# Age-dependent differences in the immune response to human metapneumovirus

> **NIH NIH F30** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $50,693

## Abstract

ABSTRACT
Human metapneumovirus (HMPV) is a leading cause of lower respiratory infections in young children,
immunocompromised persons, and the elderly, resulting in high morbidity and mortality. Few studies have
investigated why HMPV is more severe in the elderly. This proposal aims to fill this knowledge gap about
HMPV pathogenesis. My preliminary data discovered that aged mice infected with HMPV exhibit delayed viral
clearance, increased lung inflammation, and increased CD8+ HMPV-tetramer+ cells co-expressing the
inhibitory markers PD-1, TIM-3, and LAG-3. I hypothesize that severe HMPV infection in the elderly is
caused by impairment of the CD8+ T cell response. In Aim 1, I will investigate the intrinsic causes of the
CD8+ T cell impairment observed in the aged host infected with HMPV using 10X Multiomics studies on murine
lung directly ex vivo and syngeneic transplants. 10X Multiomics will elucidate age-related epigenetic changes
in CD8+ T cells while syngeneic transplants will transfer young CD8+ T cells into an aged host and vice versa to
determine if CD8+ T cells are the primary immune cells causing the impaired immune response to HMPV (i.e.
increased weight loss, clinical severity, delayed viral clearance). In Aim 2, I will investigate extrinsic causes of
the CD8+ T cell impairment, namely by alveolar macrophages (AMs). I will use a 21-color multispectral flow
cytometry panel to enumerate M1 and M2 macrophage populations in the aged host. In vitro co-culture and
transwell assays of AMs and CD8+ T cells will determine if AMs directly impair CD8+ T cells. Selective depletion
of AMs in aged mice and adoptive transfer of young macrophages will determine how AMs contribute to the
impaired immune response in the aged host. 10X Multiomics will also be performed in this aim to investigate
the age-related epigenetic changes in AMs that may contribute to their aberrant M2 accumulation, which I have
also observed in my preliminary data.
This proposal aims to understand the mechanistic differences in the aged host response to HMPV,
which will help elucidate why HMPV infection in the elderly is more severe. These studies have the potential to
translate into the clinical setting and contribute to better management and treatment for HMPV infection, such
as immunomodulation. Identifying molecular targets in the aged host will guide development of a safe and
effective vaccine against HMPV for all at-risk populations.
In addition, this proposal has tremendous training opportunities, contributing towards my career goals of
becoming a clinician scientist and independent principal investigator in immunology and infectious disease.

## Key facts

- **NIH application ID:** 10896347
- **Project number:** 5F30HL159915-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Olivia Parks
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $50,693
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896347

## Citation

> US National Institutes of Health, RePORTER application 10896347, Age-dependent differences in the immune response to human metapneumovirus (5F30HL159915-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10896347. Licensed CC0.

---

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