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 immunodeficiency virus (HIV) infection. The incidence of these abnormalities is greater in HIV-infected children when compared with adults, and the patterns of neurological disease are also known to differ from those observed in the adult population. The reasons for these differences are unclear but are most likely related to the immaturity of the host's immune and central nervous systems at the time of infection. This is thought to be particularly true for infants infected with HIV prenatally. To examine these questions, the brains of fetal rhesus macaques that were injected with SIVmac251 at various time points in utero were examined. Direct fetal inoculations were performed on gestational day (GD) 65 (n = 8; early second trimester), GD 110 (n = 4; early third trimester) and GD 130 (n = 2; mid third trimester), with harvest of fetal tissues on GD 80, 100, 130, or 145. Eleven sham controls were included with harvest at correlative time points. Specimens were examined by routine histology, immunohistochemistry, and in situ hybridization to localize vital antigens and SIV nucleic acid. Histologically, scattered glial nodules, spongiosis, and mineralization were found in the basal ganglia and deep white matter in 4 of the 14 fetuses (3 inoculated on GD 65 and one on GD 110). These fetuses and those without histological lesions had vital nucleic acid and SIV antigen in the stroma of the choroid plexus, meninges, and external granular layer of the cerebellum and in columns of cells in the cortical plate. In contrast to juvenile and adult macaques, very few SIV-positive perivascular mononuclear cells were present. These findings suggest that SIV has a different distribution in the brain of fetal macaques after direct infection when compared with adult or juvenile animals. Furthermore, the results of these studies suggest that differences in neurological disease between pediatric and adult patients with acquired immune deficiency syndrome are most likely related to the time of infection.