| Maternal-fetal human immunodeficiency virus type-1 (HIV-1) transmission contributes to the AIDS pandemic. Chemotherapy reduces maternal-fetal HIV-1 transmission, but its impact has been limited to industrialized countries. New intervention approaches require improved understanding of the determinants affecting fetal infection outcomes. We used the feline immunodeficiency virus (FIV) model of maternal-fetal HIV-1 transmission to elucidate basic mechanisms of intrauterine lentivirus infection which are not amenable to study in humans.; Fetuses, placentas, and blood from cats infected with FIV-B-2542 were assayed at defined gestational intervals. Most fetal infections occurred in the third trimester. Fetal tissues frequently targeted by FIV were blood mononuclear cells, brain, and thymus; bone marrow, spleen, and liver were less frequently targeted. Surrogate maternal hematologic and viral load markers did not vary with gestational stage. Therefore, fetal and/or placental factors may determine transmission timing. Infection prevalence in term fetuses was equivalent to that seen in vaginally delivered offspring. Thus, most vertical FIV B-2542 transmission occurs in utero.; Tissues from juvenile cats acutely infected with FIV-B-2542 and FIV-C-Pgmr were used to develop improved immunohistochemistry and DNA in situ hybridization assays. Vines detection was coupled with phenotype labeling to identify specific cells targeted by FIV. Most identified cells containing FIV were T lymphocytes. Macrophages contained virus less commonly. Dendritic cells comprised the smallest percentage of identified FIV+ cells. Bone marrow contained many unidentified FIV+ cells, probably leukocyte progenitors.; Vertical FIV transmission studies were extended to include clades A and C. FIV-A-Petaluma and FIV-C-Pgmr were both transmitted to >60% of term fetuses. FIV-C-Pgmr was detected in all placentas and sampled fetal tissues. FIV-A-Petaluma, by contrast, exhibited little tropism for placenta and was never detected in fetal brain or liver. FIV provirus, but not protein, was detected in placental and fetal tissues in situ, suggesting little active virus replication occurs in these tissues. Fetal tissue FIV sequestration was common. By extension, the blood-based assays used to define the timing of perinatal HIV-1 infection likely underestimate transplacental transmission incidence. Further study of maternal-fetal FIV transmission will shed additional light on the mechanisms of intrauterine HIV-1 transmission. |
