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. 2012:2012:805347.
doi: 10.1155/2012/805347. Epub 2012 Mar 5.

Protein Kinase C: One Pathway towards the Eradication of Latent HIV-1 Reservoirs

Lisa N McKernan  1 , David Momjian, Joseph Kulkosky
Affiliations

Protein Kinase C: One Pathway towards the Eradication of Latent HIV-1 Reservoirs

Lisa N McKernan et al. Adv Virol. 2012.

Abstract

An effective means to eradicate latent reservoirs in HIV-1-infected individuals remains elusive. Attempts to purge these reservoirs were undertaken over a decade ago without success. The subsequent lapse in further clinical attempts since may have been justified as our knowledge of the mechanisms which underpin the latent state still evolves. Although additional novel molecular antagonists of HIV-1 latency have subsequently been reported, these candidate agents have not been tested in human trials for reservoir ablation. This review provides an overview of the protein kinase C (PKC) pathway which can be modulated by small molecular agents to induce the expression of latent HIV-1 from within infected reservoir cells. Some of these agents have been tested against select cancers with seemingly tolerable side effects. As such, modulation of the PKC pathway may yet be a viable mechanism toward HIV-1 reservoir eradication.

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Figures

Figure 1
Figure 1
Overview of the mechanistic steps involved in PKC modulation toward the upregulation of latent HIV-1. PKC modulating agents represent functional analogues of DAG that similarly activate the PKC cascade.
Figure 2
Figure 2
Critical transcription factor binding sites within the HIV-1 long terminal repeat (LTR) that facilitate upregulation of latent HIV-1.
Figure 3
Figure 3
Morphological and apoptotic effects of PMA and prostratin on select cell lines. Top panel: 293 adherent cells. Lower panel: Jurkat cells. Concentrations of prostratin at or below 10 μM, higher than required to upregulate latent HIV-1, do not markedly alter morphogenesis or induce apoptosis. Concentrations >10 μM affect both cellular processes.
Figure 4
Figure 4
Comparative chemical structures of PKC-modulating agents.
See this image and copyright information in PMC

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