Retroviruses such as human immunodeficiency virus (HIV) can infect dendritic cells, but cellular innate immune responses limit their productive replicative capacity. In Cell, Yoh et al. identify the polyglutamine-binding protein PQBP1 as a cytosolic sensor of retroviral cDNA intermediates. HIV infection of primary human dendritic cells is detected by PQBP1, which can interact directly with an early intermediate form of HIV cDNA. PQBP1 acts upstream of the DNA sensor cGAS to activate the transcription factor IRF3. This recognition of viral cDNA triggers dendritic cell expression of type I interferons and upregulation of interferon-response genes. How PQBP1 distinguishes HIV cDNA from other forms of cytosolic nucleic acids remains unknown.

Cell 161, 1293–1305 (2015)