All-trans retinoic acid attacks reverse transcriptase resulting in inhibition of HIV-1 replication.
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.
Maeda
Yasuhiro
Y
Department of Hematology, Kinki University School of Medicine, Osaka, Japan. ymaeda@med.kindai.ac.jp
Yamaguchi
Terufumi
T
Hijikata
Yasuki
Y
Morita
Yasuyoshi
Y
Tanaka
Miyako
M
Hirase
Chikara
C
Takai
Shunsuke
S
Tatsumi
Yoichi
Y
Kanamaru
Akihisa
A
D002460:Cell Line; D002478:Cells, Cultured; D004279:DNA, Viral / Q000097:blood; D015658:HIV Infections; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology
D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D014212:Tretinoin; D012194:RNA-Directed DNA Polymerase