Leishmania aethiopica field isolates bearing an endosymbiontic dsRNA virus induce pro-inflammatory cytokine response.
BACKGROUND
Infection with Leishmania parasites causes mainly cutaneous lesions at the site of the sand fly bite. Inflammatory metastatic forms have been reported with Leishmania species such as L. braziliensis, guyanensis and aethiopica. Little is known about the factors underlying such exacerbated clinical presentations. Leishmania RNA virus (LRV) is mainly found within South American Leishmania braziliensis and guyanensis. In a mouse model of L. guyanensis infection, its presence is responsible for an hyper-inflammatory response driven by the recognition of the viral dsRNA genome by the host Toll-like Receptor 3 leading to an exacerbation of the disease. In one instance, LRV was reported outside of South America, namely in the L. major ASKH strain from Turkmenistan, suggesting that LRV appeared before the divergence of Leishmania subgenera. LRV presence inside Leishmania parasites could be one of the factors implicated in disease severity, providing rationale for LRV screening in L. aethiopica.


RESULTS
A new LRV member was identified in four L. aethiopica strains (LRV-Lae). Three LRV-Lae genomes were sequenced and compared to L. guyanensis LRV1 and L. major LRV2. LRV-Lae more closely resembled LRV2. Despite their similar genomic organization, a notable difference was observed in the region where the capsid protein and viral polymerase open reading frames overlap, with a unique -1 situation in LRV-Lae. In vitro infection of murine macrophages showed that LRV-Lae induced a TLR3-dependent inflammatory response as previously observed for LRV1.


CONCLUSIONS
In this study, we report the presence of an immunogenic dsRNA virus in L. aethiopica human isolates. This is the first observation of LRV in Africa, and together with the unique description of LRV2 in Turkmenistan, it confirmed that LRV was present before the divergence of the L. (Leishmania) and (Viannia) subgenera. The potential implication of LRV-Lae on disease severity due to L. aethiopica infections is discussed.
Department of Biochemistry, University of Lausanne, Epalinges, Vaud, Switzerland.
Haroun
H
Zangger
Department of Microbiology, Immunology & Parasitology, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
Asrat
A
Hailu
Department of Biochemistry, University of Lausanne, Epalinges, Vaud, Switzerland.
Chantal
C
Desponds
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Lon-Fye
LF
Lye
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Natalia S
NS
Akopyants
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Deborah E
DE
Dobson
Department of Biochemistry, University of Lausanne, Epalinges, Vaud, Switzerland.
Catherine
C
Ronet
Department of Biochemistry, University of Lausanne, Epalinges, Vaud, Switzerland.
Hashim
H
Ghalib
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Stephen M
SM
Beverley
Department of Biochemistry, University of Lausanne, Epalinges, Vaud, Switzerland.
Nicolas
N
Fasel
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D005002:Ethiopia; D006801:Humans; D007891:Leishmania / Q000276:immunology* / Q000302:isolation & purification / Q000821:virology*; D007896:Leishmaniasis / Q000469:parasitology; D051379:Mice; D008969:Molecular Sequence Data; D012328:RNA Viruses / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA
D016207:Cytokines; D012367:RNA, Viral