Role of biomolecular condensates in regulating HIV-1 viral ribonucleoprotein complex formation in the setting of substance use disorder
Active Project Grant Awarded Last action
- Award ID
- R33DA053689
- Recipient
-
Pennsylvania State University UEI TNKGNDAWB445
- Awarding agency
-
National Institute on Drug Abuse
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,778,253
Award facts
- Assistance listing
- 93.279 Drug Use and Addiction Research Programs
- Completion date 92% complete
- Originally
- Place of performance
- Hershey, PA 17033, USA
Award details come from USAspending.gov.
Description
- 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $353,173 | |
| Amendment | $355,212 | |
| Amendment | $355,212 | |
| Amendment | $357,328 | |
| Original award | $357,328 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Sir Mortimer B. Davis-Jewish General Hospital | $58,400 | |
| The Sir Mortimer B. Davis-Jewish General Hospital | $59,400 |
Quick answers
Who received award R33DA053689?
R33DA053689 was awarded to Pennsylvania State University by National Institute on Drug Abuse (National Institutes of Health) on May 1, 2021.
How much is award R33DA053689 worth?
$1,778,253 has been obligated on R33DA053689.
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