# The Effects of Cytomegalovirus on Organ Transplant Rejection

> **NIH NIH F31** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $26,540

## Abstract

Project Summary
Transplant chronic rejection accounts for 30% of patient deaths following cardiac transplantation. The hallmark
lesion of solid-organ allograft chronic rejection (CR) is transplant vascular sclerosis (TVS). TVS is accelerated
by inflammation and immune response at graft sites. Many factors influence the inflammatory immune
environment near a graft to promote chronic rejection. One such factor of particular interest is infection with
Human Cytomegalovirus (HCMV). Because approximately 75% of the human transplant donor/recipient
population is positive for HCMV, the development of novel therapies that mitigate HCMV effects is critical to
treat transplant recipients receiving HCMV+ donor organs to increase graft survival and prevent CR. However,
the viral mechanisms associated with HCMV-acceleration of allograft TVS and CR are poorly understood. A
better understanding of these mechanisms is critical to improving survival and quality of life for transplant
patients.
Current literature suggests that enhancement of the immune response both against the virus and the graft are
leading candidates for early graft destruction and promote viral-acceleration of allograft disease. Host
chemokines promote graft rejection by recruiting and activating immune cells, thereby suggesting that virally
encoded chemokines may also play a role in promoting graft rejection. HCMV is known to modulate the
chemokine axis by inducing chemokine expression following infection, and to encode multiple chemokines and
chemokine receptors, including the chemokines UL128 and UL130. However, the role that these chemokines
play in viral pathogenesis and acceleration of transplant rejection remains poorly understood, and is the focus
of our research. We will investigate these relationships using in vitro assays mimicking a rat cardiac transplant
model with RCMV infection and in vivo studies for cellular infiltrate to cardiac tissue prior to transplantation,
utilizing the RCMV homologue of HCMV UL130, RCMV R131. In particular, we hypothesize that the virally-
encoded CC-chemokine R131 promotes immune cell migration and increases immune cell infiltrate prior to
transplantation, which may lead to inflammation and acceleration of TVS following transplantation in an in vivo
rat cardiac transplantation model. Our second hypothesis is that R131 has a similar role as UL130 in PEC-
mediated entry into macrophages and endothelial cells, which may foster widespread viral dissemination in the
allograft, enhancing graft disease. We will address these hypotheses in Specific Aim 1 by defining post-
translational modifications to R131 and by identifying motifs present within RCMV R131 that mediate migration
in vitro and in vivo. Our goal is to generate a panel of viral mutants that lack chemotactic activity. In Specific Aim
2, we will define the role of R131 in entry into macrophages and endothelial cells and the impacts of R131
mutations in pathogenesis in vivo. In Specific Aim 3, we wi...

## Key facts

- **NIH application ID:** 10020165
- **Project number:** 5F31AI145193-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Iris Katherine Archer Jones
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $26,540
- **Award type:** 5
- **Project period:** 2019-09-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020165

## Citation

> US National Institutes of Health, RePORTER application 10020165, The Effects of Cytomegalovirus on Organ Transplant Rejection (5F31AI145193-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10020165. Licensed CC0.

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