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

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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.