Inhibition of neurotropic mouse retrovirus replication in glial cells by synthetic oligo(2'-O-methyl)ribonucleoside phosphorothioates.
Synthetic oligo(2'-O-methyl)ribonucleoside phosphorothioate, FS-25, which is complementary to the splicing acceptor site of neurotropic mouse retrovirus (FrC6 virus), and non-complementary analogs including 2'-O-methylinosine homo oligomer (MIS-25), both inhibited viral infection in glial cells. In addition, FS-25 and MIS-25 partially suppressed viral production of glial cells persistently infected with FrC6 virus. Both FS-25 and MIS-25 potently inhibited reverse transcriptase activity of the FrC6 virus in a cell-free system. Addition of these compounds before or after second-round infection of the FrC6 virus inhibited the accumulation of unintegrated viral DNA. These results indicate that these compounds fundamentally inhibit retrovirus production in glial cells in the same manner in which they inhibit HIV production, by blocking several viral replication pathways including fresh infection, second-round infection, and reverse transcription of the viral genome. Our novel neurotropic retrovirus is a useful experimental model for the development of drugs against HIV infection.
Takase-Yoden
S
S
Institute of Life Science, Soka University, Hachioji, Tokyo, Japan.
Shibahara
S
S
Morisawa
H
H
Watanabe
R
R
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D001921:Brain / Q000166:cytology / Q000821:virology*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000187:drug effects; D007292:Inosine Nucleotides / Q000494:pharmacology*; D009052:Leukemia Virus, Murine / Q000187:drug effects* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000821:virology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D012367:RNA, Viral / Q000187:drug effects; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects; D051381:Rats; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D007292:Inosine Nucleotides; D009946:Organothiophosphorus Compounds; D012333:RNA, Messenger; D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase