Negative regulation of MAVS-mediated innate immune response by ASC

Mol Cell Biochem. 2018 Aug;445(1-2):35-43. doi: 10.1007/s11010-017-3249-9. Epub 2017 Dec 26.

Abstract

Stringent control of the type I interferon signaling pathways is critical to effective host immune responses, however, the molecular mechanisms that negatively regulate these pathways are still poorly understood. Here, we show that apoptosis speck-like protein (ASC), an adaptor protein of inflammasome complex, can inhibit IFN-β signaling response by interacting with mitochondrial antiviral signaling protein (MAVS). Importantly, ASC-specific siRNA knockdown enhanced virus-induced type I interferon production, with consequent reduction of virus replication. Taken together, these results suggest that ASC, as a negative regulator of the MAVS-mediated innate immunity, may play an important role in host protection upon virus infection.

Keywords: ASC; Innate immunity; MAVS.

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / physiology*
  • Cells, Cultured
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate / physiology*
  • Inflammasomes / physiology
  • Interferon-beta / genetics
  • Interferon-beta / metabolism
  • MCF-7 Cells
  • Mice
  • RNA, Small Interfering / genetics
  • Signal Transduction / physiology
  • Virus Diseases / immunology
  • Virus Diseases / prevention & control
  • Virus Replication / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • CARD Signaling Adaptor Proteins
  • Inflammasomes
  • MAVS protein, human
  • PYCARD protein, human
  • RNA, Small Interfering
  • Interferon-beta