Genetical and biochemical characterizations of hemorrhagic fever with renal syndrome virus infection in mice.

小鼠肾综合征病毒感染出血热的遗传和生化特征。

• 批准号: 03558009
• 负责人: ARIKAWA Jiro
• 金额: $ 9.86万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03558009/
• 关键词: Hemorrhagic fever with renal syndrome; Hantavirus; Animal model; Scid mouse; PCR; Virus infection; Animal experiment; Clinical biochemistry; Scidマウス

1. SCID mice inoculated i.p. with Hantaan virus and Seoul virus developed systemic infection and died after 32 to 38 days post infection.2. Viral antigen was detected from various organs including kidney. Although no hemorrhagic manifestations was seen in kidney, the SCID mice showed increased level of BUN after infection.3. RT-PCR followed by Nested-PCR method was established for detecting Hantaan virus genome in various organs in infected mice.4. SCID mice (21 days post infection) were passively administered with spleen cells which were prepared from normal BALB/c mice. Seven days after the cell transfer, SCID mice began to produce serum antibody to Hantaan virus. In accordance with the appearance of antibody, BUN levels transiently increased. These results suggest the immune response mediated pathology of Hantavirus infection.These results suggest the possible application of SCID mice as the model for hemorrhagic fever with renal syndrome in human. However, the infected SCID mice did not show any hemorrhagic manifestation nor pathologic changes. Further characterizations with the transfer of immune spleen cells and measurement of cytokines in serum will be required.

1.免疫SCID小鼠。结果：1.汉滩病毒和首尔病毒感染后发生全身性感染，感染后32~38天死亡。从包括肾脏在内的各种器官中检测到病毒抗原。SCID小鼠感染后虽然肾脏未见出血表现，但BUN水平明显升高。建立了逆转录聚合酶链式反应-套式聚合酶链式反应检测感染小鼠体内各器官汉滩病毒基因组的方法。用正常BALB/c小鼠制备的脾细胞被动接种SCID小鼠(感染后21d)。细胞转移7天后，SCID小鼠开始产生抗汉滩病毒的血清抗体。随着抗体的出现，BUN水平呈一过性升高。这些结果提示汉坦病毒感染的免疫应答介导的病理机制。这些结果提示SCID小鼠有可能作为人类肾综合征出血热的模型。而感染的SCID小鼠未见任何出血表现和病理改变。免疫脾细胞的转移和血清中细胞因子的测量将需要进一步的特征。

项目成果

Yoo,Y.-C.: "Comparison of virulence between Seoul type virus strain SR-11 and Hantaan type virus strain 76-118 of hantaviruses in suckling mice." Microbiology and Immunology. 37. 557-562 (1993)

Yoo,Y.-C.：“汉坦病毒首尔型病毒株 SR-11 和汉坦型病毒株 76-118 对乳鼠的毒力比较。”

Arikawa, J., Yao, J.-S., Yoshimatsu, K., Takashima, I., Hashimoto, N.: "Protective role of antigenic sites on the envelope protein of Hantaan virus defined by monoclonal antibodies." Archives of Virology. 126. 271-281 (1992)

Arikawa, J.、Yao, J.-S.、Yoshimatsu, K.、Takashima, I.、Hashimoto, N.：“单克隆抗体定义的汉坦病毒包膜蛋白上抗原位点的保护作用。”

Kariwa, H., Arikawa, J., Takashima, I., Isegawa, Y., Yamanishi, K., Hashimoto, N.: "Enhancement of infectivity of hantavirus in cell culture by centrifugation" Journal of Virological Methods. (in press). (1994)

Kariwa, H.、Arikawa, J.、Takashima, I.、Isekawa, Y.、Yamanishi, K.、Hashimoto, N.：“通过离心增强细胞培养物中汉坦病毒的感染性”病毒学方法杂志。

Kobayashi,K.: "Renal lesions in rats intected with Rattus serotype hantavirus(SR-11 strain)." Journal of Veterinary Medicine. B38. 657-664 (1991)

Kobayashi,K.：“感染黄鼠血清型汉坦病毒（SR-11 株）的大鼠的肾脏病变。”

Kariwa,H.: "Develoment and application of protein G antibody assay for the detection of antibody to hantavirus." Journal of Virological Methods. 37. 345-354 (1992)

Kariwa, H.：“用于检测汉坦病毒抗体的 G 蛋白抗体测定的开发和应用。”