Abstract
BackgroundInfection 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.Methodology/Principal FindingsA 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/SignificanceIn 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.
Highlights
In the highlands of Ethiopia, patients infected with L. aethiopica mostly develop localized cutaneous lesions, which can self heal
Using several approaches to detect Leishmania RNA virus (LRV) in whole parasite isolates [28], we showed that some strains freshly isolated from human patients infected with L. aethiopica contained a double stranded RNA (dsRNA) virus
A complete LRV-L. aethiopica (Lae) genome was obtained for one isolate, and more than 97% of it, including the capsid protein (CP)-RNA-dependent RNA polymerase (RdRp) regions, for two others
Summary
In the highlands of Ethiopia, patients infected with L. aethiopica mostly develop localized cutaneous lesions, which can self heal. CL tends to persist and to metastasize to other parts of the body causing mucosal leishmaniasis (ML) or diffuse cutaneous leishmaniasis (DCL), two different clinical presentations. ML patients begin with a single lesion, but in this case infection metastasizes to mucosal tissue causing chronic inflammation and facial disfiguring lesions. 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. LRV presence inside Leishmania parasites could be one of the factors implicated in disease severity, providing rationale for LRV screening in L. aethiopica
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