Human cytomegalovirus (HCMV) is the leading cause of congenital infection, associated with severe birth defects.

The most likely transmission route to the fetus is via the placenta, which is injured by HCMV, conceivably contributing to the observed fetal disease. The initial events of maternal-fetal transmission are believed to occur in the maternal decidua.

We have recently established an ex vivo model of HCMV infection in decidual organ cultures, and demonstrated viral spread and broad cellular tropism in the decidual tissue.

Here we employed the decidual infection model to study the tissue immune response to HCMV infection. Using a multiplex 16-cytokine assay, we demonstrated a profound effect of HCMV infection on the decidual immune and angiogenic cytokine/chemokine secretion profile. Significantly, HCMV infection induced decidual INFγ (p=0.03) and IP-10 (p=0.008) secretion at late times post infection.

Up-regulation of INFγ and IP-10 mRNA was demonstrated in the corresponding infected tissues. Importantly, induction of INFγ and IP-10 expression was already observed as early as 6 h post adsorption, and was not dependent on viral gene expression, as revealed by comparable stimulation of INFγ and IP-10 mRNA levels following addition of UV-inactivated virus.

Decidual tissue response to infection was similarly observed with TB40/E and AD169 HCMV strains. Interestingly, this response was unique to the decidual tissue, and was not observed following ex vivo infection of placental tissues obtained from the same donors.

Taken together, these findings reveal a unique and active innate immune response following infection, triggered by sensing a conserved HCMV virion structural component.

The proinflammatory environment induced by HCMV infection in the maternal-fetal interface could adversely affect the outcome of congenital infection.

Authors:

Yiska Weisblum^1,2, Amos Panet², Zichria Zakay-Rones², Ronit Haimov-Kochman³, Debra Goldman-Wohl³, Hagai Amsalem³, Caryn Greenfield³, Esther Djian¹, Shay Tayeb² ,Simcha Yagel³,

Dana G. Wolf¹.

1Clinical Virology Unit

2Department of Biochemistry and the Chanock center for Virology, IMRIC

3Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center & Faculty of Medicine, Jerusalem, Israel.