistance and pathogenesis of coronavirus disease 2019 (COVID-19). Innate sensors and SARS-CoV-2–associated molecular patterns (SAMPs) remain to be completely defined. Here, we identified single-stranded RNA (ssRNA) fragments from the SARS-CoV-2 genome as direct activators of endosomal TLR7/8 and MyD88 pathway. The same sequences induced human DC activation in terms of phenotype and function, such as IFN and cytokine production and Th1 polarization. A bioinformatic scan of the viral genome identified several hundreds of fragments potentially activating TLR7/8, suggesting that products of virus endosomal processing potently activate the IFN and inflammatory responses downstream of these receptors. In vivo, SAMPs induced MyD88-dependent lung inflammation characterized by accumulation of proinflammatory and cytotoxic mediators and immune cell infiltration, as well as splenic DC phenotypical maturation. These results identified TLR7/8 as a crucial cellular sensor of ssRNAs encoded by SARS-CoV-2 involved in host resistance and the disease pathogenesis of COVID-19.

References 58

1. 1.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

2. 2.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

3. 3.
   Human Immunodeficiency Virus Type 1 Nef Inhibits Autophagy through Transcription Factor EB Sequestration · 2015

   No notice
4. 4.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

5. 5.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

6. 6.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

7. 7.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

8. 8.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

9. 9.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

10. 10.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

11. 11.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

12. 12.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

13. 13.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

14. 14.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

15. 15.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

16. 16.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

17. 17.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

18. 18.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

19. 19.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

20. 20.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

21. 21.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

22. 22.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

23. 23.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

24. 24.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

25. 25.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

26. 26.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

27. 27.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

28. 28.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

29. 29.
    Expression Atlas: gene and protein expression across multiple studies and organisms · 2017

    No notice
30. 30.
    Human dendritic cell subsets: an update · 2018

    No notice
31. 31.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

32. 32.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

33. 33.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

34. 34.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

35. 35.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

36. 36.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

37. 37.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

38. 38.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

39. 39.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

40. 40.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

Cited by papers we hold 2

• Mucosal immune response in biology, disease prevention and treatment · 2025
  No notice
• Detection of Leptomonas seymouri narna-like virus in serum samples of visceral leishmaniasis patients and its possible role in disease pathogenesis · 2022
  Not checked

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.