# Transcription and Replication of Oncogenic Viruses in Hypoxia

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $2,608,181

## Abstract

Summary
Oncogenic viruses are major contributors to approximately 20% of human cancers, with about 8 well-known
viruses directly shown to be causative agents. Our program will focus on examining cellular processes that are
usurped by these viral agents to drive the oncogenic phenotype. The transcription and replication of oncogenic
viruses in the hypoxic microenvironment has not been extensively explored and here we will explore the
mechanisms controlled by Merkel Cell Polyoma Virus (MCPyV), Epstein Barr virus (EBV) and Kaposi’s
Sarcoma Associated Herpesvirus (KSHV). MCPyV is the causative agent of Merkel cell carcinomas, EBV is
the causative agent linked to Nasopharyngeal carcinomas, Burkitt’s lymphomas, Hodgkin’s lymphomas, non-
Hodgkin’s lymphomas, post-transplant lymphoproliferative disease in HIV patients that are
immunocompromised, and KSHV is the causative agent for Kaposi’s sarcoma and pleural effusion lymphomas
and is also associated with Multi-centric Castleman’s disease. These viral agents have been the focus of
decades of studies but their function has not been examined extensively in hypoxia. The focus of this
application is to bring together four prominent groups, led by investigators within the University of Pennsylvania
community to join their scientific expertise to address the mechanism of viral-mediated oncogenesis. The
overall goal will investigate the mechanism of transcription and replication control by viral-encoded antigens
and the metabolic changes that are required for their function in hypoxia. These fundamental cellular
processes targeted in hypoxia will provide novel information for successful establishment of viral infection in
hypoxia.
The program consists of four scientific projects, an administrative core, a virus, vector and cell culture core and
a next generation sequencing core. The scientific projects are: 1. KSHV reprograms transcription and
replication in hypoxia; 2. KSHV induces tumorigenesis by harnessing differentiation in hypoxia; 3. Skin
hypoxia, MCPyV infection and MCC tumorigenesis; and 4. Regulation of EBV latency and oncogenesis by
oxygen metabolism.
The success of these projects will establish a comprehensive mechanistic view of oncogenic viral infection and
pathogenesis in hypoxia, and provide new clues for the development of strategies to prevent and treat the
associated cancers in HIV patients. In addition, the accumulation of new information on the biology of these
viruses will be critical for insights into their mechanism of oncogenesis and so reduce the burden of disease in
HIV infected, transplants and other immunocompromised patients.

## Key facts

- **NIH application ID:** 10914913
- **Project number:** 5P01CA281867-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** ERLE S. ROBERTSON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,608,181
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914913

## Citation

> US National Institutes of Health, RePORTER application 10914913, Transcription and Replication of Oncogenic Viruses in Hypoxia (5P01CA281867-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10914913. Licensed CC0.

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