A checkpoint in the cell cycle progression as a therapeutic target to inhibit HIV replication.
Human immunodeficiency virus (HIV) expression is boosted after T lymphocyte stimulation. It is not known, however, in which phase(s) of the cell cycle HIV is maximally expressed. We demonstrate here that cell activation induces limited HIV expression and that progression to cell proliferation is required for optimal HIV replication. We also show that the G1/S cell cycle transition is a critical checkpoint in this process and that limiting progression at this step with antiproliferative drugs suppresses HIV replication. These results identify a specific phase of the cell cycle progression that is critical for HIV expression and suggest a new discrete target for anti-HIV treatment.
Foli
Andrea
A
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
Maiocchi
Maria Angela
MA
Lisziewicz
Julianna
J
Lori
Franco
F
D019380:Anti-HIV Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology / Q000821:virology*; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D009173:Mycophenolic Acid; D006918:Hydroxyurea