# Role of biomolecular condensates in regulating HIV-1 viral ribonucleoprotein complex formation in the setting of substance use disorder

> **NIH NIH R21** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2022 · $171,878

## Abstract

Abstract
 HIV-1/AIDS is a devastating immunodeficiency disease that has resulted in over 35 million deaths
across the globe. There is a compelling ongoing need to develop novel treatment strategies to combat the
continuing emergence of drug-resistant viral strains. A drug target that has not yet been successfully brought to
the clinic is the interaction of the Gag protein with its RNA genome to form the viral ribonucleoprotein complex,
which initiates the process of virion assembly. A deeper understanding of the biochemical and biophysical
interactions that drive viral ribonucleoprotein complex formation is needed to advance further therapeutic
development. Based on recent findings that viral ribonucleoprotein complexes undergo liquid-liquid phase
separation to form biomolecular condensates, this proposal explores the molecular underpinnings of Gag-viral
RNA interactions. We have assembled an accomplished interdisciplinary team of scientists to work at the
crossroads of retrovirology, RNA biology, biophysics, and pharmacology to shed light on our understanding of
viral and cellular biomolecular condensates in HIV-1 infection.
 Our preliminary results suggesting that HIV-1 ribonucleoprotein complexes form in the nucleus inspired
this provocative proposal to investigate the interplay of virus replication machinery with nuclear bodies that
form biomolecular condensates. In the R21 phase, we will use innovative methods involving biophysics,
genetics, state-of-the-art live cell imaging, and targeted pharmacological interventions to examine whether
HIV-1 ribonucleoprotein complexes assemble into biomolecular condensates in the nucleus. In the R33 phase,
we will extend these studies to probe mechanistic questions focusing on whether nuclear BMCs play critical
roles in regulating HIV-1 transcription, latency reactivation, and genomic RNA packaging. Due to the high
incidence of substance use disorder in people with HIV-1/AIDS, we will also investigate whether drugs of
abuse influence HIV-1 nuclear biomolecular condensates. Elucidating the genetic determinants of HIV-1
condensate formation could lead to the identification of novel drug targets to treat HIV/AIDS.

## Key facts

- **NIH application ID:** 10398171
- **Project number:** 5R21DA053689-02
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Leslie J Parent
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $171,878
- **Award type:** 5
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10398171

## Citation

> US National Institutes of Health, RePORTER application 10398171, Role of biomolecular condensates in regulating HIV-1 viral ribonucleoprotein complex formation in the setting of substance use disorder (5R21DA053689-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10398171. Licensed CC0.

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