[Antisense oligonucleotides resistance to coxsackievirus B3 infection in HeLa cells].
OBJECTIVE
Antisense oligodeoxynucleotides (ODNs) hold great promise as therapeutic agents for the treatment of many human diseases. Oligonucleotides specifically hybrid with a selected sequence of RNA or DNA and inhibit the flow of genetic information DNA (or RNA) to proteins. In accordance with the present study, several oligonucleotide sequences that targeted CVB(3) RNA coding Vp(4), Vp(2), Vp(1), cleavage enzyme (P2A) or untranslational region were designed for observation.


METHODS
Antiviral activities of these oligonucleotides were evaluated by plaque reduction assay and cytopathic effect (CPE). Cells were also treated with random oligonucleotides as a specificity control.


RESULTS
Original ODNs, displaying sequence-specific inhibition ranging from 50% to 90% were identified. Three ODNs (at 5 microM concentration), which targeting at the pyrimidine - rich tract (S(CB1)), structural protein VP(1) (S(CB4)) and initiation of translation (S(CB2)) were shown to exhibit inhibition of viral infection 75% to 90% at 1 MOI. There was only low antiviral activity in S(CB5) and S(CB3), and random oligonucleotide were not found having antiviral activity. Oligonucleotides in this study were not toxic at 5 microM concentration.


CONCLUSIONS
A better antiviral antisense oligonucleotides as S(CB1) and S(CB4), S(CB2), could provide candidate antisense oligonucleotides for the treatment of CVB(3) infection.
Sun
H
H
Beijing Central Laboratory of Infection and Immunity, Capital Institute of Pediatrics, Beijing 100020, China.
Liu
Z
Z
Zhang
T
T
D000998:Antiviral Agents / Q000494:pharmacology*; D029822:Enterovirus B, Human / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012367:RNA, Viral / Q000187:drug effects; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D016376:Oligonucleotides, Antisense; D012367:RNA, Viral