凯泰拉正布尼亚病毒的特性及抗凯泰拉正布尼亚病毒感染性疾病治疗候选药物的评估。

Characterization of Keterah orthonairovirus and evaluation of therapeutic candidates against Keterah orthonairovirus infectious disease.

作者信息

Sugimoto Satoko, Suda Yuto, Nagata Noriyo, Fukushi Shuetsu, Yoshikawa Tomoki, Kurosu Takeshi, Mizutani Tetsuya, Saijo Masayuki, Shimojima Masayuki

机构信息

Research and Education Center for Prevention of Global Infectious Disease of Animal, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-0054, Japan; Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-0054, Japan; Department of Virology I, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.

Department of Virology I, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan; Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

出版信息

Ticks Tick Borne Dis. 2022 Jan;13(1):101834. doi: 10.1016/j.ttbdis.2021.101834. Epub 2021 Oct 8.

DOI:10.1016/j.ttbdis.2021.101834

PMID:34656945

Abstract

The species Keterah orthonairovirus is a member of the genus Orthonairovirus. Few studies have focused on this species, and there remains no treatment for Issyk-Kul fever, an infectious disease caused by a Keterah orthonairovirus. This study was performed to characterize this species using two viruses, Issyk-Kul virus (ISKV) and Soft tick bunyavirus (STBV), in cell culture and type I interferon receptor knockout (IFNAR-/-) mice and to evaluate the efficacy of serum transfusion using a mouse model of ISKV infection. The two viruses replicated in many kinds of mammal- and tick-derived cell lines but showed few different characteristics in tropism and antigenicity against anti-viral sera in cell culture. Neither virus caused clinical signs in wild-type mice, but both caused lethal infection in IFNAR-/- mice. ISKV caused more acute death than STBV in IFNAR-/- mice. In both viral infections in IFNAR-/- mice, macroscopic abnormalities were prominent in the liver. Similar levels of viral genome between ISKV- and STBV-infected IFNAR-/- mice were observed in blood, liver, lymphoid tissues and adrenal gland at moribund stages. Hematologic abnormalities in IFNAR-/- mice infected with these viruses, including leukopenia and thrombocytopenia, and biochemical abnormalities indicating liver damage were prominent. In addition, blood levels of many kinds of cytokines and chemokines such as granulocyte colony-stimulating factor, interleukin-6, tumor necrosis factor-α, interferon gamma-induced protein 10 and monocyte chemoattractant protein-1 were elevated. ISKV-immunized serum transfusion after infection delayed the time to death of IFNAR-/- mice. Thus, the present study showed that the species Keterah orthonairovirus could proliferate in most mammal-derived cell lines and cause severe liver lesions and death in IFNAR-/- mice and that serum transfusion might be effective in treatment against Issyk-Kul fever.

摘要

凯特拉正布尼亚病毒是正布尼亚病毒属的一个成员。很少有研究关注这个物种，对于由凯特拉正布尼亚病毒引起的伊塞克湖热，目前仍然没有治疗方法。本研究旨在利用伊塞克湖病毒（ISKV）和软蜱布尼亚病毒（STBV）这两种病毒，在细胞培养以及I型干扰素受体敲除（IFNAR-/-）小鼠中对该物种进行特性分析，并使用ISKV感染的小鼠模型评估血清输血的疗效。这两种病毒能在多种源自哺乳动物和蜱的细胞系中复制，但在细胞培养中，它们在嗜性和对抗病毒血清的抗原性方面几乎没有表现出不同特征。这两种病毒在野生型小鼠中均未引起临床症状，但在IFNAR-/-小鼠中均导致致命感染。在IFNAR-/-小鼠中，ISKV比STBV导致更急性的死亡。在IFNAR-/-小鼠的这两种病毒感染中，肝脏的宏观异常都很突出。在濒死阶段，在血液、肝脏、淋巴组织和肾上腺中观察到，ISKV感染和STBV感染的IFNAR-/-小鼠的病毒基因组水平相似。感染这些病毒的IFNAR-/-小鼠出现血液学异常，包括白细胞减少和血小板减少，以及表明肝脏损伤的生化异常都很突出。此外，多种细胞因子和趋化因子的血液水平升高，如粒细胞集落刺激因子、白细胞介素-6、肿瘤坏死因子-α、干扰素γ诱导蛋白10和单核细胞趋化蛋白-1。感染后输注ISKV免疫血清可延迟IFNAR-/-小鼠的死亡时间。因此，本研究表明，凯特拉正布尼亚病毒物种可在大多数源自哺乳动物的细胞系中增殖，并在IFNAR-/-小鼠中引起严重的肝脏病变和死亡，血清输血可能对治疗伊塞克湖热有效。