# Anti-cytomegalovirus Immune Responses in Atherosclerotic Cardiovascular Disease in Persons Living with HIV

> **NIH NIH K23** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $185,220

## Abstract

Project Summary
Persons with HIV (PWH) have an approximate 2-fold higher risk of cardiovascular disease (CVD) compared to
HIV-negative individuals, which is not explained by traditional risk factors and persists despite effective
antiretroviral therapy. Some evidence suggests that cytomegalovirus (CMV), an almost universal co-infection in
many subgroups of PWH, may be linked to increased CVD risk. However, CMV seropositivity alone (i.e., the
presence of anti-CMV antibodies) has been insufficient as a predictor of CVD, potentially due to the greater
importance of cellular immunity in the CMV-CVD pathway. Cardiovascular events are the leading cause of death
in PWH and although CMV is thought to be important, its specific contribution to CVD in PWH is unclear. Current
knowledge on the contribution of CMV to CVD is limited in several ways: 1) Few human studies have assessed
peripheral blood circulating anti-CMV T cells and prevalent atherosclerosis. 2) There is a paucity of data on
whether CMV-specific T cells are present within human atherosclerotic plaque. 3) At present there is not a
reliable animal model to investigate the infiltration of virus-specific T cells into plaque. We have shown that
CD4+ T cells co-expressing the surface markers CX3CR1, GPR56 and CD57 (i.e. `C-G-C') are largely CMV-
specific. We also showed that C-G-C+ CD4+ T cells are increased in the blood of PWH with metabolic disease
and subclinical atherosclerosis. As the chemokine receptor CX3CR1 is highly expressed on CMV-specific T cells
and traffics cells to activated endothelium, we hypothesize that inflated anti-CMV C-G-C+ CD4+ T cells recruited
to inflamed endothelium via CX3CR1 are a major driver of subclinical atherosclerosis in PWH. I am a physician
scientist skilled in immunology and microbial pathogenesis with training in infectious diseases. My tailored career
development plan will advance my skills through experiential, didactic and professional training in: (1) tissue
immunology; (2) atherosclerosis-pathogenesis; (3) clinical and translational research; (4) human-mouse chimera
models; and (5) responsible conduct of research. With a transdisciplinary mentoring panel with expertise in HIV
clinical research, epidemiology, single cell immunology, CVD, and atherosclerosis, I will accomplish the following
aims. In Aim 1, we will test the hypothesis that peripheral C-G-C+ CD4+ T cells are CMV-specific and associated
with subclinical atherosclerosis in PWH. In Aim 2, we will test the hypothesis that plaque-infiltrating C-G-C+ CD4+
T cells are CMV-specific. In Aim 3, we will use a mouse model to test the hypothesis that recruitment of circulating
CMV-specific C-G-C+ CD4+ T cells to inflamed atheroma is CX3CR1-dependent. Completion of these specific
aims will increase our understanding of whether CMV has an important role in CVD in PWH. With the completion
of my career development plan, I will gain expertise in clinical and translational research, vascular biology, and
cutting...

## Key facts

- **NIH application ID:** 10475307
- **Project number:** 5K23HL156759-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Celestine N Wanjalla
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $185,220
- **Award type:** 5
- **Project period:** 2021-08-25 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475307

## Citation

> US National Institutes of Health, RePORTER application 10475307, Anti-cytomegalovirus Immune Responses in Atherosclerotic Cardiovascular Disease in Persons Living with HIV (5K23HL156759-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10475307. Licensed CC0.

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