title: Upregulation of HIV-1 replication in chronically infected cells by ingenol derivatives.
abstract: We have previously reported that ingenol derivatives are highly potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in acutely infected cells. In this study, however, we have found that some ingenol derivatives strongly enhance the replication of HIV-1 in chronically infected cells at nanomolar concentrations. One of the derivatives could activate nuclear factor kappa B (NF-kappa B), a potent inducer of HIV-1 replication, through the activation of protein kinase C (PKC). Whereas another derivative, which affected neither PKC nor NF-kappa B, significantly enhanced HIV-1 replication, suggesting that a PKC-independent mechanism may also exist in ingenol derivative-induced HIV-1 upregulation.
authors.affiliation: Rational Drug Design Laboratories, Fukushima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fujiwara
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: K
authors.initials: K
authors.lastname: Ijichi
authors.forename: K
authors.initials: K
authors.lastname: Tokuhisa
authors.forename: Y
authors.initials: Y
authors.lastname: Hanasaki
authors.forename: K
authors.initials: K
authors.lastname: Katsuura
authors.forename: D
authors.initials: D
authors.lastname: Uemura
authors.forename: S
authors.initials: S
authors.lastname: Shigeta
authors.forename: K
authors.initials: K
authors.lastname: Konno
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: M
authors.initials: M
authors.lastname: Baba
mesh_terms: D002087:Butyrates / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D002087:Butyrates; D004224:Diterpenes; D016655:HIV Core Protein p24; D016328:NF-kappa B; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C008125:ingenol