Upregulation of HIV-1 replication in chronically infected cells by ingenol derivatives

• DOI: 10.1007/s007050050436
• Publication Date: 2002-08-25T05:09:23Z
• Authors: M. Fujiwara; M. Okamoto; K. Ijichi; K. Tokuhisa; Y. Hanasaki; K. Katsuura; D. Uemura; S. Shigeta; K. Konno; T. Yokota; M. Baba
• Keywords: 0301 basic medicine; HIV Core Protein p24; NF-kappa B; Virus Replication; Up-Regulation; 3. Good health; Butyrates; 03 medical and health sciences; Calcium-Calmodulin-Dependent Protein Kinases; HIV-1; Humans; Diterpenes; Protein Kinase C

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.