Format

Send to

Choose Destination
Nat Commun. 2018 Nov 19;9(1):4841. doi: 10.1038/s41467-018-07314-7.

RIG-I like receptor sensing of host RNAs facilitates the cell-intrinsic immune response to KSHV infection.

Author information

1
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, 37232-2363, USA.
2
College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan Province, 453000, China.
3
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, 37232-2363, USA. john.karijolich@vanderbilt.edu.
4
Vanderbilt-Ingram Cancer Center, Nashville, TN, 37232-2363, USA. john.karijolich@vanderbilt.edu.
5
Vanderbilt Institute for Infection, Immunology and Inflammation, Nashville, TN, 37232-2363, USA. john.karijolich@vanderbilt.edu.

Abstract

The RIG-I like receptors (RLRs) RIG-I and MDA5 are cytosolic RNA helicases best characterized as restriction factors for RNA viruses. However, evidence suggests RLRs participate in innate immune recognition of other pathogens, including DNA viruses. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus and the etiological agent of Kaposi's sarcoma and primary effusion lymphoma (PEL). Here, we demonstrate that RLRs restrict KSHV lytic reactivation and we demonstrate that restriction is facilitated by the recognition of host-derived RNAs. Misprocessed noncoding RNAs represent an abundant class of RIG-I substrates, and biochemical characterizations reveal that an infection-dependent reduction in the cellular triphosphatase DUSP11 results in an accumulation of select triphosphorylated noncoding RNAs, enabling their recognition by RIG-I. These findings reveal an intricate relationship between RNA processing and innate immunity, and demonstrate that an antiviral innate immune response can be elicited by the sensing of misprocessed cellular RNAs.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center