HUSH, a Link Between Intrinsic Immunity and HIV Latency.

A prominent obstacle to HIV eradication in seropositive individuals is the viral persistence in latent reservoir cells, which constitute an HIV sanctuary out of reach of highly active antiretroviral therapies. Thus, the study of molecular mechanisms governing latency is a very active field that aims at providing solutions to face the reservoirs issue. Since the past 15 years, another major field in HIV biology focused on the discovery and study of restriction factors that shape intrinsic immunity, while engaging in a molecular battle against HIV.

HIV-2/SIV viral protein X counteracts HUSH repressor complex.

To evade host immune defences, human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) have evolved auxiliary proteins that target cell restriction factors. Viral protein X (Vpx) from the HIV-2/SIVsmm lineage enhances viral infection by antagonizing SAMHD1 (refs ), but this antagonism is not sufficient to explain all Vpx phenotypes. Here, through a proteomic screen, we identified another Vpx target-HUSH (TASOR, MPP8 and periphilin)-a complex involved in position-effect variegation.

HIV-1 Vpr degrades the HLTF DNA translocase in T cells and macrophages.

Viruses often interfere with the DNA damage response to better replicate in their hosts. The human immunodeficiency virus 1 (HIV-1) viral protein R (Vpr) protein has been reported to modulate the activity of the DNA repair structure-specific endonuclease subunit (SLX4) complex and to promote cell cycle arrest. Vpr also interferes with the base-excision repair pathway by antagonizing the uracil DNA glycosylase (Ung2) enzyme.