Primate immunodeficiency virus proteins Vpx and Vpr counteract transcriptional repression of proviruses by the HUSH complex.

ABSTRACT: Host factors that silence provirus transcription in CD4⁺ memory T cells help HIV-1 escape eradication by the host immune system and by antiviral drugs¹. These same factors, however, must be overcome for HIV-1 to propagate. Here we show that Vpx and Vpr encoded by diverse primate immunodeficiency viruses activate provirus transcription. Vpx and Vpr are adaptor proteins for the DCAF1-CUL4A/B E3 ubiquitin ligase that degrade SAMHD1 and increase reverse transcription^2-4. Nonetheless, Vpx and Vpr have effects on reporter gene expression that are not explained by SAMHD1 degradation^5-8. A screen for factors that mimic these effects identified the human silencing hub (HUSH) complex, FAM208A (TASOR/RAP140), MPHOSPH8 (MPP8), PPHLN1 (PERIPHILIN) and MORC2

SUBMITTER: Yurkovetskiy L 

PROVIDER: S-EPMC6258279 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature