A major challenge to the current efforts to cure HIV-1 infection is the persistence of latent viruses. Addressing this challenge hinges on unraveling the intricate interplay between the host and viral factors that are key for HIV-1 latency. Current antiretroviral agents effectively prevent actively transcribing viruses from replicating but have no activity against the latent viral reservoirs. One of the underlying obstacles is to identify the key chromatin-associated host protein(s) that interacts with the 5’ long terminal repeats (LTR) containing the viral gene promoter and controls viral transcription during latency reactivation. Such interactions are pivotal in determining the fate of a virus -- latency versus reactivation -- a balance that must be understood in order for us to achieve the elusive goal of a functional cure for HIV. Protein arginine methyltransferase 3 (PRMT3), a member of the protein arginine methyltransferase family, functions in epigenetic regulation of gene expression through histone modification and is implicated in a wide array of normal and diseases processes ranging from carcinogenesis, hepatic steatosis, to antiviral innate immunity . Given its diverse physiological and pathological functions, significant attention has been directed toward the exploration and development of selective allosteric inhibitors of PRMT3. Despite its well-established functions in many processes of a host cell, the role of PRMT3 in regulating HIV-1 transcriptional reactivation and latency reversal remains largely unclear. Here, we applied a nuclease-deactivated Cas9 (dCas9)-based DNA-protein interaction screen to investigate host proteins that potentially interact with the HIV-1 5’ LTR.