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Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases.

Cell host & microbe | Jul 12, 2017

All viruses with positive-sense RNA genomes replicate on membranous structures in the cytoplasm called replication complexes (RCs). RCs provide an advantageous microenvironment for viral replication, but it is unknown how the host immune system counteracts these structures. Here we show that interferon-gamma (IFNG) disrupts the RC of murine norovirus (MNV) via evolutionarily conserved autophagy proteins and the induction of IFN-inducible GTPases, which are known to destroy the membrane of vacuoles containing bacteria, protists, or fungi. The MNV RC was marked by the microtubule-associated-protein-1-light-chain-3 (LC3) conjugation system of autophagy and then targeted by immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs) upon their induction by IFNG. Further, the LC3 conjugation system and the IFN-inducible GTPases were necessary to inhibit MNV replication in mice and human cells. These data suggest that viral RCs can be marked and antagonized by a universal immune defense mechanism targeting diverse pathogens replicating in cytosolic membrane structures.

Pubmed ID: 28669671 RIS Download

Mesh terms: Animals | Autophagy | Caliciviridae Infections | Carrier Proteins | Cell Line | Cytosol | Female | Fibroblasts | GTP Phosphohydrolases | Gene Knockdown Techniques | HeLa Cells | Humans | Immunity, Innate | Interferon-gamma | Interferons | Macrophages | Male | Mice | Mice, Inbred C57BL | Microtubule-Associated Proteins | Norovirus | RAW 264.7 Cells | Vacuoles | Viral Plaque Assay | Virus Replication

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Associated grants

  • Agency: NCATS NIH HHS, Id: UL1 TR000430
  • Agency: NIDDK NIH HHS, Id: P30 DK042086
  • Agency: NIAID NIH HHS, Id: R01 AI103197
  • Agency: NCI NIH HHS, Id: P30 CA014599
  • Agency: NCI NIH HHS, Id: F31 CA177194
  • Agency: NIAID NIH HHS, Id: T32 AI007090
  • Agency: NIAID NIH HHS, Id: K08 AI128043
  • Agency: BLRD VA, Id: I01 BX002369
  • Agency: NIGMS NIH HHS, Id: T32 GM007183

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