# Clinical Implications of HIV-1 Rev-Rev Response Element Functional Activity Variation

> **NIH NIH K08** · UNIVERSITY OF VIRGINIA · 2020 · $191,804

## Abstract

The HIV life cycle requires the export of intron-containing viral mRNAs from the nucleus to the cytoplasm. This
process is ordinarily restricted by the cell, but HIV overcomes this check through the interaction of a viral
protein, Rev, and an RNA secondary structure, the Rev-Response Element (RRE), found on intron-containing
viral transcripts. Variation in the functional activity of the Rev-RRE axis has been observed in viruses taken
from patients infected with HIV, but the clinical significance of that variation and its causal mechanism is not
clearly understood. Previous studies of a related lentivirus clearly show that Rev-RRE activity variation plays a
role in pathogenesis, strongly suggesting that this system is similarly important in HIV infection. It is
hypothesized that the Rev-RRE regulatory axis functions as a rheostat which permits viral adaptation to
different immune environments. In this K08 Mentored Clinical Scientist Research Career Development Award
application, Dr. Patrick Jackson, a fellow in Infectious Diseases at the University of Virginia, proposes to
perform a series of studies to illuminate the role of the Rev-RRE system in HIV transmission and in viral
latency. First, using a novel high-throughput lentiviral vector assay of Rev-RRE functional activity, the role of
this axis in HIV transmission will be examined by comparing Rev-RRE activity in transmitted and circulating
viral quasispecies. Second, the Rev-RRE activity of latent proviruses and circulating viruses will be compared.
High and low activity Rev-RRE pairs will be tested to see if they cause differences in viral replication kinetics
and the production of viral proteins. This phenomenon could underlie the failure of “kick and kill” strategies to
cure HIV. Finally, domain swapping experiments will be performed to identify the sequence determinants of
both Rev and RRE functional activity. Naturally occurring and chimeric Rev and RRE sequences will be utilized
to identify key residues and structures. This research has direct implications for the development of improved
pharmacologic prophylaxis for HIV transmission and for improvements in “kick and kill” HIV cures. This
research will be conducted at the University of Virginia under the mentorship of Drs. David Rekosh and Marie-
Louise Hammarskjold who have a strong track record of training success. Dr. Jackson proposes a career
development plan consisting of experiential learning; formal course work in molecular biology, bioinformatics,
and grant writing; and structured research and professional mentorship. He proposes a specific timeline for
presentation of results at international conferences and in peer reviewed publications, as well as a timeline for
future grant applications. This program is designed to situate him as an independent researcher with expertise
in HIV virology and a skill set which encompasses a broad set of scientific techniques.

## Key facts

- **NIH application ID:** 9820236
- **Project number:** 5K08AI136671-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Patrick Evan Hager Jackson
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,804
- **Award type:** 5
- **Project period:** 2017-12-18 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9820236

## Citation

> US National Institutes of Health, RePORTER application 9820236, Clinical Implications of HIV-1 Rev-Rev Response Element Functional Activity Variation (5K08AI136671-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9820236. Licensed CC0.

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