Eukaryotic chromatin harbors a variety of structures and its dynamics is key in many cellular processes like DNA replication, transcription and repair. High order folding of the chromatin is mediated by histone H4 N-terminal tail interaction with the acidic patch of the neighboring nucleosome. Interestingly the acidic patch acts as a docking station for several viral proteins like Kaposi sarcoma herpes virus LANA, cytomegalovirus IE1 or spumaretrovirus Gag. It has been shown that LANA and IE1 can affect in vitro high order structure of chromatin but the functional significance of this phenomenon remains unclear. Recently we solved the structure of retroviral Gag protein bound to the nucleosome acidic patch and showed that this interaction is crucial for optimum viral infectivity. Here we aim at deciphering the molecular mechanism of the viral proteins tethering to nucleosome and the consequences on both the viral replication and host chromatin architecture in cellulo.