NEAT1_1 and NEAT1_2 are related long noncoding RNAs (lncRNAs) that accumulate to high levels in the nucleus. NEAT1 RNAs serve as essential scaffolds to assemble nuclear structures termed paraspeckles that contain approximately 45 proteins in addition to the lncRNAs. Recent findings indicate that incompletely spliced HIV RNAs are retained in the nucleus through an association with paraspeckles. Importantly, NEAT1 RNAs are expressed at high levels in resting CD4 T cells, and their levels are strongly down-regulated by T cell activation. This expression pattern suggests that NEAT1 RNAs function to retain viral transcripts in the nucleus of quiescent CD4 T cells. The proposed research will investigate whether the nuclear retention of viral RNAs by NEAT1 RNAs acts to repress HIV replication in resting CD4 T cells, as well as to maintain HIV latency in resting CD4 T cells. Additionally, paraspeckle proteins include several RNA splicing factors and chromatin remodeling proteins. The research will therefore also examine if NEAT1 RNAs play roles in HIV RNA splicing and proviral transcription by RNA Polymerase II. Completion of the proposed research is likely to provide new insight into mechanisms of HIV gene regulation and viral latency.