Clinical-immunological analysis of vertical HIV transmission employing a monkey model

采用猴模型进行 HIV 垂直传播的临床免疫学分析

• 批准号: 15591782
• 负责人: HAYAKAWA Satoshi
• 金额: $ 2.18万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591782/
• 关键词: HIV,; vertical transmission; animal model; SHIV; placental barrier; apoptosis; cynomolgus monkeys; coed blood; HIV垂直感染; 新生児免疫不全; 脱落膜大顆粒リンパ球; 転写因子; 天然物

Most of congenital Human immunodeficiency virus (HIV) infection can be prevented by oral Zidovudine administration during pregnancy and elective caesarean section before onset of labor. However it is difficult to control transplacental HIV infection during pregnancy, because the mechanism of intrauterine transmission of HIV is not well clarified. Possible roles of placental barrier for viral infection is proposed though its molecular basis is unknown. In this study, we established a monkey model of congenital Simian Human chimeric immunodeficiency virus (SHIV) infection during pregnancy and examined viral kinetics, localization and histopathological changes.Two pregnant cynomolgus monkeys were inoculated with 200 tissue culture infectious dose 50 (TCID_<50>) of highly pathogenic simian/human immunodeficiency virus, which corresponds to rapid progression of AIDS. One monkey delivered dead fetus on the 14^<th> day after inoculation. We performed caesarean section of another monkey on the 18^<th> day of inoculation. Both fetuses were considered to be SHIV infected, because cord blood samples obtained from both animals contained considerable amounts of HIV RNA. (2.55 X10^4 copies/ml and 9.11 X10^2 copies/ml respectively) PCR revealed positive SHIV RNA and provirus DNA in spleen, thymus, liver and lymph nodes of both fetuses. Microscopic examination revealed positive staining of HIVp24 in placenta, spleen, thymus and lymph nodes of both animals. We established as the first time a monkey model of fluminant AIDS and subsequent intrauterine trasnsplacental HIV infection, which may be applicable for further investigation and development of protective procedures.

大多数先天性人类免疫缺陷病毒（HIV）感染可以通过妊娠期间口服齐多夫定和分娩前选择性剖腹产来预防。然而，由于HIV宫内传播的机制尚不清楚，因此很难控制妊娠期经胎盘感染HIV。胎盘屏障在病毒感染中的作用尚不清楚。在本研究中，我们建立了一个猴先天性嵌合免疫缺陷病毒（Simian Human Chimeric Immunodeficiency Virus，SHIV）妊娠感染的猴模型，并研究了病毒的动力学、定位和组织病理学变化，两只妊娠食蟹猴接种了200组织培养感染剂量50（TCID_<50>）的高致病性猴/人免疫缺陷病毒，这对应于艾滋病的快速进展。1只猴在接种后第14天产下死胎<th>。我们在接种第18天对另一只猴进行了剖腹产<th>。这两个胎儿被认为是SHIV感染，因为从这两个动物获得的脐带血样本含有大量的HIV RNA。(2.55 PCR结果显示，两胎的脾脏、胸腺、肝脏和淋巴结中均检出SHIV RNA和前病毒DNA。显微镜检查显示两只动物的胎盘、脾脏、胸腺和淋巴结中HIVp 24染色阳性。我们首次建立了流行性艾滋病和随后宫内经胎盘感染HIV的猴模型，这可能适用于进一步研究和开发保护程序。

项目成果

The plasma glucose lowering action of tetrandrine in streptozotocin-induced diabetic rats

• DOI: 10.1211/0022357023330
• 发表时间: 2004-05-01
• 期刊: JOURNAL OF PHARMACY AND PHARMACOLOGY
• 影响因子: 3.3
• 作者: Chen, WC;Hayakawa, S;Cheng, JT
• 通讯作者: Cheng, JT

Granulocyte colony stimulation factor(G-CSF) suppresses autologous tumour killing(ATK) activity of the peripheral blood lymphocytes in the patients with ovarian carcinoma

粒细胞集落刺激因子（G-CSF）抑制卵巢癌患者外周血淋巴细胞自体肿瘤杀伤（ATK）活性

• 发表时间: 2004
• 期刊: American Journal of.Reproductive.lmmunology 52
• 作者: Ohta Y;Hayakawa S;KarasakiSuznki M;Sugita K;Komine S;Chishima F;Hatta Y;Seo N;Aleemuzamann S;Yamamoto T
• 通讯作者: Yamamoto T

Mediation of beta-endorphin by the isoflavone puerarin to lower plasma glucose in streptozotocin-induced diabetic rats.

异黄酮葛根素介导β-内啡肽降低链脲佐菌素诱导的糖尿病大鼠的血糖。

• 发表时间: 2004
• 期刊: Planta Medica 70(2)
• 作者: Chen WC;Hayakawa S;Yamamoto T;Su HC;Liu IM;Cheng JT.
• 通讯作者: Cheng JT.

西成田進, 早川 智, 山本樹生: "HIV感染妊婦の管理"産婦人科の実際. 52. 771-776 (2003)

Susumu Nishinarita、Satoshi Hayakawa、Kiyo Yamamoto：“HIV 感染孕妇的管理”妇产科实践 52. 771-776 (2003)。

妊婦のウイルス感染症と母体免疫系

孕妇的病毒感染和母体免疫系统

• 发表时间: 2004
• 期刊: 産科と婦人科 61
• 作者: Koganei-Murabayashi C;Hayakawa S;Shimizu K;Yamamoto T;Aleemuzzaman Sheikhi Nemoto N;早川 智;早川 智
• 通讯作者: 早川 智