Human Immunodeficiency Virus Type 1 Causes Productive Infection of Macrophages in Primary Placental Cell Cultures

Abstract

To characterize the role of the placenta in vertical transmission of human immunodeficiency virus type 1 (HIV-1), the susceptibility of primary human placental cultures and of transformed trophoblast cell lines to infection by several HIV-1 isolates was examined. Placental cultures supported the replication of all strains tested, including lymphocyte-, macrophage-, and amphotropic isolates. All viruses replicated to modest levels, with production of both viral antigen and infectious virus in the culture supernatants. Placental cells demonstrated a pattern of permissiveness for HIV-1 isolates distinct from that seen with lymphocytes, blood-derived macrophages, or T cell lines. Immunofluorescent staining showed that 5%-10% of the cultured placental cells expressed viral antigens, and double labeling revealed that the HIV-positive cells were macrophages not trophoblasts. None of the trophoblast cell line (JEG-3, Jar, BeWo, HP-W1) could be infected by HIV. These results support the hypothesis that infection of the placenta could play a role in maternofetal transmission of HIV-1 and suggest that the placental macrophage is likely to be the primary cell type responsible.

The role of trophoblastic microRNAs in placental viral infection

“…Inconsistent results were also observed with HIV and varicella infection of trophoblasts (Douglas et al , 1992; Qureshi et al , 1996). HIV may infect the placenta and, subsequently, the fetus via placental macrophages, but not through trophoblasts, or through breaks in trophoblast integrity (McGann et al , 1994; Burton et al , 1996). Some viruses (HSV, adeno) may infect only less well-differentiated trophoblasts, with decreased infection once the cells differentiate into syncytiotrophoblasts (Parry et al , 1997a; Parry et al , 1997b).…”

Role of placenta in the vertical transmission of human immunodeficiency virus

“…HIV-1 genomic materials have been detected in placental macrophages (Hofbauer cells), cytotrophoblasts and syncytiotrophoblast. [10][11][12] HIV-1 replication and transmission through the placenta may occur through CD4-positive endothelial tissues or CD4-positive Hofbauer cells. Other findings concluded that placental macrophages form a barrier to primary HIV-1.…”

Expression of CD134 and CXCR4 mRNA in term placentas from FIV-infected and control cats

“…In addition, HIV infection of pregnant women often results in poor outcome, including low birth weight babies, pre-term delivery, and an increased incidence of spontaneous abortions (D'Ubaldo et al, 1998;Kumar et al, 1995;Langston et al, 1995). Specific placental cell populations are permissive to productive HIV infection, probably contributing to transplacental transfer of virus or virus-infected cells across the placenta leading to fetal infection (David et al, 1992;McGann et al, 1994;Al-Harthi et al, 2002;Arias et al, 2003) . Although HIV infection clearly has the potential to negatively impact fetal and neonatal health, the mechanism and timing of HIV vertical transmission to the fetus is not yet clear.…”