Targeting the HIV protein Nef to help the immune system clear HIV
Chemical Biology of HIV-1 Nef
Testing drugs that tag and destroy the HIV protein Nef so the immune system can find and kill infected cells in people living with HIV.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pittsburgh at Pittsburgh NIH-funded |
| Lab location | 1 site (Pittsburgh, United States) |
| Project ID | NIH-11167783 on NIH RePORTER |
What this research studies
This project develops small molecules called PROTACs that bind the HIV protein Nef and force infected cells to degrade it. By removing Nef, these compounds restore MHC-I on the surface of infected T cells so killer T cells can recognize and destroy them. The team tests these molecules in infected immune cells from donors and studies how specifically and effectively they target Nef and block its functions. The aim is to reduce viral rebound and shrink the hidden HIV reservoir that persists despite standard antiretroviral therapy.
Who could benefit from this research
Good fit: People living with HIV—especially those on antiretroviral therapy with suppressed viral loads but persistent latent reservoirs—would be the intended candidates for future trials.
Not a fit: People without HIV and those unable to enroll in clinical trials would not benefit, and because this work is primarily preclinical, direct patient benefit is not guaranteed at this stage.
Why it matters
Potential benefit: If successful, this approach could help the immune system eliminate cells hiding HIV, lower the viral reservoir, and reduce reliance on lifelong antiretroviral therapy.
How similar studies have performed: PROTACs and other targeted protein-degradation approaches have shown promise in laboratory studies and some Nef inhibitors have worked in cell models, but human clinical success has not yet been established.
Where this research is happening
Pittsburgh, United States
- University of Pittsburgh at Pittsburgh — Pittsburgh, United States (Active)
Researchers
- Principal investigator: Smithgall, Thomas E. — University of Pittsburgh at Pittsburgh
- Study coordinator: Smithgall, Thomas E.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.