LOCALIZATION OF SIMIAN IMMUNODEFICIENCY VIRUS NUCLEIC-ACID AND ANTIGEN IN BRAINS OF FETAL MACAQUES INOCULATED IN-UTERO

Neurological dysfunction has been shown to be associated with human im munodeficiency virus (HN) infection. The incidence of these abnormalit ies is greater in HIV-infected children when compared with adults, and the patterns of neurological disease are also known to differ from th ose observed It the adult population, The reasons for these difference s are unclear but are most likely related to the immaturity of the hos t's immune and central nervous systems at the time of infection, This is thought to be particularly true for infants infected with HIV prena tally, To examine these questions, the brains of fetal the sus macaque s that were infected with SIVmac251 at various time points in utero we re examined, Direct fetal inoculations were performed on gestational d ay CGD) 65 (n = 5; early second trimester), GD 110 (n = 4; early third trimester) and GD 130 (n = 2; mid third trimester), with harvest of f etal tissues on GD 80, 100, 130, or 145, Eleven sham controls were inc luded with harvest at correlative time points, Specimens were examined by routine histology, immunohistochemistry, and in situ hybridization to localize viral antigens and SN nucleic acid, histologically, scatt ered glial nodules, spongiosis, and mineralization were found in the b asal ganglia and deep white matter in 4 of the 14 fetuses (3 inoculate d on GD 65 and one on GD 110), These fetuses and those without histolo gical lesions had viral nucleic acid and SIV antigen in the stroma of the choroid plexus, meninges, and external granular layer of the cereb ellum and ill columns of cells in the cortical plate, In contrast to j uvenile and adult macaques, very few SIV-positive perivascular mononuc lear cells were present, These findings suggest that SN has a differen t distribution in the brain of fetal macaques after direct infection w hen compared with adult or juvenile animals, Furthermore, the results of these studies suggest that differences in neurological disease betw een pediatric and adult patients with acquired immune deficiency syndr ome are most likely related to the time of infection.