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

Author

Listed:
  • Yang Zhao

    (Vanderbilt University School of Medicine)

  • Xiang Ye

    (Vanderbilt University School of Medicine)

  • William Dunker

    (Vanderbilt University School of Medicine)

  • Yu Song

    (Vanderbilt University School of Medicine
    Xinxiang Medical University)

  • John Karijolich

    (Vanderbilt University School of Medicine
    Vanderbilt-Ingram Cancer Center
    Vanderbilt Institute for Infection, Immunology and Inflammation)

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.

Suggested Citation

  • Yang Zhao & Xiang Ye & William Dunker & Yu Song & John Karijolich, 2018. "RIG-I like receptor sensing of host RNAs facilitates the cell-intrinsic immune response to KSHV infection," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07314-7
    DOI: 10.1038/s41467-018-07314-7
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    Cited by:

    1. Suba Rajendren & Xiang Ye & William Dunker & Antiana Richardson & John Karijolich, 2023. "The cellular and KSHV A-to-I RNA editome in primary effusion lymphoma and its role in the viral lifecycle," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Takayoshi Shirasaki & Satoshi Yamagoe & Tetsuro Shimakami & Kazuhisa Murai & Ryu Imamura & Kiyo-Aki Ishii & Hiroaki Takayama & Yukako Matsumoto & Natsumi Tajima-Shirasaki & Naoto Nagata & Ryogo Shimiz, 2022. "Leukocyte cell-derived chemotaxin 2 is an antiviral regulator acting through the proto-oncogene MET," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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