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RNA Helicase DDX3: A Double-Edged Sword for Viral Replication and Immune Signaling
Tomás Hernández-Díaz1,2, Fernando Valiente-Echeverría1,2, Ricardo Soto-Rifo1,2
1Laboratory of Molecular and Cellular Virology, Virology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
Abstract:
DDX3 is a cellular ATP-dependent RNA helicase involved in different aspects of RNA metabolism ranging from transcription to translation and therefore, DDX3 participates in the regulation of key cellular processes including cell cycle progression, apoptosis, cancer and the antiviral immune response leading to type-I interferon production. DDX3 has also been described as an essential cellular factor for the replication of different viruses, including important human threats such HIV-1 or HCV, and different small molecules targeting DDX3 activity have been developed. Indeed, increasing evidence suggests that DDX3 can be considered not only a promising but also a viable target for anticancer and antiviral treatments. In this review, we summarize distinct functional aspects of DDX3 focusing on its participation as a double-edged sword in the host immune response and in the replication cycle of different viruses.
Insights
The DEAD-box helicase 3 (DDX3) protein plays a dual role in the immune response and viral replication. Targeting DDX3 shows promise for developing new anticancer and antiviral therapies.
Area of Science:
- Molecular Biology
- Virology
- Immunology
Background:
- DDX3 is an ATP-dependent RNA helicase crucial for RNA metabolism.
- It regulates key cellular processes like cell cycle, apoptosis, and immune responses.
- DDX3 is essential for the replication of various viruses, including HIV-1 and HCV.
Purpose of the Study:
- To review the multifaceted roles of DDX3.
- To highlight DDX3's function as a 'double-edged sword' in host immunity and viral replication.
- To discuss DDX3 as a therapeutic target for cancer and viral infections.
Main Methods:
- Literature review of studies on DDX3 function.
- Analysis of DDX3's involvement in RNA metabolism.
- Examination of DDX3's role in viral replication and host immune response.
Main Results:
- DDX3 significantly impacts transcription, translation, and cellular processes.
- It acts as both a facilitator and inhibitor in antiviral immunity.
- DDX3 is vital for the life cycle of numerous viruses.
- Small molecules targeting DDX3 have been developed.
Conclusions:
- DDX3 is a critical regulator of cellular functions and viral replication.
- Its complex role in immunity makes it a promising therapeutic target.
- Targeting DDX3 offers potential for novel anticancer and antiviral treatments.
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