INHIBITION OF NEUROTROPIC MOUSE RETROVIRUS REPLICATION IN GLIAL-CELLSBY SYNTHETIC OLIGO(2'-O-METHYL) RIBONUCLEOSIDE PHOSPHOROTHIOATES

Synthetic oligo(2'-O-methyl)ribonucleoside phosphorothioate, FS-25, wh ich is complementary to the splicing acceptor site of neurotropic mous e 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 vi ral production of glial cells persistently infected with FrC6 virus. B oth 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 t hese compounds fundamentally inhibit retrovirus production in glial ce lls in the same manner in which they inhibit HIV production, by blocki ng several viral replication pathways including fresh infection, secon d-round infection, and reverse transcription of the viral genome. Our novel neurotropic retrovirus is a useful experimental model for the de velopment of drugs against HIV infection.