Liquid-liquid phase separation of LARP7 restrains HIV-1 replication.

HIV-1 initiates replication by its transactivator Tat, hijacking the positive transcription elongation factor b (P-TEFb) in the host cell. Most P-TEFb is maintained in an inactive state by 7SK snRNP until it is brought to the transcription initiation complex by cellular or viral transactivators that accelerate transcription and facilitate the production of full-length viral transcripts. Here, we report that HIV-1 infection triggers liquid-liquid phase separation of LARP7, a central component of 7SK snRNP. Tat is incorporated into HIV-1-induced LARP7 condensates after infection. Conserved lysine residues in the intrinsically disordered region of LARP7 are essential for both its phase separation and the inhibition of Tat-mediated transcription. These findings identify a mechanism wherein P-TEFb and Tat are sequestered within LARP7 condensates, restraining HIV-1 transcription.