Maeda Yasuhiro, Yamaguchi Terufumi, Hijikata Yasuki, Morita Yasuyoshi, Tanaka Miyako, Hirase Chikara, Takai Shunsuke, Tatsumi Yoichi, Kanamaru Akihisa
Department of Hematology, Kinki University School of Medicine, Osaka, Japan.
Hematology. 2007 Jun;12(3):263-6. doi: 10.1080/10245330701255130.
We previously reported that all-trans retinoic acid (ATRA) inhibited growth in HTLV-1-positive T-cell lines and fresh cells from patients with adult T-cell leukemia. Interestingly, ATRA significantly inhibited reverse transcriptase (RT) activity similar to azidothimidine (AZT) in HTLV-1-positive T-cell lines. To clarify whether ATRA has an inhibitory effect on the replication of HIV, we examined HIV proviral DNA in a HIV-1-positive cell line (8E5) using real time PCR. ATRA as well as AZT reduced the proviral DNA load of 8E5 in a dose-dependent manner. These results suggest that there is a common element of ATRA signaling in both HTLV-1 and HIV. Furthermore, we examined the effects of ATRA on viral replication in primary lymphocytes of three individuals infected with HIV. ATRA reduced viral replication significantly similar to AZT. These findings suggested that ATRA acts as a RT inhibitor, reducing the HIV-1 proviral DNA load. Finally, we conclude that ATRA may be a potential therapeutic agent for HIV infection.
我们之前报道过，全反式维甲酸（ATRA）可抑制HTLV-1阳性T细胞系以及成人T细胞白血病患者新鲜细胞的生长。有趣的是，在HTLV-1阳性T细胞系中，ATRA显著抑制逆转录酶（RT）活性，其作用类似于叠氮胸苷（AZT）。为了阐明ATRA是否对HIV复制有抑制作用，我们使用实时PCR检测了HIV-1阳性细胞系（8E5）中的HIV前病毒DNA。ATRA和AZT均以剂量依赖的方式降低了8E5的前病毒DNA载量。这些结果表明，在HTLV-1和HIV中存在ATRA信号传导的共同元件。此外，我们检测了ATRA对三名HIV感染者原代淋巴细胞中病毒复制的影响。ATRA与AZT类似，显著降低了病毒复制。这些发现表明，ATRA作为一种RT抑制剂，可降低HIV-1前病毒DNA载量。最后，我们得出结论，ATRA可能是一种潜在的HIV感染治疗药物。
