# Examining the Role of Chromatin in HIV-1 Integration

> **NIH NIH F31** · MEHARRY MEDICAL COLLEGE · 2020 · $41,163

## Abstract

Project Summary
 The HIV pandemic has infected 72 million people worldwide, and in the US, an estimated 1.2 million
people are currently living with HIV. Despite considerable progress, antiretroviral therapy (ART) remains the
only viable treatment option to curb the disease burden. However, the current ART regimens are toxic, costly,
and face viral resistance; beckoning the need for novel antiretroviral targets. A promising ART target is HIV
integration, the key step for infection. HIV-1 integration targets actively transcribing regions of the host genome
for integrating the viral DNA and establishing infection. Recent reports suggest that the targeting of actively
transcribing genes is associated with clonal expansion and the subsequent viral latency in patients, a primary
barrier for a cure. It is well established that actively transcribing genes are characterized by an “open”
chromatin state, in contrast to a “closed” state indicative of suppressed regions of the genome. Post-
translational modifications (PTM) of the histones define these open and closed regions of the genome, and the
resulting genomic function. In a recent report, HIV-1 hotspots were shown to align with PTM associated with
active transcription. A major question is how HIV targets these open regions of the genome? In cells, HIV
integration is carried out by a nucleoprotein complex of viral DNA and viral/host proteins, called the
preintegration complex (PIC). The viral proteins in the PIC hijack host proteins for the fitness of the HIV
infection. However, PIC function in the context of chromatin, the natural target of HIV-1 integration, and specific
histone PTM is understudied. Our lab has established a protocol to isolate and study intact, naturally forming
PICs. This novel tool allows us to investigate the specific activity of the HIV-1 PIC and define the factors that
are important to integration. The central hypothesis of the proposed studies is that chromatin
characteristic of active transcription increases HIV-1 PIC activity. These studies will address the role of
chromatin in HIV integration by (1) defining the preferred DNA substrate for HIV-1 PIC activity. Then using
biochemical and cellular approaches we will (2) probe the mechanism of integration into chromatin. The
knowledge gained from this investigation will aid in the development of novel drugs against HIV infection.

## Key facts

- **NIH application ID:** 9905313
- **Project number:** 8F31AI150488-02
- **Recipient organization:** MEHARRY MEDICAL COLLEGE
- **Principal Investigator:** Nicklas Ezra Sapp
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $41,163
- **Award type:** 8
- **Project period:** 2019-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9905313

## Citation

> US National Institutes of Health, RePORTER application 9905313, Examining the Role of Chromatin in HIV-1 Integration (8F31AI150488-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9905313. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*