Khaiboullina Svetlana F, Levis Silvana, Morzunov Sergey P, Martynova Ekaterina V, Anokhin Vladimir A, Gusev Oleg A, St Jeor Stephen C, Lombardi Vincent C, Rizvanov Albert A
Nevada Center for Biomedical Research, Reno, NV, USA.
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
Front Immunol. 2017 May 18;8:567. doi: 10.3389/fimmu.2017.00567. eCollection 2017.
Hantavirus infection is an acute zoonosis that clinically manifests in two primary forms, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is endemic in Europe and Russia, where the mild form of the disease is prevalent in the Tatarstan region. HPS is endemic in Argentina, as well as other countries of North and South American. HFRS and HPS are usually acquired via the upper respiratory tract by inhalation of virus-contaminated aerosol. Although the pathogenesis of HFRS and HPS remains largely unknown, postmortem tissue studies have identified endothelial cells as the primary target of infection. Importantly, cell damage due to virus replication, or subsequent tissue repair, has not been documented. Since no single factor has been identified that explains the complexity of HFRS or HPS pathogenesis, it has been suggested that a cytokine storm may play a crucial role in the manifestation of both diseases. In order to identify potential serological markers that distinguish HFRS and HPS, serum samples collected during early and late phases of the disease were analyzed for 48 analytes using multiplex magnetic bead-based assays. Overall, serum cytokine profiles associated with HPS revealed a more pro-inflammatory milieu as compared to HFRS. Furthermore, HPS was strictly characterized by the upregulation of cytokine levels, in contrast to HFRS where cases were distinguished by a dichotomy in serum cytokine levels. The severe form of hantavirus zoonosis, HPS, was characterized by the upregulation of a higher number of cytokines than HFRS (40 vs 21). In general, our analysis indicates that, although HPS and HFRS share many characteristic features, there are distinct cytokine profiles for these diseases. These profiles suggest a strong activation of an innate immune and inflammatory responses are associated with HPS, relative to HFRS, as well as a robust activation of Th1-type immune responses. Finally, the results of our analysis suggest that serum cytokines profiles of HPS and HFRS cases are consistent with the presence of extracellular matrix degradation, increased mononuclear leukocyte proliferation, and transendothelial migration.
汉坦病毒感染是一种急性人畜共患病，临床上主要表现为两种形式，即肾综合征出血热（HFRS）和汉坦病毒肺综合征（HPS）。HFRS在欧洲和俄罗斯流行，在鞑靼斯坦地区该病的轻症形式较为普遍。HPS在阿根廷以及南北美洲的其他国家流行。HFRS和HPS通常是通过吸入被病毒污染的气溶胶经上呼吸道感染。尽管HFRS和HPS的发病机制在很大程度上仍不清楚，但尸检组织研究已确定内皮细胞是主要感染靶点。重要的是，尚未记录到病毒复制或后续组织修复导致的细胞损伤。由于尚未确定单一因素能够解释HFRS或HPS发病机制的复杂性，因此有人提出细胞因子风暴可能在这两种疾病的表现中起关键作用。为了确定区分HFRS和HPS的潜在血清学标志物，使用基于多重磁珠的检测方法对疾病早期和晚期采集的血清样本进行了48种分析物的检测。总体而言，与HFRS相比，与HPS相关的血清细胞因子谱显示出更具促炎环境。此外，HPS的特点是细胞因子水平上调，而HFRS的病例则以血清细胞因子水平的二分法为特征。汉坦病毒人畜共患病的严重形式HPS的特点是上调的细胞因子数量比HFRS多（40种对21种）。总的来说，我们的分析表明，尽管HPS和HFRS有许多共同特征，但这些疾病有不同的细胞因子谱。这些谱表明，相对于HFRS，HPS与先天性免疫和炎症反应的强烈激活以及Th1型免疫反应的强烈激活有关。最后，我们的分析结果表明，HPS和HFRS病例的血清细胞因子谱与细胞外基质降解、单核白细胞增殖增加和跨内皮迁移的存在一致。
