title: Protein kinase C-delta regulates HIV-1 replication at an early post-entry step in macrophages.
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.
  
  
  CONCLUSIONS
  This work highlights the importance of PKC-delta during early steps of the replicative cycle of HIV-1 in human macrophages.
authors.affiliation: Université Paul Sabatier, EA 3038, 118 Route de Narbonne, Toulouse 31062, France. contreras.xavier@gmail.com
authors.forename: Xavier
authors.initials: X
authors.lastname: Contreras
authors.forename: Olfa
authors.initials: O
authors.lastname: Mzoughi
authors.forename: Fabrice
authors.initials: F
authors.lastname: Gaston
authors.forename: Matija B
authors.initials: MB
authors.lastname: Peterlin
authors.forename: Elmostafa
authors.initials: E
authors.lastname: Bahraoui
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D008841:Actin Cytoskeleton / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology; D015704:CD4 Antigens / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D048348:Reverse Transcription; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D015704:CD4 Antigens; D018076:DNA, Complementary; D007527:Isoenzymes; D034741:RNA, Small Interfering; D019713:Receptors, CCR5; C085746:rottlerin; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta