# Project 1: Role of HTLV-1 Hbz in Transformation and Disease

> **NIH NIH P01** · OHIO STATE UNIVERSITY · 2022 · $294,128

## Abstract

PROJECT SUMMARY – PROJECT 1
The study of retroviruses has resulted in important discoveries and led to insights into basic cell biology including
mechanisms of cell signaling, regulation of gene expression, and ultimately cellular transformation and cancer.
Our collaborative work within this PPG focuses on HTLV-1, which is associated primarily with adult T-cell
leukemia (ATL) and neurological disease (HAM/TSP) in a small percentage of infected individuals. Disease
progression by HTLV-1 has been attributed to Tax, although we and others have hypothesized and provide data
that another viral gene, termed Hbz, plays a critical role in the malignant process. Our presented data, as well
as the work of others, indicate that hbz is multi-functional, playing important roles in both the RNA and protein
form throughout infection and establishment of latency. We have extended our proposed work through PPG
collaborations to better understand the manner in which hbz promotes proliferative and survival activity in cells.
Proteomic analyses identified a panel of cellular proteins that distinctly interact with hbz RNA and HBZ protein.
Functional characterization of these interactions are the next critical steps and the basis for this highly integrative
continuation project designed to further define the role of hbz in transformation and disease. Our overall
hypothesis is that uncovering the mechanism of actions of hbz RNA and HBZ protein will provide important
insight into HTLV-1 cellular transformation and disease and ultimately will provide means for therapeutic
targeting to eradicate HTLV-1 persistence in the host. This highly integrated proposal as referenced by Project
and Core collaborations below has two Specific Aims. Aim 1 will dissect the mechanism(s) of action of hbz RNA
and determine its contributions to the pathogenic process. We hypothesize that cellular protein interaction with
hbz mRNA 2o structure translates to cell signaling pathways important for viral persistence and cellular
proliferation. Our new proteomics data has identified, and we further validated, distinct cellular proteins that bind
hbz mRNA. This aim will utilize in vitro approaches (Projects 2 and 3, Cores Admin/Biostats and Viral Vector)
to identify the hbz RNA interactive region and determine the functional role of cellular binding proteins in cell
proliferation. We will use in vivo approaches (Animal Core) to understand the contribution of the RNA and
interactive proteins in the establishment of persistence and tumor formation. Aim 2 will dissect the mechanism(s)
of action of HBZ protein and determine its contributions to HTLV-1 pathobiology. Our new proteomics data has
identified, and we further validated, distinct cellular proteins that bind HBZ. In vitro approaches (Project 3, Cores
Admin/Biostats and Viral Vector) including protein interaction mapping, cellular proliferation assays, and
cellular transformation assays will be utilized to identify the HBZ interactive region and...

## Key facts

- **NIH application ID:** 10415186
- **Project number:** 5P01CA100730-18
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Patrick Lee Green
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $294,128
- **Award type:** 5
- **Project period:** 2003-04-21 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415186

## Citation

> US National Institutes of Health, RePORTER application 10415186, Project 1: Role of HTLV-1 Hbz in Transformation and Disease (5P01CA100730-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10415186. Licensed CC0.

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