# Role of IFNe in immune modulation and HIV infection

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2022 · $602,815

## Abstract

Project Summary
Interferon e (IFNe) is a critical innate immune mediator that protects the host against sexually transmitted
infections. Although the current paradigm is that IFNε is a type I IFN and signals through IFNa receptors, our
and other published results show that IFNε has unique immune functions that are distinct from IFNa/b. IFNε is
highly abundant in the mucosa of the female reproductive tract, and has superior mucosal immune activity
compared to IFNa/b. IFNe gene expression is regulated by estrogen, cytokines, and seminal plasma, but is not
induced by Toll-like receptor pathways, which induce IFNa/b. Clinical evidence indicates a protective role of
IFNe against HIV. IFNe expression is positively associated with estrogen levels during the menstrual cycle, and
inversely correlates with HIV susceptibility. Importantly, HIV-negative sex workers with frequent exposure to
semen have an increased level of IFNe gene expression, and have increased numbers of immune effector
cells in cervical tissues. We recently demonstrate that IFNe induces an anti-HIV state through a mechanism
independent of known type I IFN-induced HIV host restriction factors in primary macrophages. Additionally,
IFNε elicits a more robust immune response than IFNa2. We hypothesize is that IFNe displays a dual role in
HIV inhibition by protecting HIV target cells and by modulating immune functions, and will test our hypothesis
by determining the immune mechanism of IFNe and its impact on HIV infection in vitro, cervical explants and in
humanized mouse model. To gain a better understanding of the molecular mechanism of IFNe-mediated HIV
inhibition, we determine viral determinants important for IFNe sensitivity. Because estrogen is known to
modulate IFNe expression and mucosal immunity, we will assess the impact of estrogen on IFNε-mediated
processes in HIV infection in postmenopausal women before and after estrogen treatment. Elucidating the
properties and functions of IFNe promises to expand our knowledge of virus-host interactions crucial for HIV
prevention and control of viral reservoirs and immunopathogenesis.

## Key facts

- **NIH application ID:** 10356898
- **Project number:** 5R01AI136948-05
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Theresa L Chang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $602,815
- **Award type:** 5
- **Project period:** 2018-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356898

## Citation

> US National Institutes of Health, RePORTER application 10356898, Role of IFNe in immune modulation and HIV infection (5R01AI136948-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10356898. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*