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Viral infection dampens human fetal membrane type I interferon responses triggered by bacterial LPS

Authors
 Julie A Potter  ;  Mancy Tong  ;  Paulomi Aldo  ;  Ja Young Kwon  ;  Mary Pitruzzello  ;  Gil Mor  ;  Vikki M Abrahams 
Citation
 JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Vol.140 : 103126, 2020-08 
Journal Title
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
ISSN
 0165-0378 
Issue Date
2020-08
Keywords
Bacteria ; Fetal membrane ; Innate immune ; Interferon ; Pregnancy ; Virus
Abstract
The maternal-fetal interface possesses innate immune strategies to protect against infections. We previously reported that prior viral infection of human fetal membranes (FMs) in vitro and mouse FMs in vivo sensitized the tissue to low dose bacterial LPS leading to augmented inflammation. The objective of this study was to examine FM production of type I interferons (IFNs) and IFN-stimulated genes (ISGs) in the context of this polymicrobial model. Human FM explants and pregnant C57BL/6 mice were treated with or without low dose LPS following exposure to media or the γ-herpes virus, MHV-68. FM RNA was analyzed by qRT-PCR for type I IFNs, ISGs, upstream signaling, and MHV-68 open reading frames (ORFs). Pre-exposure to MHV-68 followed by LPS treatment inhibited the ability of LPS to induce human FM type I IFNs (IFNA, IFNB); ISGs (OAS, MxA, APOBEC3G) and upstream signaling mediators (RIG-I, TBK-1). Signaling mediators IRF-3 and IRF-7 were also reduced. In mouse FMs, pre-exposure to MHV-68 followed by LPS treatment reduced the ability of LPS to upregulate Ifna, Ifnb, Mxa, Irf7, and also reduced Irf3. MHV-68 infection of FMs induced ORF45 which targets IRF-7, and this was further augmented in response to a combination of MHV-68 and LPS. Together, these findings indicate that a viral infection blunts FM type I IFN production and signaling in response to LPS leading to a suppressed ISG response. Our studies suggest that a viral infection inhibits this protective FM response by negatively regulating IRF-7 through ORF45, leaving the maternal-fetal interface vulnerable to further viral attack.
Full Text
https://www.sciencedirect.com/science/article/pii/S0165037820300474
DOI
10.1016/j.jri.2020.103126
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Ja Young(권자영) ORCID logo https://orcid.org/0000-0003-3009-6325
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179705
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