A ribozyme derived from the catalytic subunit of RNase P from Escherichia coli is highly effective in inhibiting replication of herpes simplex virus 1.
A sequence-specific ribozyme (M1GS RNA) derived from the catalytic RNA subunit of RNase P from Escherichia coli was used to target the mRNA encoding human herpes simplex virus 1 (HSV-1) major transcription activator, ICP4. A reduction of more than 80% in the expression level of ICP4 and a reduction of about 1000-fold in viral growth were observed in cells that stably expressed the ribozyme. In contrast, a reduction of less than 10 % in ICP4 expression and viral growth was observed in cells that either did not express the ribozyme or produced a catalytically inactive ribozyme mutant. Thus, M1GS ribozyme is highly effective in inhibiting HSV-1 growth and can be used as a general gene-targeting agent for anti-HSV applications.
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Program in Infectious Diseases and Immunity, Program in Comparative Biochemistry School of Public Health, University of California, 140 Warren Hall, Berkeley, CA 94720, USA.
Kilani
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Kim
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Liu
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D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D020134:Catalytic Domain; D002460:Cell Line; D004722:Endoribonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D005814:Genes, Viral / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D043262:Ribonuclease P; D013379:Substrate Specificity; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication
D000998:Antiviral Agents; D029968:Escherichia coli Proteins; D017874:Immediate-Early Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D012367:RNA, Viral; D014157:Transcription Factors; C048925:herpes simplex virus, type 1 protein ICP4; D004722:Endoribonucleases; C468368:RPP14 protein, human; D043262:Ribonuclease P; C470865:ribonuclease P, E coli