# Inhibition of cell-to-cell fusion by interferon-induced proteins

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2020 · $234,000

## Abstract

SUMMARY
Interferons (IFNs) are critical products of the immune system that limit the replication of viruses in cells.
However, during pregnancy-associated infections, IFNs can also produce placenta malformation resulting in
fetal demise. While the toxicities of IFNs have been known for decades, the underlying toxic mechanisms are
not known, particularly in the placenta. IFNs induce the production of hundreds of effector proteins, and the
deleterious effects of these individual IFN-induced proteins have been largely unexplored. We have made
significant progress in understanding the IFN-induced transmembrane proteins (IFITMs) and their ability to limit
the severity of virus infections by altering cell membranes to broadly block virus fusion with host cells.
Interestingly, placenta trophoblasts express co-opted retroviral fusion proteins (Syncytin-1 and Syncytin-2) that
allow these cells to fuse with one another to form the syncytiotrophoblast, a placental structure critical for
absorption of oxygen and nutrients at the maternal-fetal interface. Since the fusion of trophoblasts is akin to
virus membrane fusion, we hypothesize that this cell-to-cell fusion reaction can be inhibited by IFNs and
specifically by the anti-fusogenic IFITMs. Our preliminary results indicate that IFITM3 is capable of inhibiting
Syncytin-mediated fusion of heterologous cells and that IFNβ inhibits fusion of a trophoblast cell line and
primary trophoblasts. We will now systematically investigate the effects of IFN subtypes I, II, and III (Aim 1)
and the antiviral IFITMs (IFITM1, 2, and 3) (Aim 2) on Syncytin-mediated fusion in heterologous cells and
human trophoblasts. These studies will provide the missing mechanistic link between IFNs and placenta
toxicity, thus identifying specific molecular targets for mitigating the negative effects of IFNs during pregnancy-
associated infections.

## Key facts

- **NIH application ID:** 9938422
- **Project number:** 5R21AI142256-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jacob Yount
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,000
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938422

## Citation

> US National Institutes of Health, RePORTER application 9938422, Inhibition of cell-to-cell fusion by interferon-induced proteins (5R21AI142256-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9938422. Licensed CC0.

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