Linda M Ernst1, Crystal Bockoven2, Alexa Freedman3, Vivien Wang4, Matthew Pellerite5, Todd N Wylie6, Kristine M Wylie6. 1. Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, IL, USA; University of Chicago Pritzker School of Medicine, Chicago, IL, USA. Electronic address: lernst@northshore.org. 2. Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, IL, USA; University of Chicago Pritzker School of Medicine, Chicago, IL, USA. 3. Institute for Policy Research, Northwestern University, Evanston, IL, USA; Department of Obstetrics and Gynecology, NorthShore University HealthSystem, Evanston, IL, USA. 4. Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, IL, USA. 5. Department of Pediatrics, NorthShore University HealthSystem, Evanston, IL, USA. 6. Department of Pediatrics, Washington University, St. Louis, MO, USA.
Abstract
INTRODUCTION: Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of third trimester placenta, which contributes to major adverse obstetric outcomes. However, the inciting factors and mechanisms by which VUE contributes to adverse outcomes are poorly understood. This limits our ability to develop preventions or interventions. Our goals were to determine whether viruses can be detected in placental tissues with VUE and to determine whether gene expression profiles support an antiviral response. METHODS: We extracted RNA and DNA from 20 placentas with high-grade chronic villitis and 20 control placentas without inflammation. Viruses were assessed using ViroCap viral nucleic acid enrichment coupled with metagenomic sequencing. RNA sequencing was used to evaluate the inflammatory gene expression profiles in each placenta. RESULTS: We detected at least 1 virus in 50% of the samples tested. We found that herpesviruses, were found more frequently in cases compared with controls (P = 0.01). Antiviral pathways, including defense response to virus, interferon gamma response, and IFN alpha/beta response, were upregulated in cases. We observed two clusters of gene expression profiles in the VUE cases, suggesting multiple inflammatory profiles are associated with VUE. DISCUSSION: These data support a viral etiology for some cases of VUE. Furthermore, gene expression profiles suggest the possibility of more than one cause or manifestation of VUE. Viral mechanisms should be explored as potential targets for prevention or intervention in VUE.
INTRODUCTION: Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of third trimester placenta, which contributes to major adverse obstetric outcomes. However, the inciting factors and mechanisms by which VUE contributes to adverse outcomes are poorly understood. This limits our ability to develop preventions or interventions. Our goals were to determine whether viruses can be detected in placental tissues with VUE and to determine whether gene expression profiles support an antiviral response. METHODS: We extracted RNA and DNA from 20 placentas with high-grade chronic villitis and 20 control placentas without inflammation. Viruses were assessed using ViroCap viral nucleic acid enrichment coupled with metagenomic sequencing. RNA sequencing was used to evaluate the inflammatory gene expression profiles in each placenta. RESULTS: We detected at least 1 virus in 50% of the samples tested. We found that herpesviruses, were found more frequently in cases compared with controls (P = 0.01). Antiviral pathways, including defense response to virus, interferon gamma response, and IFN alpha/beta response, were upregulated in cases. We observed two clusters of gene expression profiles in the VUE cases, suggesting multiple inflammatory profiles are associated with VUE. DISCUSSION: These data support a viral etiology for some cases of VUE. Furthermore, gene expression profiles suggest the possibility of more than one cause or manifestation of VUE. Viral mechanisms should be explored as potential targets for prevention or intervention in VUE.
Authors: Mi Jeong Kim; Roberto Romero; Chong Jai Kim; Adi L Tarca; Sovantha Chhauy; Christopher LaJeunesse; Deug-Chan Lee; Sorin Draghici; Francesca Gotsch; Juan Pedro Kusanovic; Sonia S Hassan; Jung-Sun Kim Journal: J Immunol Date: 2009-03-15 Impact factor: 5.422
Authors: Alexander Dobin; Carrie A Davis; Felix Schlesinger; Jorg Drenkow; Chris Zaleski; Sonali Jha; Philippe Batut; Mark Chaisson; Thomas R Gingeras Journal: Bioinformatics Date: 2012-10-25 Impact factor: 6.937
Authors: Matthew E Ritchie; Belinda Phipson; Di Wu; Yifang Hu; Charity W Law; Wei Shi; Gordon K Smyth Journal: Nucleic Acids Res Date: 2015-01-20 Impact factor: 16.971
Authors: Maryam Shahi; Ricardo Mamber Czeresnia; E Heidi Cheek; Reade A Quinton; Rana Chakraborty; Elizabeth Ann L Enninga Journal: Front Immunol Date: 2021-07-30 Impact factor: 7.561