# HIV reverse transcriptase structure, function, inhibition, and roles in viral assembly and maturation

> **NIH AI R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2026 · $770,524

## Abstract

Project Abstract
HIV remains a key health challenge, with fundamental aspects of the viral replication machinery remaining
poorly understood. Building on our extensive studies of HIV-1 reverse transcriptase (RT) structure and
function, we propose to further investigate RT’s roles within the reverse transcription complex (RTC) and the
viral maturation process. Our previous work has provided fundamental insights into HIV-1 RT's molecular
architecture, including key structures of RT complexed with diverse nucleic acid substrates and nucleoside,
non-nucleoside, and other inhibitor types, and has contributed to elucidating molecular mechanisms of
inhibition and resistance. We propose to address three critical knowledge gaps: (1) further definition of the
specific conformational states and transitions during first- and second-strand DNA synthesis initiation and
elongation; (2) the molecular interaction between RT and its partner host protein eEF1A and its functional role
within the RTC; and (3) the role of the RT portion of Gag-Pol in HIV virion assembly and maturation. Using
cutting-edge cryo-EM and X-ray crystallography, complemented by biochemical and virological studies through
established and new collaborations, we will determine structures of RT complexes that capture these dynamic
processes. Our preliminary data include novel structures of RT/DNA:RNA polypurine tract complexes,
successful engineering of polyprotein constructs enabling the visualization of the RT and protease (PR) dimeric
regions within Gag-Pol and Pol polyprotein structures by cryo-EM, and optimization of protein expression and
structure determination for studying the RT-eEF1A interaction. Anticipated outcomes and insights include high-
resolution structures detailing: 1) reverse transcription initiation phases and transition to elongation; 2) RT's
interactions with eEF1A and rationale for its role in promoting reverse transcription; 3) how RT participates in
virion assembly within Pol and Gag-Pol 

## Key facts

- **NIH application ID:** 11408336
- **Project number:** 2R01AI027690-36A1
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** EDWARD  ARNOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $770,524
- **Award type:** 2
- **Project period:** 1988-11-01T00:00:00 → 2031-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11408336

## Citation

> US National Institutes of Health, RePORTER application 11408336, HIV reverse transcriptase structure, function, inhibition, and roles in viral assembly and maturation (2R01AI027690-36A1). Retrieved via AI Analytics 2026-07-21 from https://api.ai-analytics.org/grant/nih/11408336. Licensed CC0.

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