Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA.
Antisense RNA, which has a sequence complementary to mRNA, may provide the basis for antiviral therapies of high selectivity. We have explored the inhibitory effect of six antisense RNAs upon the replication of human immunodeficiency virus (HIV) in cell culture. We chose regions of the HIV genome to test whether sequences required for splicing or for translation initiation were more susceptible to antisense RNA interference. Our results suggest that inhibitory antisense RNAs contain sequences complementary to the AUG initiation codon of the tat gene and have a comparatively low tendency to form intramolecular base pairs which would interfere with intermolecular duplex formation. Inhibition can be substantial (over 70%) but is transient. Transience does not result from mutation of the input virus. Inhibition was not a consequence of the induction of interferon by antisense RNA-mRNA duplex formation. Our results suggest that at least part of the inhibitory effect is at the posttranscriptional level.
Rhodes
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A
Sir William Dunn School of Pathology, University of Oxford, U.K.
James
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W
D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis; D002460:Cell Line; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000235:genetics; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics; D015183:Restriction Mapping; D013539:Simian virus 40 / Q000235:genetics; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014779:Virus Replication
D015704:CD4 Antigens; D016372:RNA, Antisense; D012367:RNA, Viral