Graduate School of Infectious Diseases, Hokkaido University, Sapporo 060-0815, Japan.
Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Viruses. 2022 Oct 13;14(10):2247. doi: 10.3390/v14102247.
Hantaan virus is the causative agent of hemorrhagic fever with renal syndrome (HFRS). The Hantaan virus strain, Korean hemorrhagic fever virus clone-5 (KHF5), causes weight loss and renal hemorrhage in laboratory mice. Clone-4 (KHF4), which has a single E417K amino acid change in its glycoprotein, is an avirulent variant. In this study, KHF4 and KHF5 were compared to evaluate pathological differences in mice in vitro and in vivo. The characteristics of the two glycoproteins were not significantly different in vitro. However, the virulent KHF5 strain targeted the lungs and caused pneumonia and edema in vivo. Both strains induced high infectivity levels in the liver and caused hepatitis; however, petechial hemorrhage and glycogen storage reduction were observed in KHF5-infected mice alone. Renal hemorrhage was observed using viral antigens in the tubular region of KHF5-infected mice. In addition, an increase in white blood cell levels and neutrophilia were found in KHF5-infected mice. Microarray analysis of liver cells showed that CD8+ T cell activation, acute-phase protein production, and neutrophil activation was induced by KHF5 infection. KHF5 infectivity was significantly increased in vivo and the histological and clinicopathological findings were similar to those in patients with HFRS.
汉坦病毒是引起肾综合征出血热（HFRS）的病原体。汉坦病毒株，韩国出血热病毒克隆-5（KHF5），导致实验小鼠体重减轻和肾脏出血。克隆-4（KHF4）在其糖蛋白中有一个单一的 E417K 氨基酸变化，是一种无毒变异体。在这项研究中，比较了 KHF4 和 KHF5，以评估它们在体外和体内对小鼠的病理差异。两种糖蛋白的特征在体外没有显著差异。然而，毒力强的 KHF5 株靶向肺部，导致肺炎和水肿。两种菌株都在肝脏中引起高感染水平，并导致肝炎；然而，只有 KHF5 感染的小鼠才观察到瘀点出血和糖原储存减少。在 KHF5 感染的小鼠中，使用病毒抗原观察到肾小管区域的肾出血。此外，在 KHF5 感染的小鼠中发现白细胞水平升高和中性粒细胞增多。对肝细胞的微阵列分析表明，KHF5 感染诱导 CD8+T 细胞激活、急性期蛋白产生和中性粒细胞激活。KHF5 的感染性在体内显著增加，组织学和临床病理发现与 HFRS 患者相似。
