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.

Leishmania exosomes function as viral envelopes

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.

New research from McGill University has found that a virus infecting the Leishmania parasite spreads by exploiting a mechanism used for cell-to-cell communication, a discovery that could pave the way to new vaccines against infections that cause severe disfiguration. Much like animals, viruses evolve to improve their chances of survival. Every year, the influenza virus spreads by changing key proteins on its surface to trick our immune system into thinking that it never encountered the pathogen. The herpes simplex virus, on the other hand, lies hidden in the brain; an area that is off limits to our body’s defences — until the next time it is ready to attack.

“Communication pods”

Martin Olivier, a senior scientist from the Infectious Diseases and Immunity in Global Health Program at the Research Institute of the McGill University Health Centre, has recently shown that a virus that infects a primitive type of cell — the Leishmania parasite — also has a ruse to avoid detection. In a study recently published in Nature Microbiology, Olivier found that the Leishmania RNA virus 1 (LRV1) hides in tiny vessels — known as exosomes — that Leishmania parasites use to “communicate” among themselves. “This is the first time that a non-enveloped double stranded RNA virus; shown to be capable of exploiting lower eukaryotic exosomes to gain an envelope,” says Prof. Olivier, who is also a full Professor of Microbiology and Immunology.

“By hiding in these ‘communication pods;‘ the virus has the protection from external threats; and the infection of other Leishmania cells has the facilitation.” Olivier and his colleagues also showed that; leishmaniasis cases were significantly more aggressive; when parasites had the infection of LRV1.”This provides us with a new model to study virus biology; and mechanisms regulating virus release from host cells,” Olivier adds. “Ultimately, the use of Leishmania exosomes; containing the virus could lead to an effective vaccine against Leishmania viannia guyanensis; a particular strain of Leishmania that causes a with LRV1.”The Leishmania parasite; mostly found in tropical areas; transmitted by the female sandfly; and leads to about 1 million cases of leishmaniasis yearly; killing thousands and leaving many others disfigured.