doi:10.5402/2011/248280 Research Article InVivo Effects of Antiviral Protein Kinase C Modulators on Zebrafish Development and Survival

Copyright © 2011 Richard V. Davis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Clinical interventions using protein kinase C (PKC) modulators have been proposed for eradication of HIV-1-infected cellular reservoirs which persist in patients despite prolonged antiretroviral therapy. The effects of some of these agents have not been assessed in a developing vertebrate model. This study examines the developmental and toxicological effects of these compounds on zebrafish embryos and larvae. Treatment of zebrafish through the first week of development with various PKC pathwaymodulators did not elicit gross physical defects or elevated incidences of death at lower doses. Higher concentrations resulted in rapid death for both later-stage embryos and larvae. Each compound had a threshold dose for lethality. The defined nonlethal doses may be useful toward assessing the effects of modulating PKC activity on zebrafish development. They may further provide some guidance for the potential dosing of PKC modulators in clinical trials toward the goal of HIV-1 reservoir eradication. 1