Related Experiment Video
Updated: Mar 12, 2026

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
Published on: June 26, 2019
The nucleolar protein GLTSCR2 is required for efficient viral replication
Peng Wang1, Wen Meng1, Shi-Chong Han1
1Key Laboratory of Zoonosis of Ministry of Agriculture, China Agricultural University, Beijing, China.
Abstract:
Glioma tumor suppressor candidate region gene 2 protein (GLTSCR2) is a nucleolar protein. In the investigation of the role of GLTSCR2 that played in the cellular innate immune response to viral infection, we found GLTSCR2 supported viral replication of rhabdovirus, paramyxovirus, and coronavirus in cells. Viral infection induced translocation of GLTSCR2 from nucleus to cytoplasm that enabled GLTSCR2 to attenuate type I interferon IFN-β and support viral replication. Cytoplasmic GLTSCR2 was able to interact with retinoic acid-inducible gene I (RIG-I) and the ubiquitin-specific protease 15 (USP15), and the triple interaction induced USP15 activity to remove K63-linked ubiquitination of RIG-I, leading to attenuation of RIG-I and IFN-β. Blocking cytoplasmic translocation of GLTSCR2, by deletion of its nuclear export sequence (NES), abrogated its ability to attenuate IFN-β and support viral replication. GLTSCR2-mediated attenuation of RIG-I and IFN-β led to alleviation of host cell innate immune response to viral infection. Our findings suggested that GLTSCR2 contributed to efficient viral replication, and GLTSCR2 should be considered as a potential target for therapeutic control of viral infection.
Insights
Glioma tumor suppressor candidate region gene 2 protein (GLTSCR2) aids viral replication by moving to the cytoplasm and weakening the innate immune response. Targeting GLTSCR2 may offer a new strategy for antiviral therapies.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- The nucleolar protein Glioma tumor suppressor candidate region gene 2 protein (GLTSCR2) role in cellular innate immunity was investigated.
- Understanding GLTSCR2's function is crucial for deciphering host-pathogen interactions during viral infections.
Purpose of the Study:
- To elucidate the role of GLTSCR2 in the cellular innate immune response to viral infections.
- To determine how GLTSCR2 influences viral replication and host defense mechanisms.
Main Methods:
- Investigated GLTSCR2's cellular localization changes upon viral infection.
- Examined the interaction of cytoplasmic GLTSCR2 with RIG-I and USP15.
- Assessed the impact of GLTSCR2 translocation inhibition on viral replication and IFN-β production.
Main Results:
- GLTSCR2 supports the replication of rhabdovirus, paramyxovirus, and coronavirus.
- Viral infection induces GLTSCR2 nuclear-to-cytoplasmic translocation, where it interacts with RIG-I and USP15.
- This interaction enhances USP15 activity, leading to RIG-I deubiquitination, reduced type I interferon (IFN-β) production, and consequently, enhanced viral replication.
Conclusions:
- GLTSCR2 attenuates the host's innate immune response by interfering with the RIG-I signaling pathway.
- GLTSCR2 facilitates efficient viral replication, suggesting it as a potential therapeutic target for controlling viral infections.
Related Concept Videos
Leaky Scanning
Subviral Agents
Regulation of Nuclear Protein Sorting
Viral Replication: Lytic Cycle
Retroviruses
RNA Polymerase II Accessory Proteins

