Kariyawasam Ruwandi, Grewal Jugvinder, Lau Rachel, Purssell Andrew, Valencia Braulio M, Llanos-Cuentas Alejandro, Boggild Andrea K
Institute of Medical Science, University of Toronto, Ontario.
Public Health Ontario Laboratories, Toronto, Canada.
J Infect Dis. 2017 Oct 17;216(7):877-886. doi: 10.1093/infdis/jix416.
Species of the Leishmania Viannia (L. V.) subgenus harbor the double-stranded Leishmania RNA virus 1 (LRV-1), previously identified in isolates from Brazil and Peru. Higher levels of LRV-1 in metastasizing strains of L. V. guyanensis have been documented in both human and murine models, and correlated to disease severity.
Expression of proinflammatory biomarkers, including interleukin (IL) 1β, tumor necrosis factor alpha (TNF-α), CXCL10, CCL5, IL-6, and superoxide dismutase, in human macrophages infected with 3 ATCC and 5 clinical isolates of L. V. braziliensis, L. V. guyanensis, and L. V. panamensis for 24 and 48 hours were measured by commercial enzyme immunoassay. Analyses were performed at 24 and 48 hours, stratified by LRV-1 status and species.
LRV-1-positive L. V. braziliensis demonstrated significantly lower expression levels of TNF-α (P = .01), IL-1β (P = .0015), IL-6 (P = .001), and CXCL10 (P = .0004) compared with LRV-1-negative L. V. braziliensis. No differences were observed in strains of L. V. panamensis by LRV-1 status.
Compared to LRV-1-negative L. V. braziliensis, LRV-1-positive strains of L. V. braziliensis produced a predominant Th2-biased immune response, correlated in humans to poorer immunologic control of infection and more severe disease, including mucosal leishmaniasis. Effects of LRV-1 on the pathogenesis of American tegumentary leishmaniasis may be species specific.
维安亚利什曼原虫（L. V.）亚属的物种携带双链利什曼原虫RNA病毒1（LRV-1），该病毒先前在巴西和秘鲁的分离株中被鉴定出来。在圭亚那利什曼原虫转移菌株中，已在人类和小鼠模型中记录到较高水平的LRV-1，且与疾病严重程度相关。
通过商业酶免疫测定法测量感染3株美国典型培养物保藏中心（ATCC）菌株和5株临床分离株的巴西利什曼原虫、圭亚那利什曼原虫和巴拿马利什曼原虫24小时和48小时后的人巨噬细胞中促炎生物标志物的表达，包括白细胞介素（IL）1β、肿瘤坏死因子α（TNF-α）、CXCL10、CCL5、IL-6和超氧化物歧化酶。在24小时和48小时进行分析，按LRV-1状态和物种分层。
与LRV-1阴性的巴西利什曼原虫相比，LRV-1阳性的巴西利什曼原虫显示TNF-α（P = 0.01）、IL-1β（P = 0.0015）、IL-6（P = 0.001）和CXCL10（P = 0.0004）的表达水平显著降低。巴拿马利什曼原虫菌株按LRV-1状态未观察到差异。
与LRV-1阴性的巴西利什曼原虫相比，LRV-1阳性的巴西利什曼原虫产生主要偏向Th2的免疫反应，在人类中与对感染的免疫控制较差和包括黏膜利什曼病在内的更严重疾病相关。LRV-1对美洲皮肤利什曼病发病机制的影响可能具有物种特异性。
