Author/Editor		Contreras, Xavier; Mzoughi, Olfa; Gaston, Fabrice; Peterlin, Matija Boris; Bahraoui, Elmostafa
Title		Protein kinase C-delta regulates HIV-1 replication at an early post-entry step in macrophages
Type		članek
Vol. and No.		Letnik 9, št. 37
Publication year		2012
ISSN		1742-4690 - Retrovirology
Language		eng
Abstract		Background Macrophages, which are CD4 and CCR5 positive, can sustain HIV-1 replication for long periods of time. Thus, these cells play critical roles in the transmission, dissemination and persistence of viral infection. Of note, current antiviral therapies do not target macrophages efficiently. Previously, it was demonstrated that interactions between CCR5 and gp120 stimulate PKC. However, the PKC isozymes involved were not identified. Results In this study, we identified PKC-delta as a major cellular cofactor for HIV-1 replication in macrophages. Indeed, PKC-delta was stimulated following the interaction between the virus and its target cell. Moreover, inhibition of PKC-delta blocked the replication of R5-tropic viruses in primary human macrophages. However, this inhibition did not have significant effects on receptor and co-receptor expression or fusion. Additionally, it did not affect the formation of the early reverse transcription product containing R/U5 sequences, but did inhibit the synthesis of subsequent cDNAs. Importantly, the inhibition of PKC-delta altered the redistribution of actin, a cellular cofactor whose requirement for the completion of reverse transcription was previously established. It also prevented the association of the reverse transcription complex with the cytoskeleton. Conclusion This work highlights the importance of PKC-delta during early steps of the replicative cycle of HIV-1 in human macrophages.
Keywords		protein-kinaze C-delta makrofagi HIV-1 protein kinase C-delta macrophages HIV-1