LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step

Katrina B. Mar, Nicholas R. Rinkenberger, Ian N. Boys, Jennifer L. Eitson, Matthew B. McDougal, R. Blake Richardson, John W. Schoggins

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Interferons (IFNs) contribute to cell-intrinsic antiviral immunity by inducing hundreds of interferon-stimulated genes (ISGs). In a screen to identify antiviral ISGs, we unexpectedly found that LY6E, a member of the LY6/uPAR family, enhanced viral infection. Here, we show that viral enhancement by ectopically expressed LY6E extends to several cellular backgrounds and affects multiple RNA viruses. LY6E does not impair IFN antiviral activity or signaling, but rather promotes viral entry. Using influenza A virus as a model, we narrow the enhancing effect of LY6E to uncoating after endosomal escape. Diverse mammalian orthologs of LY6E also enhance viral infectivity, indicating evolutionary conservation of function. By structure-function analyses, we identify a single amino acid in a predicted loop region that is essential for viral enhancement. Our study suggests that LY6E belongs to a class of IFN-inducible host factors that enhance viral infectivity without suppressing IFN antiviral activity.

Original languageEnglish (US)
Article number3603
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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interferon
viruses
infectious diseases
Virus Diseases
Viruses
entry
Interferons
Antiviral Agents
augmentation
genes
Genes
influenza
RNA Viruses
Influenza A virus
immunity
escape
amino acids
conservation
Immunity
Conservation

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step. / Mar, Katrina B.; Rinkenberger, Nicholas R.; Boys, Ian N.; Eitson, Jennifer L.; McDougal, Matthew B.; Richardson, R. Blake; Schoggins, John W.

In: Nature Communications, Vol. 9, No. 1, 3603, 01.12.2018.

Research output: Contribution to journalArticle

Mar, Katrina B. ; Rinkenberger, Nicholas R. ; Boys, Ian N. ; Eitson, Jennifer L. ; McDougal, Matthew B. ; Richardson, R. Blake ; Schoggins, John W. / LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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