Model for Vpr-mediated evasion from immune sensing. The model envisioned by Laguette et al. proposes that HIV DNA forms accumulate following infection by a Vpr-deleted HIV-1 virus (HIV-1∆Vpr). These forms, that are not characterized, are sensed by a DNA immune sensor to generate an IFN response (left panel). A Vpr encoding HIV-1 virus would instead force the SLX4com endonuclease activity. The subsequent processing of extra reverse transcription products would help to prevent their accumulation and allow escape from immune sensing (right panel). How does SLX4com distinguish between the unproductive and the productively infecting RT intermediates is unknown. In addition, whether Vpr increases the efficiency of viral infection by activating SLX4 has not been investigated yet.