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Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B.

Publication ,  Journal Article
Lennemann, NJ; Coyne, CB
Published in: Autophagy
February 2017

The endoplasmic reticulum (ER) is exploited by several diverse viruses during their infectious life cycles. Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), utilize the ER as a source of membranes to establish their replication organelles and to facilitate their assembly and eventual maturation along the secretory pathway. To maintain normal homeostasis, host cells have evolved highly efficient processes to dynamically regulate the ER, such as through reticulophagy, a selective form of autophagy that leads to ER degradation. Here, we identify the ER-localized reticulophagy receptor FAM134B as a host cell restriction factor for both DENV and ZIKV. We show that RNAi-mediated depletion of FAM134B significantly enhances both DENV and ZIKV replication at an early stage of the viral life cycle. Consistent with its role as an antiviral host factor, we found that several flaviviruses including DENV, ZIKV, and West Nile virus (WNV), utilize their NS3 virally-encoded proteases to directly cleave FAM134B at a single site within its reticulon homology domain (RHD). Mechanistically, we show that NS3-mediated cleavage of FAM134B blocks the formation of ER and viral protein-enriched autophagosomes, suggesting that the cleavage of FAM134B serves to specifically suppress the reticulophagy pathway. These findings thus point to an important role for FAM134B and reticulophagy in the regulation of flavivirus infection and suggest that these viruses specifically target these pathways to promote viral replication.

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Published In

Autophagy

DOI

EISSN

1554-8635

Publication Date

February 2017

Volume

13

Issue

2

Start / End Page

322 / 332

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Viral Proteins
  • Serine Endopeptidases
  • Neoplasm Proteins
  • Models, Biological
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Hela Cells
 

Citation

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Lennemann, N. J., & Coyne, C. B. (2017). Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B. Autophagy, 13(2), 322–332. https://doi.org/10.1080/15548627.2016.1265192
Lennemann, Nicholas J., and Carolyn B. Coyne. “Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B.Autophagy 13, no. 2 (February 2017): 322–32. https://doi.org/10.1080/15548627.2016.1265192.
Lennemann NJ, Coyne CB. Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B. Autophagy. 2017 Feb;13(2):322–32.
Lennemann, Nicholas J., and Carolyn B. Coyne. “Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B.Autophagy, vol. 13, no. 2, Feb. 2017, pp. 322–32. Pubmed, doi:10.1080/15548627.2016.1265192.
Lennemann NJ, Coyne CB. Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B. Autophagy. 2017 Feb;13(2):322–332.

Published In

Autophagy

DOI

EISSN

1554-8635

Publication Date

February 2017

Volume

13

Issue

2

Start / End Page

322 / 332

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Viral Proteins
  • Serine Endopeptidases
  • Neoplasm Proteins
  • Models, Biological
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Hela Cells