Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Retrovirology cung cấp cho các bạn kiến thức về ngành y đề tài: GCN5-dependent acetylation of HIV-1 integrase enhances viral integration. | Terreni et al. Retrovirology 2010 7 18 http content 7 1 18 RETR0VIR0L0GY RESEARCH Open Access GCN5-dependent acetylation of HIV-1 integrase enhances viral integration 1 1 1 2 1 3 Mariaelena Terreni Paola Valentini Vania Liverani Maria Ines Gutierrez Cristina Di Primio Armida Di Fenza Valentina Tozzini3 Awatef Allouch1 Alberto Albanese3 Mauro Giacca2 Anna Cereseto1 Abstract Background An essential event during the replication cycle of HIV-1 is the integration of the reverse transcribed viral DNA into the host cellular genome. Our former report revealed that HIV-1 integrase IN the enzyme that catalyzes the integration reaction is positively regulated by acetylation mediated by the histone acetyltransferase HAT p300. Results In this study we demonstrate that another cellular HAT GCN5 acetylates IN leading to enhanced 3 -end processing and strand transfer activities. GCN5 participates in the integration step of HIV-1 replication cycle as demonstrated by the reduced infectivity due to inefficient provirus formation in GCN5 knockdown cells. Within the C-terminal domain of IN four lysines K258 K264 K266 and K273 are targeted by GCN5 acetylation three of which K264 K266 and K273 are also modified by p300. Replication analysis of HIV-1 clones carrying substitutions at the IN lysines acetylated by both GCN5 and p300 or exclusively by GCN5 demonstrated that these residues are required for efficient viral integration. In addition a comparative analysis of the replication efficiencies of the IN triple- and quadruple-mutant viruses revealed that even though the lysines targeted by both GCN5 and p300 are required for efficient virus integration the residue exclusively modified by GCN5 K258 does not affect this process. Conclusions The results presented here further demonstrate the relevance of IN post-translational modification by acetylation which results from the catalytic activities of multiple HATs during the viral replication cycle. Finally this study .
