Martynova Ekaterina, Davidyuk Yuriy, Kabwe Emmanuel, Garanina Ekaterina E, Shakirova Venera, Pavelkina Vera, Uskova Yulia, Stott Robert J, Foster Toshana L, Markelova Maria, Goyal Mehendi, Gupta Abhimat, Bhola Mannan, Kumar Vinay, Baranwal Manoj, Rizvanov Albert A, Khaiboullina Svetlana F
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Infectious Diseases Department, Kazan State Medical Academy, 420012 Kazan, Russia.
Pathogens. 2021 Apr 27;10(5):527. doi: 10.3390/pathogens10050527.
Nephropathia Epidemica (NE), endemic to several Volga regions of Russia, including the Republic of Tatarstan (RT) and the Republic of Mordovia (RM), is a mild form of hemorrhagic fever with renal syndrome caused by infection with rodent-borne orthohantaviruses. Although NE cases have been reported for decades, little is known about the hantavirus strains associated with human infection in these regions. There is also limited understanding of the pathogenesis of NE in the RT and the RM. To address these knowledge gaps, we conducted comparative analyses of patients with NE in the RT and the RM. Clinical symptoms were more severe in patients with NE from the RM with longer observed duration of fever symptoms and hospitalization. Analysis of patient sera showed changes in the levels of numerous cytokines, chemokines, and matrix metalloproteases (MMPs) in patients with NE from both the RT and the RM, suggesting leukocyte activation, extracellular matrix degradation, and leukocyte chemotaxis. Interestingly, levels of several cytokines were distinctly different between patients NE from the RT when compared with those from the RM. These differences were not related to the genetic variation of orthohantaviruses circulating in those regions, as sequence analysis showed that Puumala virus (PUUV) was the causative agent of NE in these regions. Additionally, only the "Russia" (RUS) genetic lineage of PUUV was detected in the serum samples of patients with NE from both the RT and the RM. We therefore conclude that differences in serum cytokine, chemokine, and MMP levels between the RT and the RM are related to environmental factors and lifestyle differences that influence individual immune responses to orthohantavirus infection.
流行性肾病（NE）在俄罗斯的几个伏尔加地区流行，包括鞑靼斯坦共和国（RT）和莫尔多瓦共和国（RM），是由啮齿动物传播的正汉坦病毒感染引起的一种轻度出血热伴肾综合征。尽管几十年来一直有NE病例的报告，但对于这些地区与人类感染相关的汉坦病毒株却知之甚少。对RT和RM地区NE发病机制的了解也有限。为了填补这些知识空白，我们对RT和RM地区的NE患者进行了比较分析。来自RM的NE患者临床症状更严重，发热症状和住院观察时间更长。对患者血清的分析表明，来自RT和RM的NE患者体内多种细胞因子、趋化因子和基质金属蛋白酶（MMPs）水平发生了变化，提示白细胞活化、细胞外基质降解和白细胞趋化。有趣的是，与来自RM的NE患者相比，来自RT的NE患者体内几种细胞因子的水平明显不同。这些差异与这些地区流行的正汉坦病毒的基因变异无关，因为序列分析表明普马拉病毒（PUUV）是这些地区NE的病原体。此外，在来自RT和RM的NE患者血清样本中仅检测到PUUV的“俄罗斯”（RUS）基因谱系。因此，我们得出结论，RT和RM地区血清细胞因子、趋化因子和MMP水平的差异与影响个体对正汉坦病毒感染免疫反应的环境因素和生活方式差异有关。
