In vitro and in vivo protection against enterovirus 71 by an antisense phosphorothioate oligonucleotide

In vitro and in vivo protection against enterovirus 71 by an antisense phosphorothioate... Enterovirus 71 (EV71) is a highly infectious virus that is a major cause of hand, foot, and mouth disease (HFMD), which can lead to severe neurological complications. Currently, there is no effective therapy against EV71. Five antisense oligodeoxynucleotides targeting the 5′-terminal conserved domain of the viral genome were designed using a method based on multiple predicted target mRNA structures. They were then screened for anti-EV71 activity in vitro based on their ability to inhibit an EV71-induced cytopathic effect (CPE). A novel antisense oligonucleotide (EV5) was tested both in rhabdomyosarcoma (RD) cells and in vivo using a mouse model, with a random oligonucleotide (EV5R) of EV5 as a control. EV5 was identified as having significant anti-EV71 activity in vitro and in vivo without significant cytotoxicity. Treatment of RD and Vero cells with antisense oligodeoxynucleotide EV5 significantly and specifically alleviated the cytopathic effect of EV71 in vitro . The inhibitory effect was dose dependent and specific, with a corresponding decrease in viral RNA and viral protein levels. In vivo , EV5 was specifically effective against EV71 virus in preventing death, decreasing weight reduction and reducing the viral RNA copy number and the level of viral proteins in the lungs, intestines and muscles. These results demonstrate the potential and feasibility of using antisense oligodeoxynucleotides specific for the 5′-terminal conserved domain of the viral genome as an antiviral therapy for EV71 disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

In vitro and in vivo protection against enterovirus 71 by an antisense phosphorothioate oligonucleotide

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Publisher
Springer Journals
Copyright
Copyright © 2014 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-014-2054-y
Publisher site
See Article on Publisher Site

Abstract

Enterovirus 71 (EV71) is a highly infectious virus that is a major cause of hand, foot, and mouth disease (HFMD), which can lead to severe neurological complications. Currently, there is no effective therapy against EV71. Five antisense oligodeoxynucleotides targeting the 5′-terminal conserved domain of the viral genome were designed using a method based on multiple predicted target mRNA structures. They were then screened for anti-EV71 activity in vitro based on their ability to inhibit an EV71-induced cytopathic effect (CPE). A novel antisense oligonucleotide (EV5) was tested both in rhabdomyosarcoma (RD) cells and in vivo using a mouse model, with a random oligonucleotide (EV5R) of EV5 as a control. EV5 was identified as having significant anti-EV71 activity in vitro and in vivo without significant cytotoxicity. Treatment of RD and Vero cells with antisense oligodeoxynucleotide EV5 significantly and specifically alleviated the cytopathic effect of EV71 in vitro . The inhibitory effect was dose dependent and specific, with a corresponding decrease in viral RNA and viral protein levels. In vivo , EV5 was specifically effective against EV71 virus in preventing death, decreasing weight reduction and reducing the viral RNA copy number and the level of viral proteins in the lungs, intestines and muscles. These results demonstrate the potential and feasibility of using antisense oligodeoxynucleotides specific for the 5′-terminal conserved domain of the viral genome as an antiviral therapy for EV71 disease.

Journal

Archives of VirologySpringer Journals

Published: Sep 1, 2014

References

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