# Mechanisms and Consequences of Reverse Transcription in HIV-1 Cores

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $680,784

## Abstract

Summary
HIV-1 infection results in destruction of T helper cells, leading to immunodeficiency and the
disease known as AIDS. Most currently available antiretroviral drugs target the viral reverse
transcriptase, integrase, and protease enzymes. These medicines are effective but not curative,
and therapy must be adhered to rigorously and permanently. Moreover, HIV-1 constantly evolves
and acquires mutations rendering it resistant to therapies. Therefore, ongoing research is needed
to develop drugs against new viral and cellular targets. Owing to its multiple functions in infection,
the HIV-1 capsid represents an attractive therapeutic target, and potent inhibitors targeting this
structure have shown promising results in clinical trials. The capsid, which is an assembled lattice
composed of a single viral protein, forms a shell around the viral genome and associated proteins
and is essential for efficient reverse transcription, a key early step in HIV-1 infection.
Perturbations to the stability of the capsid result in abortive infection, yet the mechanism by which
the capsid ensures efficient reverse transcription is unknown. This project will fill this gap by
defining the effects of capsid perturbations on HIV-1 reverse transcription in vitro, and vice-versa.
Using native viral cores purified from infectious HIV-1 particles, we will employ cutting-edge
biophysical techniques together with computational and molecular virology approaches to
precisely define the role of the viral capsid in HIV-1 reverse transcription. The project will
accomplish the following goals: (1) define the biochemical requirements for reverse transcription
in HIV-1 cores; (2) define the structural transitions in the core during reverse transcription; (3)
determine the role of capsid pores in nucleotide uptake during reverse transcription; and (4)
precisely define the protein-nucleic acid interactions within the core during specific stages of
reverse transcription. Collectively, this project will yield a greater understanding of capsid function
in HIV-1 infection, thereby informing the mechanism of action of an emerging class of antiviral
drugs.
Relevance
The results of this project will be a greater understanding of the functions of the viral capsid that
are critical for HIV-1 infection. This information will inform the development of capsid-targeting
antiviral drugs and improve the treatment of HIV-infected persons, thereby improving public health
and reducing the spread of HIV-1.

## Key facts

- **NIH application ID:** 10880552
- **Project number:** 5R01AI157843-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Christopher R Aiken
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $680,784
- **Award type:** 5
- **Project period:** 2021-07-20 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880552

## Citation

> US National Institutes of Health, RePORTER application 10880552, Mechanisms and Consequences of Reverse Transcription in HIV-1 Cores (5R01AI157843-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10880552. Licensed CC0.

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