![]() ![]() Vpx rescues HIV-1 transduction of dendritic cells from the antiviral state established by type 1 interferon. The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx. ![]() ![]() SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4 + T cells. These results demonstrate that the HUSH complex represses primate immunodeficiency virus transcription, and that, to counteract this restriction, viral Vpx or Vpr proteins degrade the HUSH complex. Finally, vpx increased steady-state levels of LINE-1 ORF1p, as previously described for FAM208A disruption 11. Replication kinetics of HIV-1 and SIV MAC was accelerated to a similar extent by vpx or FAM208A knockdown. Vpx associated with the HUSH complex and decreased steady-state level of these proteins in a DCAF1/CUL4A/B/proteasome-dependent manner 14, 15. A screen for factors that mimic these effects identified the human silencing hub (HUSH) complex, FAM208A (TASOR/RAP140), MPHOSPH8 (MPP8), PPHLN1 (PERIPHILIN) and MORC2 9, 10, 11, 12, 13. Nonetheless, Vpx and Vpr have effects on reporter gene expression that are not explained by SAMHD1 degradation 5, 6, 7, 8. ![]() Vpx and Vpr are adaptor proteins for the DCAF1-CUL4A/B E3 ubiquitin ligase that degrade SAMHD1 and increase reverse transcription 2, 3, 4. Here we show that Vpx and Vpr encoded by diverse primate immunodeficiency viruses activate provirus transcription. These same factors, however, must be overcome for HIV-1 to propagate. Host factors that silence provirus transcription in CD4 + memory T cells help HIV-1 escape eradication by the host immune system and by antiviral drugs 1. ![]()
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