Characterization of a maternal–fetal HIV transmission model using pregnant macaques infected with HIV‐2₂₈₇

Abstract

To study mechanisms involved in mother-to-fetus transmission of human immunodeficiency virus (HIV) in utero, we have developed a chronically catheterized pregnant macaque model that permits simultaneous and sequential determination of virus in maternal and fetal blood and amniotic fluid during pregnancy. In this report, we have characterized this model using three groups of pregnant macaques designed to sample: (1) maternal blood, fetal blood, and amniotic fluid (n = 6); (2) maternal blood and amniotic fluid (n = 6); or (3) maternal blood only (n = 2). After inoculation with the highly pathogenic HIV-2(287), all pregnant macaques developed brief but intense viremias followed by precipitous CD4+ T-cell declines within 2-3 weeks. While all the infants born to dams of the three groups were HIV positive, the degree of infection and outcome of HIV infection varied. All infants were shown to be HIV-RNA-positive by reverse transcriptase-polymerase chain reaction (RT-PCR). However, HIV-infected cells were detected only in the blood of those born to dams enrolled in groups 1 and 2: most of these infants progressed to CD4+ T-cell depletion. The infants in group 3 exhibited HIV-RNA in plasma, although neither HIV-infected cells nor CD4+ T-cell depletion was detectable. However, all infants developed HIV-2-specific antibody at various levels by 2 months of age. Together, the data suggest that, while the degree of instrumentation may modulate intensity of virus transmission to fetus, the highly pathogenic HIV-2(287) exhibited a high frequency of virus transmission from the mother to fetus.

HIV in central nervous system and behavioral development

“…A stock was prepared by growing the primary isolate in CD8 cell-depleted, phytohemagglutinin-stimulated macaque peripheral blood mononuclear cells (PBMC) [10,11]. The inoculum was prepared by diluting the stock in complete tissue culture medium.…”

“…Frequency of virus-infected PBMC in blood and tissues was determined by co-culture of macaque PBMC as previously described [10,11]. The presence of virus in culture supernatants was detected using an HIV-2 p27 antigen capture assay kit (Coulter Corp., Hialeah, Florida, USA) according to the manufacturer's instructions.…”

The Brain Retains: Nonhuman Primate Models for Pediatric HIV-1 in the CNS

“…Derivative of SIV mac239, differs from SIV mac239 by 8 AA resulting in more productive infection in monocytes/macrophages. HIV-2 287 [63,100]. Highly pathogenic viral strain developed from culture supernatant of HIV-2 EHO.…”

Four decades of leading‐edge research in the reproductive and developmental sciences: The Infant Primate Research Laboratory at the University of Washington National Primate Research Center

“…A unique chronic catheterization model was developed in the IPRL by Dr. Rodney Ho and colleagues that allowed simultaneous investigation of the time-course of lentivirus infection in the female, and response of the fetus to this infection during pregnancy [Ho et al, 1996; Ho et al, 2001]. This model involved implanting catheters in the fundus of the uterine cavity as well as the femoral vein and artery of pregnant nonhuman primates at 120 days of gestation.…”