Receptors and Host Factors for Enterovirus Infection: Implications for Cancer Therapy
Author:
Alekseeva Olga N.1ORCID, Hoa Le T.2, Vorobyev Pavel O.1ORCID, Kochetkov Dmitriy V.1, Gumennaya Yana D.1ORCID, Naberezhnaya Elizaveta R.1, Chuvashov Denis O.1, Ivanov Alexander V.1ORCID, Chumakov Peter M.1ORCID, Lipatova Anastasia V.1
Affiliation:
1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia 2. Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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.
Funder
Russian Science Foundation Ministry of Science and Higher Education of the Russian Federation
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