Antiviral action of oligodeoxyguanylic acids against human immunodeficiency virus type 1.
Deoxyguanylic acids, but not other deoxynucleotides, as short as 3- to 4-mer, were effective in preventing HIV-1-induced cytopathicity. In addition, they prevented giant cell formation of infected Sup-T1 cells, and p24 production in HIV-1 infected H9 cells. Phosphorylation at either the 5'- or 3'-end enhanced these activities. Furthermore, 5'-phosphorylated phosphorothioate tetradeoxyguanylic acid was effective in reducing HIV production in chronically infected cells (H9/IIIB). The search for the target steps of this compound revealed that it inhibits at least 3 steps in the life cycle of HIV: interaction with CD4 (measured by inhibitory effect on the syncytia formation between Sup-T1 and H9/IIIB cells), reverse transcriptase, and step(s) after integration. These results suggest that phosphorylated phosphorothioate tetradeoxyguanylic acid may be a novel candidate for a therapeutic agent of AIDS.
Fujihashi
T
T
Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Sakata
T
T
Kaji
A
A
Kaji
H
H
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016655:HIV Core Protein p24; D009838:Oligodeoxyribonucleotides; D018894:Reverse Transcriptase Inhibitors; C033538:oligodeoxyguanylic acid; D054303:HIV Reverse Transcriptase