# Chronic gammaherpesvirus infection and high cholesterol: Adding fuel to the fire

> **NIH NIH R21** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $231,000

## Abstract

ABSTRACT
A large proportion of people worldwide, especially in developed countries, have increased serum
cholesterol levels. In 2012, the CDC estimated that 95 million of adults in U.S. and up to 7% of children
(6-19 years of age) have high total cholesterol levels. Further, a majority of adults in the U.S. (>95%) and
a significant proportion of adolescents carry gammaherpesviruses, cancer-associated pathogens that
establish life-long infection. While it is clear that hypercholesterolemia is frequently accompanied by
increased inflammation and drives cardiovascular disease, it is not clear whether any relationship exists
between elevated cholesterol levels and gammaherpesvirus infection, in spite of the fact that such a
relationship could influence the development of both cardiovascular disease and viral tumorigenesis.
Based on our preliminary data, the proposed studies test the following working model. Genetic variants,
diet, and gammaherpesvirus infection all contribute to elevated circulating levels of lipoprotein-associated
cholesterol (HDL-C and LDL-C; S.A.2). We hypothesize that elevated high density lipoprotein-cholesterol
(HDL-C) has minimal effect on chronic gammaherpesvirus infection and disease (S.A.1 and 3). In contrast,
we propose that elevated LDL-C levels lead to enhanced differentiation of T follicular helper cells (TFH),
boosting the germinal center response and expansion of viral latent reservoir (S.A.1). Further, increased
LDL-C is hypothesized to increase lytic gammaherpesvirus replication directly, via effects on infected cells,
and indirectly, via attenuation of antiviral CD8 T cell response (S.A.1 and 2). Finally, the increased viral
replication is proposed to facilitate the development of atherosclerosis in a host with elevated LDL-C levels
(S.A.3). Successful completion of the proposed experiments will, for the first time, define a physiologically
relevant relationship between ubiquitous chronic gammaherpesvirus infection and hypercholesterolemia,
a relationship that is likely to occur, yet remains unexplored, in a significant proportion of U.S. population
and modify the development of cardiovascular disease and virus-driven cancer. The feasibility of these
proposed multidisciplinary and collaborative studies is supported by the synergism between the distinct,
yet complementary expertise of the two PIs in cholesterol homeostasis and gammaherpesvirus infection.

## Key facts

- **NIH application ID:** 9995154
- **Project number:** 1R21AI147500-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Daisy Sahoo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2020-02-18 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995154

## Citation

> US National Institutes of Health, RePORTER application 9995154, Chronic gammaherpesvirus infection and high cholesterol: Adding fuel to the fire (1R21AI147500-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9995154. Licensed CC0.

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