Related Experiment Video
Updated: Jul 20, 2026

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Antiviral action of the tumor suppressor ARF
María A García1, Manuel Collado, César Muñoz-Fontela
1Centro Nacional de Biotecnología (CNB), Universidad Autónoma de Madrid, Madrid, Spain.
Abstract:
Oncogenic viruses frequently target the pathways controlled by tumor suppressor genes, suggesting an extra function for these proteins as antiviral factors. The control exerted by the tumor suppressor Arf on cellular proliferation is crucial to restrict tumor development; however, a potential contribution of Arf to prevent viral infectivity has remained unexplored. In the present study, we investigated the consequences of loss or increased expression of Arf on viral infection. Our results reveal that ARF expression is induced by interferon and after viral infection. Furthermore, we show that ARF protects against viral infection in a gene dosage-dependent manner, and that this antiviral action is mediated in part by PKR through a mechanism that involves ARF-induced release of PKR from nucleophosmin complexes. Finally, Arf-null mice were hypersensitive to viral infection compared to wild-type mice. Together, our results reveal a novel and unexpected role for the tumor suppressor ARF in viral infection surveillance.
Insights
The tumor suppressor Arf (alternative reading frame) protein, crucial for controlling cell growth, also acts as an antiviral factor. Arf protects against viral infections, and Arf-deficient mice show increased susceptibility to viruses.
Area of Science:
- Molecular biology
- Virology
- Cancer research
Background:
- Tumor suppressor genes are often targeted by oncogenic viruses.
- The tumor suppressor Arf (alternative reading frame) protein regulates cellular proliferation.
- The antiviral role of Arf has not been previously investigated.
Purpose of the Study:
- To investigate the role of Arf in viral infection.
- To determine if Arf expression influences viral infectivity.
Main Methods:
- Studied the effects of Arf gene deletion or overexpression on viral infection.
- Analyzed Arf expression levels following interferon or viral stimulation.
- Investigated the mechanism of Arf's antiviral activity involving PKR and nucleophosmin.
- Compared viral infection susceptibility in Arf-null and wild-type mice.
Main Results:
- Arf expression is upregulated by interferon and viral infection.
- Arf exhibits gene dosage-dependent protection against viral infection.
- Arf's antiviral activity is partly mediated by Protein Kinase R (PKR) through its release from nucleophosmin.
- Arf-null mice display heightened sensitivity to viral infections.
Conclusions:
- The tumor suppressor Arf possesses a previously unrecognized function in antiviral defense.
- Arf plays a significant role in the surveillance and control of viral infections.
- Arf's involvement in antiviral mechanisms highlights a link between cancer suppression and immunity.
Related Concept Videos
Antiviral Nucleoside Inhibitors
Abnormal Proliferation
Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...