Upregulation of HIV-1 replication in chronically infected cells by ingenol derivatives.
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.
Fujiwara
M
M
Rational Drug Design Laboratories, Fukushima, Japan.
Okamoto
M
M
Ijichi
K
K
Tokuhisa
K
K
Hanasaki
Y
Y
Katsuura
K
K
Uemura
D
D
Shigeta
S
S
Konno
K
K
Yokota
T
T
Baba
M
M
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*
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