Adenine-induced selective apoptosis toward HIV chronically infected cells in vitro.
A novel strategy for anti-HIV therapy is the clearance of the residual infected cells from the body. Here, we show that 6-aminopurine, adenine, induced selective apoptosis toward HIV-1 producing chronically infected MOLT4 cells (MOLT4/HIV) without augmentation of virus production, whereas the growth of uninfected MOLT4 was stimulated. This selective apoptosis did not occur with other adenine nucleotides or with other bases. The purine ring and the amino residue of adenine were responsible for the apoptosis induction and selectivity, respectively. In addition, adenine slightly but consistently reduced viable cell numbers and the production of virus in a fraction of HIV-1 chronically infected human peripheral blood mononuclear cells (PBMCs/HIV) at day 7. On the other hand, blastogenic response of normal PBMCs to PHA, PWM and Candida albicans were potentiated in the presence of adenine. These results indicated that the effect of adenine may be attributable to activation-induced selective apoptosis toward virus-infected cells.
Hirasawa
K
K
Viral Immunology Group, Central Research Laboratory of Fujirebio Inc. , Hachioji, Tokyo, 192-0031, Japan. keisuke-hirasawa@m05.htmnet.ne.jp
Yoshida
O
O
Fujinami
T
T
Sohma
K
K
Watanabe
A
A
D000225:Adenine / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D005434:Flow Cytometry; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans
D019380:Anti-HIV Agents; D000225:Adenine