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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Receptors and Host Factors for Enterovirus Infection: Implications for Cancer Therapy
Olga N Alekseeva1, Le T Hoa2, Pavel O Vorobyev1
1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Abstract:
Enteroviruses, with their diverse clinical manifestations ranging from mild or asymptomatic infections to severe diseases such as poliomyelitis and viral myocarditis, present a public health threat. However, they can also be used as oncolytic agents. This review shows the intricate relationship between enteroviruses and host cell factors. Enteroviruses utilize specific receptors and coreceptors for cell entry that are critical for infection and subsequent viral replication. These receptors, many of which are glycoproteins, facilitate virus binding, capsid destabilization, and internalization into cells, and their expression defines virus tropism towards various types of cells. Since enteroviruses can exploit different receptors, they have high oncolytic potential for personalized cancer therapy, as exemplified by the antitumor activity of certain enterovirus strains including the bioselected non-pathogenic Echovirus type 7/Rigvir, approved for melanoma treatment. Dissecting the roles of individual receptors in the entry of enteroviruses can provide valuable insights into their potential in cancer therapy. This review discusses the application of gene-targeting techniques such as CRISPR/Cas9 technology to investigate the impact of the loss of a particular receptor on the attachment of the virus and its subsequent internalization. It also summarizes the data on their expression in various types of cancer. By understanding how enteroviruses interact with specific cellular receptors, researchers can develop more effective regimens of treatment, offering hope for more targeted and efficient therapeutic strategies.
Insights
Enteroviruses can infect cells using specific receptors, offering potential for oncolytic cancer therapy. Understanding these interactions can lead to targeted treatments for various cancers.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Enteroviruses cause diseases from mild to severe, including poliomyelitis and myocarditis.
- These viruses can also function as oncolytic agents, targeting cancer cells.
- Their interaction with host cell receptors is key to infection and potential therapeutic use.
Purpose of the Study:
- To review the relationship between enteroviruses and host cell factors, focusing on cellular receptors.
- To explore the oncolytic potential of enteroviruses in personalized cancer therapy.
- To discuss the application of gene-targeting techniques in studying viral entry mechanisms.
Main Methods:
- Review of literature on enterovirus-host interactions and cellular receptors.
- Discussion of gene-targeting techniques like CRISPR/Cas9 for receptor function analysis.
- Summary of data on enterovirus receptor expression in various cancers.
Main Results:
- Enteroviruses use specific cell receptors (often glycoproteins) for entry, dictating tropism and replication.
- The ability of enteroviruses to exploit diverse receptors highlights their oncolytic potential.
- Bioselected Echovirus type 7/Rigvir demonstrates antitumor activity and is approved for melanoma treatment.
Conclusions:
- Dissecting enterovirus receptor roles provides insights into their cancer therapy potential.
- Understanding viral entry mechanisms can guide the development of targeted therapeutic strategies.
- Further research into enterovirus-host interactions may yield more effective cancer treatments.
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