Protein Vpr (R ORF protein) (Viral protein R) (Fragment)

NC_001802.1 ;  AF033819.3 

NSATTAVYSFQDWVSA

Involved in the transport of the viral pre-integration (PIC) complex to the nucleus during the early stages of the infection. This function is crucial for viral infection of non-dividing macrophages. May interact with karyopherin alpha/KPNA1 and KPNA2 to increase their affinity for proteins containing basic-type nuclear localization signal, including the viral matrix protein MA, thus facilitating the translocation of the viral genome into the nucleus. May also act directly at the nuclear pore complex, by binding nucleoporins phenylalanine-glycine (FG)-repeat regions. Has an anti-apoptotic effect, whereas high level of expression induces apoptosis. Interacts with mitochondrial permeability transition pore complex (PTPC), presumably through the binding of ANT proteins. This induces a rapid dissipation of the mitochondrial transmembrane potential, and mitochondrial release of apoptogenic proteins such as cytochrome C or apoptosis inducing factors. Prevents infected cells from undergoing mitosis and proliferating, by inducing arrest or delay in the G2 phase of the cell cycle. The arrest in G2 is characterized by low levels of CCNB1-CDC2 complex and corresponding inhibitory phosphorylation of CDC2. Cell cycle arrest creates a favorable environment for maximizing viral expression and production. This may be mediated by interacting with and inhibiting human CDC25C, which normally activates the CCNB1-CDC2 complex, or by binding SF3B2/SAP145. This function is independent of nuclear localization. Cell cycle arrest reportedly occurs within hours of infection and is not blocked by antiviral agents, suggesting that it is initiated by the Vpr carried into the virion. Stimulates gene expression driven by the HIV-1 LTR by interacting with human SP1, TFIIB and TFIID. Moreover, the G2/M cell cycle arrest creates a cellular environment where the HIV-1 LTR is transcriptionally more active. Essential for unintegrated viral DNA expression. Detected in the serum and cerebrospinal fluid of AIDS patient, where it may induce cell death to bystander cells. This necrotic or apoptotic effect might function by entering target cell plasma membrane to form ion channel (By similarity).

Virion. Host nucleus. Host extracellular space. Note=Incorporation into virion is dependent on p6 GAG sequences. Lacks a canonical nuclear localization signal, thus import into nucleus may function independently of the human importin pathway. Detected in high quantity in the serum and cerebrospinal fluid of AIDS patient (By similarity). .

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