Abstract Title:

Exosome mimicry by a HAVCR1-NPC1 pathway of endosomal fusion mediates hepatitis A virus infection.

Abstract Source:

Nat Microbiol. 2020 Sep ;5(9):1096-1106. Epub 2020 Jun 15. PMID: 32541946

Abstract Author(s):

Maria Isabel Costafreda, Abdolrahim Abbasi, Hsinyi Lu, Gerardo Kaplan

Article Affiliation:

Maria Isabel Costafreda


Cell-to-cell communication by exosomes controls normal and pathogenic processes. Viruses can spread in exosomes and thereby avoid immune recognition. While biogenesis, binding and uptake of exosomes are well characterized, delivery of exosome cargo into the cytoplasm is poorly understood. We report that the phosphatidylserine receptor HAVCR1 (refs.) and the cholesterol transporter NPC1 (ref.) participate in cargo delivery from exosomes of hepatitis A virus (HAV)-infected cells (exo-HAV) by clathrin-mediated endocytosis. Using CRISPR-Cas9 knockout technology, we show that these two lipid receptors, which interact in the late endosome, are necessary for the membrane fusion and delivery of RNA from exo-HAV into the cytoplasm. The HAVCR1-NPC1 pathway, which Ebola virus exploits to infect cells, mediates HAV infection by exo-HAV, which indicates that viral infection via this exosome mimicry mechanism does not require an envelope glycoprotein. The capsid-free viral RNA in the exosome lumen, but not the endosomal uncoating of HAV particles contained in the exosomes, is mainly responsible for exo-HAV infectivity as assessed by methylene blue inactivation of non-encapsidated RNA. In contrast to exo-HAV, infectivity of HAV particles is pH-independent and requires HAVCR1 or another as yet unidentified receptor(s) but not NPC1. Our findings show that envelope-glycoprotein-independent fusion mechanisms are shared by exosomes and viruses, and call for a reassessment of the role of envelope glycoproteins in infection.

Study Type : In Vitro Study
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Additional Keywords : Exosomes : CK(312) : AC(199)

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