title: Modeling of human cytomegalovirus maternal-fetal transmission in a novel decidual organ culture.
abstract: Human cytomegalovirus (HCMV) is the leading cause of congenital infection, associated with severe birth defects and intrauterine growth retardation. The mechanism of HCMV transmission via the maternal-fetal interface is largely unknown, and there are no animal models for HCMV. The initial stages of infection are believed to occur in the maternal decidua. Here we employed a novel decidual organ culture, using both clinically derived and laboratory-derived viral strains, for the ex vivo modeling of HCMV transmission in the maternal-fetal interface. Viral spread in the tissue was demonstrated by the progression of infected-cell foci, with a 1.3- to 2-log increase in HCMV DNA and RNA levels between days 2 and 9 postinfection, the expression of immediate-early and late proteins, the appearance of typical histopathological features of natural infection, and dose-dependent inhibition of infection by ganciclovir and acyclovir. HCMV infected a wide range of cells in the decidua, including invasive cytotrophoblasts, macrophages, and endothelial, decidual, and dendritic cells. Cell-to-cell viral spread was revealed by focal extension of infected-cell clusters, inability to recover infectious extracellular virus, and high relative proportions (88 to 93%) of cell-associated viral DNA. Intriguingly, neutralizing HCMV hyperimmune globulins exhibited inhibitory activity against viral spread in the decidua even when added at 24 h postinfection-providing a mechanistic basis for their clinical use in prenatal prevention. The ex vivo-infected decidual cultures offer unique insight into patterns of viral tropism and spread, defining initial stages of congenital HCMV transmission, and can facilitate evaluation of the effects of new antiviral interventions within the maternal-fetal interface milieu.
authors: Clinical Virology Unit, Department of Biochemistry and the Chanock Center for Virology, IMRIC, Jerusalem, Israel.
authors: Yiska
authors: Y
authors: Weisblum
authors: Amos
authors: A
authors: Panet
authors: Zichria
authors: Z
authors: Zakay-Rones
authors: Ronit
authors: R
authors: Haimov-Kochman
authors: Debra
authors: D
authors: Goldman-Wohl
authors: Ilana
authors: I
authors: Ariel
authors: Haya
authors: H
authors: Falk
authors: Shira
authors: S
authors: Natanson-Yaron
authors: Miri D
authors: MD
authors: Goldberg
authors: Ronit
authors: R
authors: Gilad
authors: Nell S
authors: NS
authors: Lurain
authors: Caryn
authors: C
authors: Greenfield
authors: Simcha
authors: S
authors: Yagel
authors: Dana G
authors: DG
authors: Wolf
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000635:transmission*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D003656:Decidua / Q000821:virology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008954:Models, Biological; D009924:Organ Culture Techniques / Q000379:methods; D011247:Pregnancy; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D013997:Time Factors; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D012367:RNA, Viral; D014764:Viral Proteins