Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1.

Abstract

In human immunodeficiency virus (HIV)-positive individuals, the vast majority of infected peripheral blood cells and lymph node cells may be latently or nonproductively infected. The vpr open reading frame of HIV-1 encodes a 15-kDa virion-associated protein, Vpr. The vpr gene has been shown to increase virus replication in T cells and monocyte/macrophages in vitro. We have previously reported that vpr expression in various tumor lines leads to growth inhibition and differentiation, indicating that Vpr may function as a regulator of cellular permissiveness to HIV replication. Here we show that Vpr protein is present in significant amounts in the serum of AIDS patients. Purified serum Vpr activated virus expression from five latently infected cell lines, U1, OM.10.1, ACH-2, J1.1, and LL58. Serum Vpr also activated virus expression from resting peripheral blood mononuclear cells of HIV-infected individuals. Together, these findings implicate serum Vpr in the activation of HIV replication in vivo and in the control of latency. Anti-Vpr antibodies inhibited Vpr activity, suggesting that humoral immunity modulates Vpr activity in vivo. These results have broad implications for the virus life cycle and for the prospective control of HIV replication and pathogenesis.

Functional and Structural Characterization of Synthetic HIV-1 Vpr That Transduces Cells, Localizes to the Nucleus, and Induces G2 Cell Cycle Arrest

“…2C). Together, these findings demonstrate the usefulness of R96 for detection of viral Vpr in serum samples of HIV-infected individuals (23).…”

“…Recombinant Vpr has been produced in insect cells and as a glutathione S-transferase fusion protein in Escherichia coli (15). At concentrations as low as 100 pg/ml, the extracellular addition of recombinant Vpr activates HIV-1 replication in both leukemic cell lines and primary peripheral blood mononuclear cells (23,24). However, when maintained at high concentrations as required for structural investigation, preparations of recombinant Vpr often undergo spontaneous aggregation.…”

HIV-1 Vpr induces ATM-dependent cellular signal with enhanced homologous recombination

“…Recently, we also found that Vpr is present in serum of HIV-1-positive patients (Levy et al, 1994) at the concentration of about 0.7 nM (Hoshino et al, submitted). In the current study, we used 3.7 nM of rVpr to obtain the definite activity inducing DSBs, but it would be possible that the high concentration of Vpr is present in the foci of HIV-1 infection, suggesting that DSBs can be generated in the cells within HIV-1-positive patients.…”

Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism

“…For instance, a functional Vpr protein has been purified from serum and cerebrospinal fluid of infected patients. 8 The purified Vpr has been shown to have transactivational and cytotoxic properties in CD4 þ T cells and neurons, respectively. [8][9][10] Such results suggest that Vpr's cellular effects can manifest through various mechanisms including entry of free Vpr into uninfected, activated CD4 þ T cells for destruction.…”