# Investigation of ERV-K-env expression and function in placentation

> **NIH NIH F31** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $39,190

## Abstract

PROJECT SUMMARY/ ABSTRACT
Throughout pregnancy, normal placentation is central to prenatal development and the health of both mother
and baby. Placental abnormalities are strongly associated with several common pregnancy complications, such
as preeclampsia and preterm birth, responsible for ~35% of neonatal and 10% pregnancy-related deaths in
women worldwide. Despite some progress in combating these diseases, our understanding of the placental
abnormalities contributing to these complications is still lacking, since many of the basic molecular and cellular
processes underlying normal placentation are not yet fully understood. Recently, there has been a growing
interest in the biological role of endogenous retrovirus (ERV) derived proteins during early development and
placentation. ERVs are endogenous viral elements found in the mammalian genome that closely resemble and
are derived from ancient exogenous retroviruses. While most ERVs within the genome are highly mutated and
lack the ability to express viral genes, some have been shown to contain conserved open reading frames (ORFs)
and encode viral-like proteins. The most notable examples of these in humans are Syncytin-1 and Syncytin-2 in
the placenta, proteins encoded by the envelope (env) gene of ERVs belonging to the ERV-W and ERV-FRD
family, respectively. Syncytins possess fusogenic activity, which is critical during placentation for the normal
formation and maintenance of the outer trophoblast layer at the maternal-fetal interface. Recently, a primate-
specific ERV envelope protein, ERV-K-env, has also been shown to be expressed within trophoblast
subpopulations during normal human placentation. This protein is derived from the ERV-K group, the youngest
and most recently expanded ERV; unlike the Syncytins, ERV-K contains dozens of proviral insertions in the
human genome with predicted intact ORFs. Recent studies using the ERV-K-env consensus sequence identified
fusion (FD) and immunosuppression (ISD) domains closely resembling those found in exogenous
retroviruses, and the inherent ability to elicit fusion and immunosuppression in other cell types. Even though
ERV-K activity during early human development has been the focus of numerous studies, the native expression
and function of ERV-K-env in primate placentation have largely been overlooked. The aims of the proposed
studies are to assess the fusogenic role of ERV-K-env within primate trophoblasts in vitro and to characterize
and elucidate changes in ERV-K-env expression within healthy and pathological placental tissues in vivo. In Aim
1, we will test the hypothesis that ERV-K-env plays a fusogenic role within isolated primate placental trophoblast
cells. For Aim 2, we will test the hypothesis that ERV-K-env expression observed within the healthy placenta is
significantly altered during preterm birth, specifically in a manner that is consistent with reduced ISD and/or FD
function. The ultimate goals of this project are to elucidate the fu...

## Key facts

- **NIH application ID:** 9993984
- **Project number:** 5F31HD094472-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jimi Rosenkrantz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,190
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993984

## Citation

> US National Institutes of Health, RePORTER application 9993984, Investigation of ERV-K-env expression and function in placentation (5F31HD094472-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993984. Licensed CC0.

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