Human immunodeficiency virus (HIV-1) infection is followed by a period of latency or a low-levelpersistent (LLP) necrosis factor a that leads to the inhibition of intracellular viral protein synthesis and viral shedding. G( 6976 also blocks interleukin 6-mediated posttranscriptional induction of viral proteins. The ICso of G6 6976 shows a 12-to 60-fold more potent effect than for H-7, another PKC inhibitor with a similar mechanism. The inhibitory effect is reduced when Go 6976 is not added before or within 1 hr of induction by the potent PKC activator Bryostatin 1. However, Ul cells can be grown for long periods in a nontoxic concentration of Go 6976 (300 nW, which confers virtual inhibition of HIV-1 induction without the development of resistance. Results indicate that inhibition of HIV-1 proviral induction from latent/low-level-producing infectious states with potent PKC inhibitors like (1 6976 may represent an additional and promising antiviral approach.
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