TY - JOUR
T1 - Chronic villitis of unknown etiology
T2 - Investigations into viral pathogenesis
AU - Ernst, Linda M.
AU - Bockoven, Crystal
AU - Freedman, Alexa
AU - Wang, Vivien
AU - Pellerite, Matthew
AU - Wylie, Todd N.
AU - Wylie, Kristine M.
N1 - Funding Information:
We thank Haley Gula, Jane Schrimpf and Brandi Herter from the Department of Pediatrics at Washington University and Madeleine Caplan and Kathy Mangold from the Department of Pathology and Laboratory Medicine at NorthShore University HealthSystems for their technical expertise and assistance in generating the data for this work. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS / CTSA Grant # UL1TR002345 from the National Center for Research Resources ( NCRR ), a component of the National Institutes of Health (NIH) , and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH.
Funding Information:
This work was supported by funds from the Department of Pathology and Laboratory Medicine , NorthShore University HealthSystem and by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital. AF was supported by F32HD100076 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development . The funders had no role in study design; data collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Funding Information:
This work was supported by funds from the Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem and by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital. AF was supported by F32HD100076 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The funders had no role in study design; data collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.We thank Haley Gula, Jane Schrimpf and Brandi Herter from the Department of Pediatrics at Washington University and Madeleine Caplan and Kathy Mangold from the Department of Pathology and Laboratory Medicine at NorthShore University HealthSystems for their technical expertise and assistance in generating the data for this work. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Chronic villitis of unknown etiology
KW - Herpesviruses
KW - Placenta
KW - Virome
UR - http://www.scopus.com/inward/record.url?scp=85102392758&partnerID=8YFLogxK
U2 - 10.1016/j.placenta.2021.02.020
DO - 10.1016/j.placenta.2021.02.020
M3 - Article
C2 - 33730616
AN - SCOPUS:85102392758
SN - 0143-4004
VL - 107
SP - 24
EP - 30
JO - Placenta
JF - Placenta
ER -