# Regulatory Crosstalk Between Human Endogenous Retroviruses, HIV, and EBV, in Lymphoma

> **NIH NIH R01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2024 · $1,116,963

## Abstract

PROJECT SUMMARY/ABSTRACT
Approximately 8% of the human genome is composed of sequences directly derived from germline infections of
diverse retroviruses, which have accumulated over the past ~100 million years of mammalian evolution. None
of these human endogenous retroviruses (HERVs) are known to represent fully functional retroviruses, but most
have retained noncoding regulatory sequences that can control expression of cellular genes acting as promoters
or enhancers, and some still encode proteins with various functional activities. While HERV sequences are often
ignored as merely inconsequential ‘junk’ DNA, there is evidence that a subset of these elements play crucial
roles in human physiology and disease, including cancer. Our previous work, as well as that of others, have
shown that both HIV and EBV infections activate certain HERV families that have oncogenic activities, and our
preliminary data reveal an overlap between these elements. Given that diffuse large B cell lymphomas (DBCL)
are frequently associated with EBV infection in people living with HIV, we hypothesize that there is a complex
intercellular regulatory crosstalk between AIDS related (AR)-DLBCL, HIV-infected T cells and the tissue
microenvironment, that is in part mediated by a specific subset of HERVs and their derived products that are
synergistically activated and promote oncogenesis. We will study DLBCL obtained from patients with or without
EBV (and with or without HIV) from the USA and Brazil, which will be comprehensively characterized
pathologically and molecularly using single-cell genomics and spatial transcriptomics. We will analyze these data
using computational tools we have tailored to profile and link HERV and gene expression. Furthermore, we will
establish in vitro models to dissect with precision the functional impact of HERV on the crosstalk between T cells
infected by HIV and B cells with or without EBV. We will also determine if differential HERV expression creates
neoantigenic epitopes, a feature that can be exploited for immunotherapy. This will be accomplished through
three specific aims: 1) Characterize and profile HERV regulation and expression within single cells in DLBCL
and AR-DLBCL; 2) Establish in vitro models to dissect the interaction between cellular and endogenous and
exogenous viruses in AR-DLBCL; 3) Identification of neo-antigenic HERV epitopes in DLBCL and ascertain if
cloned HERV specific CTL can lyse lymphoma cells in vitro. Our team consists of specialists in lymphoma biology
and medicine, transposable elements and HERVs, HIV and EBV viral immunology. Together, we will generate
understandings of how HERVs contribute to the pathogenesis of AR-DLCBL, and identify new antigenic targets
for novel therapies.

## Key facts

- **NIH application ID:** 11143550
- **Project number:** 7R01CA260691-04
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Ethel Cesarman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,116,963
- **Award type:** 7
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11143550

## Citation

> US National Institutes of Health, RePORTER application 11143550, Regulatory Crosstalk Between Human Endogenous Retroviruses, HIV, and EBV, in Lymphoma (7R01CA260691-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11143550. Licensed CC0.

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