BOR - Papers in Press, published online ahead of print
May 12, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.028118
BIOLOGY OF REPRODUCTION 71, 797803 (2004)
DOI: 10.1095/biolreprod.104.028118
© 2004 by the Society for the Study of Reproduction, Inc.
Human Cytomegalovirus-Induced Upregulation of Intercellular Cell Adhesion Molecule-1 on Villous Syncytiotrophoblasts
G. Chan2,3,
M.F. Stinski4, and
L.J. Guilbert1,2,3
The Department of Medical Microbiology and Immunology2
the Perinatal Research Centre,3 University of Alberta, Edmonton, Alberta, Canada T6G 2S2
The Department of Microbiology,4 College of Medicine, University of Iowa, Iowa City, Iowa
Human cytomegalovirus (HCMV) is secreted apically from villous trophoblasts, thus congenital infection is not likely to occur by basal release across the basement membrane. As an alternative route, we hypothesize that an HCMV-infected villous syncytiotrophoblast (ST) upregulates intercellular adhesion molecule (ICAM)-1, causing blood monocytes to bind to the ST and induce apoptosis. Purified (>99.99%) populations of human villous trophoblasts were differentiated into an ST-like culture, infected with HCMV strain AD169, and assessed for ICAM-1 expression by immunofluorescence. Infection strongly upregulated ICAM-1 24 h after challenge. ICAM-1 was also stimulated by transfection with viral genes IE2-55, IE1-72, and IE2-86, but not by UV-inactivated virus. Infection with a green fluorescent protein recombinant virus allowed infection and ICAM-1 expression to be topographically located. We found that ICAM-1 was expressed on both infected and noninfected cells. Furthermore, antibody to tumor necrosis factor (TNF)
and, to a lesser extent, interleukin (IL)1ß inhibited ICAM-1 upregulation on noninfected cells but not on infected cells. We conclude that HCMV IE proteins stimulate ICAM-1 expression on villous trophoblasts by paracrine release of TNF
and IL1ß, as well as by a direct effect on infected cells.
1 Correspondence: Larry J. Guilbert, Department of Medical Microbiology and Immunology, 6-25 HMRC, University of Alberta, Edmonton, Alberta T6G 2S2 Canada. FAX: 780 492 9828; larry.guilbert{at}ualberta.ca
Copyright © 2004 by the Society for the Study of Reproduction.