TREX1 and viral infectious disease: While the link between RNASEH2B deficiency and increased R-loop formation is consistent with the ability of the RNase H2 complex to degrade the RNA strand of RNA/DNA heteroduplexes, the connection between R-loop homeostasis and TREX1 is less evident, as the cytosolic DNA exonuclease has mainly been implicated in degradation of ssDNA and dsDNA in the context of viral infections such as HIV (Yan et al., 2010) or upon RT of the ERE LINE-1 (Stetson et al., 2008b).