# Epstein Barr Virus Driven Mechanisms of Post Transplant Lymphoproliferative Disease

> **NIH NIH U01** · STANFORD UNIVERSITY · 2023 · $627,903

## Abstract

PROJECT SUMMARY/ABSTRACT
Epstein Barr virus (EBV) is a broadly disseminated gammaherpes virus that, in immunosuppressed or
immunocompromised individuals, can cause serious, life-threatening B cell lymphomas. In solid organ transplant
(SOT) recipients these EBV+ B cell lymphomas are the most serious manifestation of the group of
heterogeneous lymphoproliferations termed post-transplant lymphoproliferative disease (PTLD). Predisposing
factors for PTLD include primary EBV infection, reactivation of EBV in recipient B cells, and impaired T cell
immunity due to immunosuppression. There are major gaps in our understanding of how specific viral genes
contribute to lymphomagenesis in the context of EBV+ PTLD and whether there are specific alterations in the
immune response to EBV in SOT that develop EBV+ PTLD compared to those that do not. Prior work from our
group has focused on latent membrane protein 1 (LMP1), the major oncogene of EBV, to better understand
EBV+ PTLD pathogenesis. In a recent prospective, multicenter clinical trial in SOT recipients we demonstrated
that specific gain of function mutations in LMP1 significantly correlate with the development of EBV+ PTLD.
We’ve also demonstrated that EBV alters the host cell microRNA profile and that this has direct effects on survival
of EBV+ B lymphoma cells. Building on our previous innovative studies of the bidirectional interactions between
EBV and host immunity, and using our unique Biorepository of samples from SOT recipients that developed
EBV+ PTLD and matched SOT controls that did not develop EBV+ PTLD, we propose to define the impact of
viral genetic diversity on protective immune responses to EBV. We hypothesize that EBV genetic diversity leads
to alterations in viral gene function and immune recognition that contribute to the pathogenesis of EBV+ PTLD.
To test this hypothesis we propose the following Specific Aims:1) Determine the genetic diversity of EBV in PTLD
and the impact on host cell function 2) Determine the effect of EBV+ PTLD-associated genetic diversity on host
immunity to EBV and 3) Determine how extracellular vesicles and microRNA contribute to the development of
EBV+ PTLD. We anticipate these studies will identify novel mechanisms underlying the EBV-driven
pathogenesis of B cell lymphomas in PTLD and will reveal new opportunities for therapeutic strategies to prevent
and treat EBV+ B cell lymphomas in immunosuppressed and immunocompromised individuals.

## Key facts

- **NIH application ID:** 10755055
- **Project number:** 1U01CA275305-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sheri M. Krams
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $627,903
- **Award type:** 1
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10755055

## Citation

> US National Institutes of Health, RePORTER application 10755055, Epstein Barr Virus Driven Mechanisms of Post Transplant Lymphoproliferative Disease (1U01CA275305-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10755055. Licensed CC0.

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