Trophoblast Research 8:1-17,1994 VERTICAL TRANSMISSION OF HIV: POSSIBLE MECHANISMS AND PLACENTAL RESPONSES Peter Ebbesen 1, Ferenc Toth 2, George Aboagye-Mathiesen 1, Vladimir Zachar 3, Henrik Hager 1, Niels Norskov-Lauritsenl, Peter Mosborg Petersen 1, Claus Juhl~, Jan Villadsen ~, Milan Zdravkovic x, and Anne Mette Dalsgaard 1Department of Virus and Cancer The Danish Cancer Society 10 Gustav Wieds Vej 8000 Aarhus C, Denmark 2Institute of Microbiology Medical University H4012 Debrecen, Hungary 3Center for Molecular Biology Wayne State University 5047 Gullen Mall, Room 520 Detroit, Michigan 48202 USA INTRODUCTION In his fascinating book published in 1934, Needham tells that in ancient Egypt the placenta was believed to be the seat of the external soul. The greatest care was taken to ensure that it was preserved during the lifetime of the owner, at least in the dynastic families. On ceremonial occasions a standard representing the royal placenta was carried protectively in procession in front of the Pharaoh. Fortunately, today for the unborn child, the placenta represents a shield against vertically transferable dangers. Indeed HIV (human immunodeficiency virus) represents such a threat from an infected mother. The key issue which this survey explores is what defense mechanisms may be at work in preventing transmission of HIV to the fetus. The fact that most fetuses escape infection raises the hope of finding protective measures by first understanding the interrelationship of HIV with the placenta. Worldwide approximately 2 million women are infected with HIV and more than 100,000 children are born each year to infected mothers (Chin, 1990). The reported mother to infant transmission rate varies widely, ranging from 13 to 60 percent (Andiman et al., 1990; Mok et al., 1989; Blanche et al., 1989; Mandelbrot and Henrion, 1991). HIV transmission may occur during pregnancy, at parturition, or after delivery. The relative proportion of mother - to - infant HIV transmission attributable to each of these roots is unknown (Consensus Workshop, Siena, 1992). Vertical transmission has been demonstrated to have taken place as early as week 8 and throughout pregnancy (Sprecher et al., 1986; Jovaisas et al., 1986; Mundy et al., 1987; Maury et al., 1989; Hill