title: All-trans retinoic acid attacks reverse transcriptase resulting in inhibition of HIV-1 replication.
abstract: 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.
authors.affiliation: Department of Hematology, Kinki University School of Medicine, Osaka, Japan. ymaeda@med.kindai.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Terufumi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Hijikata
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Morita
authors.forename: Miyako
authors.initials: M
authors.lastname: Tanaka
authors.forename: Chikara
authors.initials: C
authors.lastname: Hirase
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Takai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tatsumi
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kanamaru
mesh_terms: 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
chemical_list: D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D014212:Tretinoin; D012194:RNA-Directed DNA Polymerase