Role of Protein Kinase C Isozymes in Activation of Human Immunodeficiency Virus Type 1 in Chronically Infected Promonocytic Cells: Evidence Against a Role of PKCβ1

Abstract

Protein kinase C (PKC) plays an important role in activation of human immunodeficiency virus type 1 (HIV-1). Because of a molecular and biochemical heterogeneity of PKC, we have studied the effects of PKC isozymes in HIV-1 activation in a latently infected promonocytic cell line, U1, using various PKC isozyme agonists. 12-Deoxyphrbol 13-phenylacetate (dPP), an agonist of both Ca ++-dependent and Ca ++-independent isozymes, and thymeleatoxin (TT), an agonist of Ca ++-dependent PKC isozymes, induced HIV-1 production at 10 nM with increase in a concentration dependent manner, whereas 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), an PKCβI isozyme agonist, did not induce viral production at 100 nM. We verified that dPPA induced translocation of PKCβ isozyme with the isozyme-specific monoclonal antibody using flow cytometry. This study demonstrates that activation of PKC isozymes leads to an induction of latent HIV-1 in U1 cells whereas PKCβI isozyme may not be important.