Comparative Analysis of In Vitro Models to Study Antibody-Dependent Enhancement of Zika Virus Infection

Thomas Langerak, Noreen Mumtaz, Marion Koopmans, Sam Schoenmakers, Barry Rockx*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

37 Downloads (Pure)

Abstract

During the 2015–2016 outbreak of Zika virus (ZIKV) in the Americas, a previously unknown severe complication of ZIKV infection during pregnancy resulting in birth defects was reported. Since the ZIKV outbreak occurred in regions that were highly endemic for the related dengue virus (DENV), it was speculated that antibody-dependent enhancement (ADE) of a ZIKV infection, caused by the presence of cross-reactive DENV antibodies, could contribute to ZIKV disease severity. Emerging evidence indicates that, while in vitro models can show ADE of ZIKV infection, ADE does not seem to contribute to congenital ZIKV disease severity in humans. However, the role of ADE of ZIKV infection during pregnancy and in vertical ZIKV transmission is not well studied. In this study, we hypothesized that pregnancy may affect the ability of myeloid cells to become infected with ZIKV, potentially through ADE. We first systematically assessed which cell lines and primary cells can be used to study ZIKV ADE in vitro, and we compared the difference in outcomes of (ADE) infection experiments between these cells. Subsequently, we tested the hypothesis that pregnancy may affect the ability of myeloid cells to become infected through ADE, by performing ZIKV ADE assays with primary cells isolated from blood of pregnant women from different trimesters and from age-matched non-pregnant women. We found that ADE of ZIKV infection can be induced in myeloid cell lines U937, THP-1, and K562 as well as in monocyte-derived macrophages from healthy donors. There was no difference in permissiveness for ZIKV infection or ADE potential of ZIKV infection in primary cells of pregnant women compared to non-pregnant women. In conclusion, no increased permissiveness for ZIKV infection and ADE of ZIKV infection was found using in vitro models of primary myeloid cells from pregnant women compared to age-matched non-pregnant women.

Original languageEnglish
Article number2776
JournalViruses
Volume14
Issue number12
DOIs
Publication statusPublished - 13 Dec 2022

Bibliographical note

Funding Information:
This research was funded by [Netherlands Organisation for Health Research and Development] grant number [522003001] and [European Union’s Horizon 2020 Research and Innovation Programme] grant number [734548].

Publisher Copyright:
© 2022 by the authors.

Fingerprint

Dive into the research topics of 'Comparative Analysis of In Vitro Models to Study Antibody-Dependent Enhancement of Zika Virus Infection'. Together they form a unique fingerprint.

Cite this