APOBEC3A is upregulated by human cytomegalovirus (HCMV) in the maternal-fetal interface, acting as an innate anti-HCMV effector

Yiska Weisblum, Esther Oiknine-Djian, Zichria Zakay-Rones, Olesya Vorontsov, Ronit Haimov-Kochman, Yuval Nevo, David Stockheim, Simcha Yagel, Amos Panet, Dana G. Wolf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Human cytomegalovirus (HCMV) is the leading cause of congenital infection and is associated with a wide range of neurodevelopmental disabilities and intrauterine growth restriction. Yet our current understanding of the mechanisms modulating transplacental HCMV transmission is poor. The placenta, given its critical function in protecting the fetus, has evolved effective yet largely uncharacterized innate immune barriers against invading pathogens. Here we show that the intrinsic cellular restriction factor apolipoprotein B editing catalytic subunit-like 3A (APOBEC3A [A3A]) is profoundly upregulated following ex vivo HCMV infection in human decidual tissues- constituting the maternal aspect of the placenta. We directly demonstrated that A3A severely restricted HCMV replication upon controlled overexpression in epithelial cells, acting by a cytidine deamination mechanism to introduce hypermutations into the viral genome. Importantly, we further found that A3 editing of HCMV DNA occurs both ex vivo in HCMV-infected decidual organ cultures and in vivo in amniotic fluid samples obtained during natural congenital infection. Our results reveal a previously unexplored role for A3A as an innate anti-HCMV effector, activated by HCMV infection in the maternal-fetal interface. These findings pave the way to new insights into the potential impact of APOBEC proteins on HCMV pathogenesis.

Original languageEnglish
Article numbere01296-17
JournalJournal of Virology
Volume91
Issue number23
DOIs
StatePublished - 1 Dec 2017

Bibliographical note

Publisher Copyright:
© 2017 American Society for Microbiology.

Keywords

  • Antiviral cellular restrictions
  • APOBEC
  • Congenital infection
  • Decidua
  • HCMV
  • Intrinsic immunity
  • Placental innate immunity
  • Viral placental transmission

Fingerprint

Dive into the research topics of 'APOBEC3A is upregulated by human cytomegalovirus (HCMV) in the maternal-fetal interface, acting as an innate anti-HCMV effector'. Together they form a unique fingerprint.

Cite this