HIV-2

HIV-2 is a lentiviral human immunodeficiency virus that causes AIDS but usually shows lower plasma viral load, slower CD4⁺ T-cell decline, and reduced transmission compared with HIV-1^[1][2]. Mechanistically, HIV-2 encodes Vpx, which induces proteasomal degradation of SAMHD1, relieves reverse-transcription restriction in myeloid cells and resting CD4⁺ T cells, and increases viral DNA synthesis in restrictive cellular models^[3][4][5]. HIV-2/SIV Vpx also counteracts the HUSH repressor complex, linking intrinsic immunity with epigenetic control of proviral expression in primary CD4⁺ T cells^[6]. In disease models and longitudinal cohorts, plasma viral load predicts CD4⁺ T-cell decline in HIV-2, and untreated HIV-2 can still progress to AIDS and death despite delayed disease kinetics^[2][7]. Compared with related isoforms, HIV-2 encodes both Vpx and Vpr, whereas HIV-1 encodes Vpr but not Vpx, making Vpx a key experimental marker distinguishing HIV-2 biology^[8]. For research applications, HIV-2 drug studies must account for intrinsic resistance to NNRTIs and enfuvirtide and for distinct resistance pathways under antiretroviral pressure^[9].