Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0019693 (
HIV
)
170,526
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
. 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
9-13
. Vpx associated with the HUSH complex and decreased steady-state level of these proteins in a DCAF1/CUL4A/B/proteasome-dependent manner
14,15
. Replication kinetics of
HIV
-1 and SIV
MAC
was accelerated to a similar extent by vpx or FAM208A knockdown. Finally, vpx increased steady-state levels of LINE-1 ORF1p, as previously described for FAM208A disruption
11
. 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.
...
PMID:Primate immunodeficiency virus proteins Vpx and Vpr counteract transcriptional repression of proviruses by the HUSH complex. 3047 87
