Vpr

Source: Wikipedia, the free encyclopedia.
VPR
TCDB
1.A.42
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Vpr is a

HIV-1 pre-integration complex, and is required for virus replication and enhanced gene expression from provirus in dividing or non-dividing cells such as T cells or macrophages.[3] Vpr also induces G2 cell cycle arrest and apoptosis in proliferating cells, which can result in immune dysfunction.[4][5]

Vpr is also

HIV-2
, with the HIV-2 Vpr protein inducing cell cycle arrest and the Vpx protein required for nuclear import.

Vpr-binding protein

Vpr-binding protein (VprBP) is a 1,507-amino-acid human protein that contains conserved domains, including YXXY repeats, the

E3 ubiquitin ligase complex.[6] When bound to Vpr, VprBP allows Vpr to modulate the catalytic activity of the CUL4–DDB1 complex, inducing G2 cell cycle arrest in infected cells.[6]

VprBP also regulates p53-induced transcription and apoptotic pathways. p53 is an important tumor suppressor which induces either cell cycle arrest or apoptosis in response to DNA damage.[6]

In-vitro studies of Vpr

The lack of an in vitro cell culture system that demonstrated a deficit in replication upon infection with viruses in the absence of Vpr has led to some mystery in the function of Vpr. Recently, there has been experiments on monocyte-derived dendritic cells (MDDCs) using a novel in-vitro infection system. These infected human dendritic cells showed a slower rate of replication when deprived of the Vpr protein in HIV-1 cells. This replication difference occurred in a single round of infection. This was shown to be due to decreased transcriptional output from the integrated HIV viral genome. Using mutational analysis (biochemical identification of mutational changes in a nucleotide sequence), prevention of cell cycle progression into mitosis was shown to be required for LTR-mediated viral expression. These findings suggest that the evolutionarily secured G2 cell cycle arrest function of Vpr (Viral Protein R) is essential for HIV-1 replication. Furthermore, this innovative in-vitro culture system will allow researchers to address mechanisms underlying Vpr-mediated enhancement of HIV-1 replication.[7]

References

This page is based on the copyrighted Wikipedia article: Vpr. Articles is available under the CC BY-SA 3.0 license; additional terms may apply.Privacy Policy