# Obesity associated viral pathogenesis

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $388,750

## Abstract

PROJECT SUMMARY
It is estimated that nearly 10% of adults globally are obese and it is a common problem in children. The
incidence of obesity continues to grow in the US and in developing nations. There is an urgent need to
understand how obesity affects immunity to infections. T cells are a principle cell type responsible for
protection against virus infections, and there is evidence from epidemiological studies and in mouse models
that obesity reduces immune protection against infections and vaccine efficacy. Our goal is to use a mouse
model of virus infection to interrogate how adipose tissue and obesity affect T cell responses to infection.
Lymphocytic choriomeningitis virus (LCMV) causes a systemic infection but is resolved within a week by CD8+
T cells. Many of these virus-reactive T cells go on to establish a pool of memory T cells that expedite protection
against re-infection. Recently, we discovered that very large frequencies of virus-specific memory T cells
reside within adipose tissue. These cells are phenotypically and functionally distinct from memory T cells in
lymphoid tissues. Interestingly, diet-induced obesity increased the abundance of these adipose memory T
cells, however, immune obese mice developed severe T cell-mediated pathogenesis upon re-infection. The
pathogenesis included necrosis of adipose and pancreatic tissues, elevated lipase levels, and reduced levels
of circulating calcium. The experiments outlined in this application will allow us to better understand how
obesity and adipose tissue interactions affect T cell memory and immune defenses. In Aim1, we will learn how
memory T cells develop and are maintained in adipose tissue. In Aim2, we investigate how obesity and
adipose cytokines alter memory T cell number, function and distribution. In Aim3, we will determine which T
cell effector function causes lethal outcomes during obesity and whether lipase inhibition or calcium
supplementation can be used to protect against lethality. These efforts will support our long-term goal to better
understand how T cell-adipose tissue interactions worsen outcomes to infection. We plan to eventually
translate these findings into therapies for human subjects with weight disorders.

## Key facts

- **NIH application ID:** 9989034
- **Project number:** 5R01AI138337-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** JASON Kyle WHITMIRE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,750
- **Award type:** 5
- **Project period:** 2018-09-14 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989034

## Citation

> US National Institutes of Health, RePORTER application 9989034, Obesity associated viral pathogenesis (5R01AI138337-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9989034. Licensed CC0.

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