In contrast to IKAROS defects but similar to cytotoxic T lymphocyte–associated protein 4 (CTLA4) haploinsufficiency, we observed that NFKB1 haploinsufficiency can also result in chronic and severe viral disease, as noted for cytomegalovirus and JC virus infections in 3 of our patients. Here, NFKB1 is linked to viral load.