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

Publication ,  Journal Article
Biering, SB; Choi, J; Halstrom, RA; Brown, HM; Beatty, WL; Lee, S; McCune, BT; Dominici, E; Williams, LE; Orchard, RC; Wilen, CB; Yamamoto, M ...
Published in: Cell Host Microbe
July 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.

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

July 12, 2017

Volume

22

Issue

1

Start / End Page

74 / 85.e7

Location

United States

Related Subject Headings

  • Virus Replication
  • Viral Plaque Assay
  • Vacuoles
  • RAW 264.7 Cells
  • Norovirus
  • Microtubule-Associated Proteins
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Macrophages
 

Citation

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Biering, S. B., Choi, J., Halstrom, R. A., Brown, H. M., Beatty, W. L., Lee, S., … Hwang, S. (2017). Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases. Cell Host Microbe, 22(1), 74-85.e7. https://doi.org/10.1016/j.chom.2017.06.005
Biering, Scott B., Jayoung Choi, Rachel A. Halstrom, Hailey M. Brown, Wandy L. Beatty, Sanghyun Lee, Broc T. McCune, et al. “Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases.Cell Host Microbe 22, no. 1 (July 12, 2017): 74-85.e7. https://doi.org/10.1016/j.chom.2017.06.005.
Biering SB, Choi J, Halstrom RA, Brown HM, Beatty WL, Lee S, et al. Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases. Cell Host Microbe. 2017 Jul 12;22(1):74-85.e7.
Biering, Scott B., et al. “Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases.Cell Host Microbe, vol. 22, no. 1, July 2017, pp. 74-85.e7. Pubmed, doi:10.1016/j.chom.2017.06.005.
Biering SB, Choi J, Halstrom RA, Brown HM, Beatty WL, Lee S, McCune BT, Dominici E, Williams LE, Orchard RC, Wilen CB, Yamamoto M, Coers J, Taylor GA, Hwang S. Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases. Cell Host Microbe. 2017 Jul 12;22(1):74-85.e7.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

July 12, 2017

Volume

22

Issue

1

Start / End Page

74 / 85.e7

Location

United States

Related Subject Headings

  • Virus Replication
  • Viral Plaque Assay
  • Vacuoles
  • RAW 264.7 Cells
  • Norovirus
  • Microtubule-Associated Proteins
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Macrophages