Universal and mutation-resistant anti-enteroviral activity: potency of small interfering RNA complementary to the conserved cis-acting replication element within the enterovirus coding region.
The promising potential of RNA interference-based antiviral therapies has been well established. However, the antiviral efficacy is largely limited by genomic diversity and genetic instability of various viruses, including human enterovirus B (HEB). In this work, the first evidence supporting the anti-HEB activity of the small interfering RNA (siRNA) targeting the highly conserved cis-acting replication element (CRE) within virus coding region 2C is presented. HeLa cells pre-treated with siRNA complementary to the conserved sequence of the loop region of CRE(2C) were effectively rescued from the cytopathic effects of HEBs. Downregulation of virus replication and attenuation of cytotoxicity were consistently observed in various reference strains and clinical isolates. Cells treated with this siRNA were resistant to the emergence of viable escape mutants and showed sustained antiviral ability. Collectively, the data suggest that the siRNA based on the disordered structure within the highly conserved cis-acting coding region has potential as a universal, persistent anti-HEB agent. The same strategy can be successfully applied to the development of siRNA with consistent antiviral effects in other virus groups possessing similar RNA elements.
Lee
Hui Sun
HS
Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul, Korea.|Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea.
Ahn
Jeonghyun
J
Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul, Korea.|Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea.
Jee
Youngmee
Y
Division of Enteric and Hepatitis Viruses, Department of Virology, National Institute of Health, Korea Center for Disease Control and Prevention, Seoul, Korea.
Seo
Il Sun
IS
Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul, Korea.|Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea.
Jeon
Eun Jung
EJ
Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul, Korea.|Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea.
Jeon
Eun-Seok
ES
Cardiac and Vascular Center, Samsung Medical Center, Seoul, Korea.|Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
Joo
Chul Hyun
CH
Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul, Korea.|Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea.
Kim
Yoo Kyum
YK
Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul, Korea.|Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea.
Lee
Heuiran
H
Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul, Korea.|Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D003588:Cytopathogenic Effect, Viral / Q000235:genetics; D029822:Enterovirus B, Human / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics*; D014709:Vero Cells; D014779:Virus Replication
D034741:RNA, Small Interfering; D012367:RNA, Viral