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利什曼原虫RNA病毒2(LRV2)会加剧由硕大利什曼原虫引起的皮肤损伤,并且对葡甲胺锑酸盐治疗相对无反应。

Leishmania RNA virus 2 (LRV2) exacerbates dermal lesions caused by Leishmania major and comparatively unresponsive to meglumine antimoniate treatment.

作者信息

Saberi Reza, Fakhar Mahdi, Hajjaran Homa, Abbaszadeh Afshar Mohammad Javad, Mohebali Mehdi, Hezarjaribi Hajar Ziaei, Moghadam Yusef, Sharbatkhori Mitra

机构信息

Pediatric Infectious Diseases Research Center, Department of Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Iranian National Registry Center for Lophomoniasis and Toxoplasmosis, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran.

Pediatric Infectious Diseases Research Center, Department of Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Iranian National Registry Center for Lophomoniasis and Toxoplasmosis, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Exp Parasitol. 2022 Oct;241:108340. doi: 10.1016/j.exppara.2022.108340. Epub 2022 Aug 3.

DOI:10.1016/j.exppara.2022.108340
PMID:35932908
Abstract

PURPOSE

The present study investigated the possible role of Leishmania RNA virus 2 (LRV2) in the severity of dermal lesions and treatment failure due to Leishmania major.

METHODS

The drug susceptibility of 14 clinical isolates of L.major, including resistant (n = 7) and sensitive (n = 7) isolates, was checked in the J774A.1 macrophage cell line. The presence of LRV2 among isolates was investigated by the RdRp gene and semi-nested PCR. Moreover, 1 × 10 sensitive L. major LRV2 and LRV2 promastigotes were inoculated subcutaneously into the base tails of the 40 BALB/c mice divided into 4 groups (n = 10 in each group), including clinical LRV2, clinical LRV2, positive control LRV2 and negative control LRV2. The groups were infected with a unique isolate. The lesion size and parasite burden were evaluated.

RESULTS

Sensitive and resistant isolates were determined by the drug susceptibility method. A higher presence of LRV2 was observed among MA-resistant isolates (6/7) compared with susceptible isolates (4/7), which was not statistically significant (P = 0.237). On the other hand, a comparison of the lesion sizes between the LRV2 and LRV2 BALB/c mice groups revealed that the mean size of the lesion in the LRV2 groups was significantly higher than the LRV2 (P = 0.034). In the same direction, there was an increased parasite burden in mice inoculated with LRV2 groups compared with the LRV2- BALB/c mice groups (P = 0.002).

CONCLUSIONS

Our findings showed that the presence of LRV2 could be one of the factors contributing to exacerbating CL. Although we found a higher presence of LRV2 in the resistant isolates, it seems that further investigations are recommended to determine the detailed association between lesions' aggravation and being comparatively unresponsive to treatment.

摘要

目的

本研究调查了利什曼原虫RNA病毒2(LRV2)在重度皮肤病变以及因硕大利什曼原虫导致治疗失败中可能发挥的作用。

方法

在J774A.1巨噬细胞系中检测了14株硕大利什曼原虫临床分离株的药敏情况,其中包括耐药株(n = 7)和敏感株(n = 7)。通过RdRp基因和半巢式PCR检测分离株中LRV2的存在情况。此外,将1×10个敏感的硕大利什曼原虫LRV2和LRV2前鞭毛体分别皮下接种到40只BALB/c小鼠的尾基部,这些小鼠被分为4组(每组n = 10),包括临床LRV2组、临床LRV2组、阳性对照LRV2组和阴性对照LRV2组。各组用单一分离株感染。评估病变大小和寄生虫负荷。

结果

通过药敏方法确定了敏感株和耐药株。与敏感分离株(4/7)相比,在耐米尔托芬分离株(6/7)中观察到LRV2的存在比例更高,但差异无统计学意义(P = 0.237)。另一方面,比较LRV2和LRV2 BALB/c小鼠组之间的病变大小发现,LRV2组的平均病变大小显著高于LRV2组(P = 0.034)。同样,与LRV2 - BALB/c小鼠组相比,接种LRV2组的小鼠体内寄生虫负荷增加(P = 0.002)。

结论

我们的研究结果表明,LRV2的存在可能是导致皮肤利什曼病病情加重的因素之一。虽然我们在耐药分离株中发现LRV2的存在比例更高,但似乎建议进一步研究以确定病变加重与治疗反应相对不敏感之间的详细关联。

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