Inhibition of human immunodeficiency virus by using an oligonucleoside methylphosphonate targeted to the tat-3 gene.
Antiviral effects were characterized for two oligodeoxyribonucleoside methylphosphonates synthesized in an antisense (3'-TCTTAACC-5') or a sense (5'-AGAATTGG-3') orientation, based on the RNA sequence of the first splice acceptor site of the tat-3 gene of human immunodeficiency virus (HIV) (5'...AGAAUUGG...3'). The development of syncytial cells and supernatant reverse transcriptase was inhibited by a single exposure to the antisense HIV, and HIV RNA synthesis was inhibited by both antisense and sense methylphosphonates but not by a control herpes simplex virus antisense sequence.
Zaia
J A
JA
City of Hope National Medical Center, Duarte, California.
Rossi
J J
JJ
Murakawa
G J
GJ
Spallone
P A
PA
Stephens
D A
DA
Kaplan
B E
BE
Eritja
R
R
Wallace
R B
RB
Cantin
E M
EM
D000998:Antiviral Agents / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral; D003854:Deoxyribonucleotides / Q000494:pharmacology*; D015696:Gene Products, tat; D005814:Genes, Viral / Q000187:drug effects*; D006678:HIV / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D006801:Humans; D009838:Oligodeoxyribonucleotides; D012367:RNA, Viral / Q000096:biosynthesis / Q000187:drug effects*; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D003854:Deoxyribonucleotides; D015696:Gene Products, tat; D009838:Oligodeoxyribonucleotides; D012367:RNA, Viral; D014157:Transcription Factors; C021992:dideoxyribonucleoside methylphosphonates; D054322:tat Gene Products, Human Immunodeficiency Virus; D012194:RNA-Directed DNA Polymerase