Project/Area Number |
15591782
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Nihon University |
Principal Investigator |
HAYAKAWA Satoshi Nihon University, Dept.Infect Dis.Cont, Associate Professor, 医学部, 助教授 (30238084)
|
Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Tatsuo Nihon University, Dept Obstet.Gynecol., Professor, 医学部, 教授 (40167721)
CHISHIMA Fumihisa Nihon University, Dept Obstet.Gynecol., Assistant Professor, 医学部, 講師 (50277414)
ALEEMUZZAMAN Sheikh Nihon University, Dept Pathology, Research fellow, 医学部, 助手 (10277436)
NEMOTO Norimichi Nihon University, Dept Pathology, Professor, 医学部, 教授 (80096875)
HONDA Mitsuo National Inst.Infect., AIDS research Center, Disease Research group director, エイズ研究センター, 第一研究グループ長 (20117378)
|
Project Period (FY) |
2003 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | 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 |
Research Abstract |
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.
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