Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UMLS:C0019693 (
HIV
)
170,526
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Host cell factors can either positively or negatively regulate the assembly and egress of
HIV
-1 particles from infected cells. Recent reports have identified a previously uncharacterized transmembrane protein, tetherin/CD317/BST-2, as a crucial host restriction factor that acts during a late budding step in
HIV
-1 replication by inhibiting viral particle release. Although tetherin has been shown to promote the retention of nascent viral particles on the host cell surface, the precise molecular mechanisms that occur during and after these tethering events remain largely unknown. We here report that a RING-type E3 ubiquitin ligase, BCA2 (Breast cancer-associated gene 2; also called Rabring7,
ZNF364
or RNF115), is a novel tetherin-interacting host protein that facilitates the restriction of
HIV
-1 particle production in tetherin-positive cells. The expression of human BCA2 in "tetherin-positive" HeLa, but not in "tetherin-negative" HOS cells, resulted in a strong restriction of
HIV
-1 particle production. Upon the expression of tetherin in HOS cells, BCA2 was capable of inhibiting viral particle production as in HeLa cells. The targeted depletion of endogenous BCA2 by RNA interference (RNAi) in HeLa cells reduced the intracellular accumulation of viral particles, which were nevertheless retained on the plasma membrane. BCA2 was also found to facilitate the internalization of
HIV
-1 virions into CD63(+) intracellular vesicles leading to their lysosomal degradation. These results indicate that BCA2 accelerates the internalization and degradation of viral particles following their tethering to the cell surface and is a co-factor or enhancer for the tetherin-dependent restriction of
HIV
-1 release from infected cells.
...
PMID:BCA2/Rabring7 promotes tetherin-dependent HIV-1 restriction. 2001 14
BCA2 (Rabring7, RNF115 or
ZNF364
) is a RING-finger E3 ubiquitin ligase that was identified as a co-factor in the restriction imposed by tetherin/BST2 on
HIV
-1. Contrary to the current model, in which BCA2 lacks antiviral activity in the absence of tetherin, we found that BCA2 possesses tetherin-independent antiviral activity. Here we show that the N-terminus of BCA2 physically interacts with the Matrix region of
HIV
-1 and other retroviral Gag proteins and promotes their ubiquitination, redistribution to endo-lysosomal compartments and, ultimately, lysosomal degradation. The targeted depletion of BCA2 in tetherin-expressing and tetherin-deficient cells results in a significant increase in virus release and replication, indicating that endogenous BCA2 possesses antiviral activity. Therefore, these results indicate that BCA2 functions as an antiviral factor that targets
HIV
-1 Gag for degradation, impairing virus assembly and release.
...
PMID:BCA2/Rabring7 targets HIV-1 Gag for lysosomal degradation in a tetherin-independent manner. 2485 21
