Mother-to-infant transmission of HIV-1: the placenta fights back

The Expression of CXCR4/CXCL12 in First-Trimester Human Trophoblast Cells1

“…Despite the continuous circulation of HIV-1 and HIV-1-infected cells in the mothers during pregnancy, only a few infants are infected in utero, and most of these mother-to-child transmissions of HIV-1 occur during labor. More interestingly, syncytiotrophoblasts, which are in direct contact with the maternal blood, apparently select the transmission of R5 HIV strains (use the CCR5 as a coreceptor), but not X4 HIV strains (use the CXCR4 as a coreceptor), though they express CXCR4 during the pregnancy [18,36,37]. The reasons for the paradoxically low frequency of HIV transmission during pregnancy and selective transplacental transmissions are not fully understood.…”

Villitis of unknown etiology: noninfectious chronic villitis in the placenta

“…One observation attesting to the frequency of intimate contact between maternal CD4-positive T cells and fetal DC-SIGN-positive villous macrophages is the high transmission rate of HIV that has been shown to occur between these 2 cells [38]. Interestingly, this transfer is genetically restricted occurring far more commonly in fetal macrophages expressing high levels of the chemokine receptor CCR5 [39,40]. Recent studies have shown that maternal cells not only enter the placental villi but also the fetus itself [41].…”

Expression of DC-SIGN and DC-SIGNRs in placentas of HIV-positive patients

“…There is a shift in pregnancy towards the production of T-helper 2 (Th2) cytokines, including IL-4 and IL-10, promoted by progesterone. [4] The Th2 cytokines IL-4 and IL-13 play an important role in inducing DC-SIGN expression under specific conditions. [23] However, it has been shown that placentas from non-transmitting women maintain normal type 2 placental cytokines (IL-4, IL-10) whereas transmitting women have placentas that express type 1 cytokines (interferon-gamma, tumour necrosis factor beta).…”

“…[3] Even a single dose of nevirapine, when administered during labour and to an infant after birth, can reduce vertical transmission by 50% because it rapidly crosses the placenta. [3,4] The use of highly active antiretroviral therapy (HAART) throughout pregnancy and prophylactic CS have reduced the rate of vertical transmission in the US to <2%. [5] Infants with a positive HIV polymerase chain reaction (PCR) test within 48 hours of birth are considered to have been infected in utero.…”

“…[2] But even at the highest VLs, only about half of exposed infants become infected with HIV. [2,4] It has been proposed that a breach in the trophoblast layer lining the chorionic villi may result in contact of Hofbauer cells (specialised fetal macrophages) with maternal blood and amniotic fluid. There may also be entry of HIV into the trophoblast layer with subsequent infection of the cell, or the virus could traverse the cells intact, following release at the basolateral surface and exposure to stromal cells.…”