Abstract
Research on human enteroviruses has resulted in the identification of more than 100 enterovirus types, which use more than 10 protein receptors and/or attachment factors required in cell binding and initiation of the replication cycle. Many of these “viral” receptors are overexpressed in cancer cells. Receptor binding and the ability to replicate in specific target cells define the tropism and pathogenesis of enterovirus types, because cellular infection often results in cytolytic response, i.e., disruption of the cells. Viral tropism and cytolytic properties thus make native enteroviruses prime candidates for oncolytic virotherapy. Copy DNA cloning and modification of enterovirus genomes have resulted in the generation of enterovirus vectors with properties that are useful in therapy or in vaccine trials where foreign antigenic epitopes are expressed from or on the surface of the vector virus. The small genome size and compact particle structure, however, set limits to enterovirus genome modifications. This review focuses on the therapeutic use of native and recombinant enteroviruses and the methods that have been applied to modify enterovirus genomes for therapy.
Highlights
Picornaviruses form one of the largest RNA virus groups
This review focuses on the therapeutic use of native and recombinant enteroviruses and the methods that have been applied to modify enterovirus genomes for therapy
The RNA genome functions as mRNA, which is encoded into a large polyprotein via the internal ribosome entry site (IRES) translation mechanism
Summary
Picornaviruses form one of the largest RNA virus groups. At present, the family Picornaviridae contains 26 genera and three proposed genera, which include several important human and animal pathogens causing a range of diseases from infections of the central nervous system to respiratory illnesses [1]. Generation enteroviral most enteroviruses the receptor is not known because experimental studies have gathered around generation of has enteroviral clones has of enabled studies of role virus andinthe cDNA clones enabledcDNA studies virus replication and the ofreplication viral proteins it, role but model enterovirus types. Non-protein factors such as heparan sulphate and sialic acid mediate of viral in it, and and themodified development and use in of gene modified enteroviruses in gene therapy, the proteins development use of enteroviruses therapy, or in oncolytic virotherapy. (pA); (B) Epitope display vectors contain short foreign inserts to display epitopes (in grey) within the structural protein-encoding region; (C,D) Protein expression vectors. Thepolyprotein upstream cistron is formed foreign insert driven by the original IRES, and the viral polyprotein is expressed under the control of the IRES2. There areofbasically two reasons thatIs have limited the modification of enteroviruses: the lack
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