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Investigation of Human Endogenous Retrovirus-K (ERVK) Expression and Function in Normal Placentation and Preterm Pregnancy

View ORCID ProfileJimi L. Rosenkrantz, View ORCID ProfileMichael Martinez, Adithi Mahankali, View ORCID ProfileLucia Carbone, View ORCID ProfileShawn L. Chavez
doi: https://doi.org/10.1101/2021.11.22.469425
Jimi L. Rosenkrantz
1Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239
2Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR 97006
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  • ORCID record for Jimi L. Rosenkrantz
Michael Martinez
1Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239
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Adithi Mahankali
2Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR 97006
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Lucia Carbone
1Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239
3Division of Genetics, Oregon National Primate Research Center, Beaverton, OR 97006
4Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR 97239
5Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR 97239
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  • For correspondence: chavesh@ohsu.edu carbone@ohsu.edu
Shawn L. Chavez
1Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239
2Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR 97006
6Department of Obstetrics and Gynecology, Oregon Health and Science University School of Medicine, Portland, OR 97239
7Department of Biomedical Engineering, Oregon Health and Science University School of Medicine, Portland, OR 97239
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  • For correspondence: chavesh@ohsu.edu carbone@ohsu.edu
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Abstract

Background There is a growing body of evidence indicating the importance of endogenous retrovirus (ERV) derived proteins during early development and reproduction in mammals. Recently, a protein derived from the youngest ERV in humans, ERVK (HML2), was shown to be expressed during human placentation. Since a number of highly similar ERVK proviral loci exist across the human genome, locus-specific analysis of ERVK transcription and identification of the coding sequence expressed in the human placenta is difficult. Thus, despite its activity in early human development, the native expression and function of ERVK in the human placenta remains largely uncharacterized.

Results In this study, we comprehensively examined locus-specific ERVK transcription across several human placental tissues and cell types. Through a combination of RNA-seq and siRNA knock-down analyses, we identified the expression of a single ERVK locus, ERVK11q23.3, as (1) being significantly upregulated in preterm compared to term placenta, (2) predominantly expressed by mononuclear trophoblasts, (3) capable of encoding a truncated viral-like envelope protein, and (4) contributing to the expression cytokines involved in both antiviral and anti-inflammatory innate immune responses in human placental trophoblasts and BeWo choriocarcinoma cells, respectively.

Conclusions Collectively, the results of this study highlight the utility of studying locus-specific ERVK expression, provide a thorough characterization of locus-specific ERVK transcription from human placental tissues, and indicate that altered expression of placental ERVK11q23.3 influences interferon antiviral response, which may contribute to preterm birth and other pregnancy complications.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted November 22, 2021.
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Investigation of Human Endogenous Retrovirus-K (ERVK) Expression and Function in Normal Placentation and Preterm Pregnancy
Jimi L. Rosenkrantz, Michael Martinez, Adithi Mahankali, Lucia Carbone, Shawn L. Chavez
bioRxiv 2021.11.22.469425; doi: https://doi.org/10.1101/2021.11.22.469425
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Investigation of Human Endogenous Retrovirus-K (ERVK) Expression and Function in Normal Placentation and Preterm Pregnancy
Jimi L. Rosenkrantz, Michael Martinez, Adithi Mahankali, Lucia Carbone, Shawn L. Chavez
bioRxiv 2021.11.22.469425; doi: https://doi.org/10.1101/2021.11.22.469425

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