The majority of the human transcriptome consists of long non-coding RNAs (lncRNAs), which regulate the expression and function of protein coding genes, immune cell development, differentiation, and response to infections. The role of lncRNAs in HIV-infected cells and how the host lncRNAs impact the replication and persistence of HIV infection is not known. The objective of this proposal is to identify host lncRNAs that influence viral replication, cellular and immune responses to infection and molecular mechanisms of their action.