Department of Biochemistry, University of Lausanne, Epalinges, Vaud, Switzerland.
Department of Microbiology, Immunology & Parasitology, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
PLoS Negl Trop Dis. 2014 Apr 24;8(4):e2836. doi: 10.1371/journal.pntd.0002836. eCollection 2014 Apr.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
利什曼原虫感染主要导致沙蝇叮咬部位的皮肤损伤。已经报道了莱什曼物种（如 L. braziliensis、guyanensis 和 aethiopica）的炎症转移性形式。对于导致这种加剧的临床表现的因素知之甚少。利什曼 RNA 病毒（LRV）主要存在于南美的 L. braziliensis 和 guyanensis 中。在 L. guyanensis 感染的小鼠模型中，其存在导致宿主 Toll 样受体 3 识别病毒 dsRNA 基因组，导致炎症反应过度，从而加剧疾病。在一个实例中，LRV 在南美洲以外的地方被报道，即来自土库曼斯坦的 L. major ASKH 株，表明 LRV 出现在利什曼亚属分化之前。LRV 在利什曼原虫内的存在可能是疾病严重程度的相关因素之一，为在 L. aethiopica 中进行 LRV 筛查提供了依据。
方法/主要发现：在四个 L. aethiopica 株（LRV-Lae）中鉴定出一个新的 LRV 成员。对三个 LRV-Lae 基因组进行测序，并与 L. guyanensis LRV1 和 L. major LRV2 进行比较。LRV-Lae 更类似于 LRV2。尽管它们的基因组组织相似，但在衣壳蛋白和病毒聚合酶开放阅读框重叠的区域观察到一个显著的差异，LRV-Lae 中存在独特的-1 情况。体外感染小鼠巨噬细胞表明，LRV-Lae 诱导了 TLR3 依赖性炎症反应，如先前观察到的 LRV1 一样。
结论/意义：在这项研究中，我们报告了在 L. aethiopica 人类分离株中存在一种免疫性 dsRNA 病毒。这是在非洲首次观察到 LRV，与在土库曼斯坦独特描述的 LRV2 一起，证实了 LRV 存在于 L.（Leishmania）和（Viannia）亚属分化之前。讨论了 LRV-Lae 对由 L. aethiopica 感染引起的疾病严重程度的潜在影响。
