The cellular SFPQ protein as a positive factor in the HIV-1 integration
Тatiana Kikhai1, Yulia Agapkina2, Maria Silkina1
1Chemistry Department, Lomonosov Moscow State University, Moscow, Russia.
Biochimie
|February 19, 2024
Summary
The cellular SFPQ protein positively regulates HIV-1 DNA integration by directly interacting with HIV-1 integrase (IN). Disrupting this interaction prevents viral integration, suggesting the SFPQ/IN complex as a therapeutic target.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- The cellular SFPQ protein plays a role in the HIV-1 life cycle, but its precise function remains unclear.
- Understanding SFPQ's role is crucial for developing novel HIV-1 replication inhibitors.
Purpose of the Study:
- To elucidate the mechanism by which SFPQ influences early-stage HIV-1 replication.
- To investigate the interaction between SFPQ and HIV-1 integrase (IN).
Main Methods:
- Studied the effect of intracellular SFPQ levels on HIV-1 DNA integration and reverse transcription.
- Identified and mutated diRGGX1-4 motifs in SFPQ responsible for IN binding.
- Analyzed the impact of SFPQ mutants on viral replication and integration.
Main Results:
- SFPQ levels affect HIV-1 DNA integration but not reverse transcription, indicating SFPQ is a positive factor for integration.
- Two diRGGX1-4 motifs in SFPQ's N-terminal region are critical for IN binding; mutations impair this interaction.
- SFPQ mutants unable to bind IN failed to affect viral integration, confirming direct interaction is key.
Conclusions:
- SFPQ facilitates HIV-1 integration through direct interaction with HIV-1 integrase.
- The SFPQ/IN complex represents a promising therapeutic target for new HIV-1 replication inhibitors.
