Format

Send to

Choose Destination
Nat Microbiol. 2019 Jan 28. doi: 10.1038/s41564-018-0352-y. [Epub ahead of print]

Exploitation of the Leishmania exosomal pathway by Leishmania RNA virus 1.

Author information

1
Department of Medicine, Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
2
Infectious Diseases and Immunity in Global Heath Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
3
Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada.
4
Department of Medicine, Microbiology and Immunology, McGill University, Montreal, Quebec, Canada. martin.olivier@mcgill.ca.
5
Infectious Diseases and Immunity in Global Heath Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. martin.olivier@mcgill.ca.

Abstract

Leishmania are ancient eukaryotes that have retained the exosome pathway through evolution. Leishmania RNA virus 1 (LRV1)-infected Leishmania species are associated with a particularly aggressive mucocutaneous disease triggered in response to the double-stranded RNA (dsRNA) virus. However, it is unclear how LRV1 is exposed to the mammalian host cells. In higher eukaryotes, some viruses are known to utilize the host exosome pathway for their formation and cell-to-cell spread. As a result, exosomes derived from infected cells contain viral material or particles. Herein, we investigated whether LRV1 exploits the Leishmania exosome pathway to reach the extracellular environment. Biochemical and electron microscopy analyses of exosomes derived from LRV1-infected Leishmania revealed that most dsRNA LRV1 co-fractionated with exosomes, and that a portion of viral particles was surrounded by these vesicles. Transfer assays of LRV1-containing exosome preparations showed that a significant amount of parasites were rapidly and transiently infected by LRV1. Remarkably, these freshly infected parasites generated more severe lesions in mice than non-infected ones. Moreover, mice co-infected with parasites and LRV1-containing exosomes also developed a more severe disease. Overall, this work provides evidence that Leishmania exosomes function as viral envelopes, thereby facilitating LRV1 transmission and increasing infectivity in the mammalian host.

PMID:
30692670
DOI:
10.1038/s41564-018-0352-y

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center