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. SCID小鼠腹膜内接种汉坦病毒和首尔病毒引起全身感染，感染后32～38天死亡。2．从包括肾脏在内的多个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水平升高。 3．建立了RT-PCR和Nested-PCR检测感染小鼠各器官中汉滩病毒基因组的方法。 4． SCID小鼠（感染后21天）被动给予从正常BALB/c小鼠制备的脾细胞。细胞转移7天后，SCID小鼠开始产生针对汉坦病毒的血清抗体。随着抗体的出现，BUN 水平短暂升高。这些结果表明汉坦病毒感染的免疫反应介导的病理学。这些结果表明SCID小鼠作为人类肾综合征出血热模型的可能应用。然而，感染的SCID小鼠没有表现出任何出血表现或病理变化。需要进一步表征免疫脾细胞的转移和血清中细胞因子的测量。

项目成果

Isegawa,Y.: "Selective amplification of cDNA sequence from total RNA by cassetteligation mediated polymerase chain reaction (PCR):Application to sequencing 6.5kb genome segment of hantavirus strain B-1." Molecular and Cellular Probes. 6. 467-475 (1992)

Isekawa, Y.：“通过盒式连接介导的聚合酶链式反应 (PCR) 从总 RNA 中选择性扩增 cDNA 序列：应用于汉坦病毒株 B-1 的 6.5kb 基因组片段测序。”

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.: "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。”

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。