Protein kinase Ctheta is a specific target for inhibition of the HIV type 1 replication in CD4+ T lymphocytes

Integration of HIV-1 genome in CD4(+) T cells produces latent reservoirs with long half-life that impedes the eradication of the infection. Control of viral replication is essential to reduce the size of latent reservoirs, mainly during primary infection when HIV-1 infects CD4(+) T cells massively. The addition of immunosuppressive agents to highly active antiretroviral therapy during primary infection would suppress HIV-1 replication by limiting T cell activation, but these agents show potential risk for causing lymphoproliferative disorders. Selective inhibition of PKC, crucial for T cell function, would limit T cell activation and HIV-1 replication without causing general immunosuppression due to PKC being mostly expressed in T cells. Accordingly, the effect of rottlerin, a dose-dependent PKC inhibitor, on HIV-1 replication was analyzed in T cells. Rottlerin was able to reduce HIV-1 replication more than 20-fold in MT-2 (IC(50) = 5.2 μM) and Jurkat (IC(50) = 2.2 μM) cells and more than 4-fold in peripheral blood lymphocytes (IC(50) = 4.4 μM). Selective inhibition of PKC, but not PKCδ or -ζ, was observed at