- Title
- Influenza A virus causes maternal and fetal pathology via innate and adaptive vascular inflammation in mice
- Creator
- Liong, Stella; Oseghale, Osezua; To, Eunice; Brassington, Kurt; Erlich, Jonathan; Luong, Raymond; Liong, Felicia; Brooks, Robert; Martin, Cara; O'Toole, Sharon; Vinh, Antony; O'Neill, Luke; Bozinovski, Steven; Vlahos, Ross; Papagianis, Paris; O'Leary, John; Brooks, Doug; Selemidis, Stavros
- Date
- 2020
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/193908
- Identifier
- vital:18268
- Identifier
-
https://doi.org/10.1073/pnas.2006905117
- Identifier
- ISSN:0027-8424 (ISSN)
- Abstract
- Influenza A virus (IAV) infection during pregnancy causes severe maternal and perinatal complications, despite a lack of vertical transmission of IAV across the placenta. Here, we demonstrate a significant alteration in the maternal vascular landscape that underpins the maternal and downstream fetal pathology to IAV infection in mice. In IAV infection of nonpregnant mice, the local lung inflammatory response was contained to the lungs and was self-resolving, whereas in pregnant mice, virus dissemination to major maternal blood vessels, including the aorta, resulted in a peripheral "vascular storm," with elevated proinflammatory and antiviral mediators and the influx of Ly6Clow and Ly6Chigh monocytes, plus neutrophils and T cells. This vascular storm was associated with elevated levels of the adhesion molecules ICAM and VCAM and the pattern-recognition receptors TLR7 and TLR9 in the vascular wall, resulting in profound vascular dysfunction. The sequalae of this IAV-driven vascular storm included placental growth retardation and intrauterine growth restriction, evidence of placental and fetal brain hypoxia, and increased circulating cell free fetal DNA and soluble Flt1. In contrast, IAV infection in nonpregnant mice caused no obvious alterations in endothelial function or vascular inflammation. Therefore, IAV infection during pregnancy drives a significant systemic vascular alteration in pregnant dams, which likely suppresses critical blood flow to the placenta and fetus. This study in mice provides a fundamental mechanistic insight and a paradigm into how an immune response to a respiratory virus, such as IAV, is likely to specifically drive maternal and fetal pathologies during pregnancy. © 2020 National Academy of Sciences. All rights reserved.
- Publisher
- National Academy of Sciences
- Relation
- Proceedings of the National Academy of Sciences of the United States of America Vol. 117, no. 40 (2020), p. 24964-24973
- Rights
- All metadata describing materials held in, or linked to, the repository is freely available under a CC0 licence
- Rights
- https://creativecommons.org/licenses/by/4.0/
- Rights
- Copyright © 2020 National Academy of Sciences
- Rights
- Open Access
- Subject
- MD Multidisciplinary; Inflammation; Influenza; Pregnancy
- Full Text
- Reviewed
- Funder
- This work was supported by the Australian Research Council Future Fellowship Scheme ID FT120100876 (to S.S.) and National Health and Medical Research Council of Australia Project IDs 1122506 and 1128276.
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