Receptors in host pathogen interactions between human cytomegalovirus and the placenta during congenital infection

Krishneel Singh; Stuart T Hamilton; Antonia W Shand; Natalie J Hannan; William D Rawlinson

doi:10.1002/rmv.2233

Receptors in host pathogen interactions between human cytomegalovirus and the placenta during congenital infection

Rev Med Virol. 2021 Nov;31(6):e2233. doi: 10.1002/rmv.2233. Epub 2021 Mar 11.

Authors

Krishneel Singh¹, Stuart T Hamilton^{1

2}, Antonia W Shand^{2

3}, Natalie J Hannan^{4

5}, William D Rawlinson^{1

2

6

7}

Affiliations

¹ Serology and Virology Division, NSW Health Pathology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
² School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
³ Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
⁴ Therapeutics Discovery and Vascular Function in Pregnancy Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia.
⁵ Mercy Perinatal, Mercy Hospital for Women Heidelberg, Victoria, Australia.
⁶ School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁷ School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, New South Wales, Australia.

PMID: 33709529
DOI: 10.1002/rmv.2233

Abstract

Cellular receptors in human cytomegalovirus (HCMV) mother to child transmission play an important role in congenital infection. Placental trophoblast cells are a significant cell type in placental development, placental functional processes, and in HCMV transmission. Different cells within the placental floating and chorionic villi present alternate receptors for HCMV cell entry. Syncytiotrophoblasts present neonatal Fc receptors that bind and transport circulating maternal immunoglobulin G across the placental interface which can also be bound to HCMV virions, facilitating viral entry into the placenta and foetal circulation. Cytotrophoblast express HCMV receptors including integrin-α1β1, integrin-αVβ3, epidermal growth factor receptor and platelet-derived growth factor receptor alpha. The latter interacts with HCMV glycoprotein-H, glycoprotein-L and glycoprotein-O (gH/gL/gO) trimers (predominantly in placental fibroblasts) and the gH/gL/pUL128, UL130-UL131A pentameric complex in other placental cell types. The pentameric complex allows viral tropism of placental trophoblasts, endothelial cells, epithelial cells, leukocytes and monocytes. This review outlines HCMV ligands and target receptor proteins in congenital HCMV infection.

Keywords: congenital infection; cytomegalovirus; placenta; pregnancy; receptors.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cytomegalovirus*
Endothelial Cells*
Female
Glycoproteins
Host-Pathogen Interactions*
Humans
Infectious Disease Transmission, Vertical
Placenta / virology*
Pregnancy

Substances

Glycoproteins