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

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.

• Authors: Katrina B Mar, Nicholas R Rinkenberger, Ian N Boys, Jennifer L Eitson, Matthew B McDougal, R Blake Richardson, John W Schoggins
• Journal: Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 3603 (09 06 2018) ISSN: 2041-1723 [Electronic] England
• PMID: 30190477 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• GPI-Linked Proteins
• LY6E protein, human
• Interferons
• Leucine

Topics

• Animals
• Antigens, Surface (genetics, metabolism)
• Biological Evolution
• Cell Line
• Fibroblasts (virology)
• GPI-Linked Proteins (genetics, metabolism)
• Gene Expression Regulation
• Host-Pathogen Interactions (physiology)
• Humans
• Influenza A virus (pathogenicity)
• Interferons (genetics, metabolism)
• Leucine
• RNA Virus Infections (metabolism)
• RNA Viruses (pathogenicity, physiology)
• Virus Internalization
• Virus Replication
• Yellow fever virus (pathogenicity)