HIV-1 Vpr and its Vpr/Vpx homologs in HIV-2 and SIV associate with the cullin4A-DDB1-DCAF1 complex to target multiple host factors including tet methylcytosine dioxygenase 2 (TET2) and helicase-like transcription factor (HLTF) for degradation, thus promoting virus infection [103,104]. Here, TET2 is linked to viral infectious disease.