HIV-1 Vpr—a still “enigmatic multitasker”

Abstract

Like other HIV-1 auxiliary proteins, Vpr is conserved within all the human (HIV-1, HIV-2) and simian (SIV) immunodeficiency viruses. However, Vpr and homologous HIV-2, and SIV Vpx are the only viral auxiliary proteins specifically incorporated into virus particles through direct interaction with the Gag precursor, indicating that this presence in the core of the mature virions is mainly required for optimal establishment of the early steps of the virus life cycle in the newly infected cell. In spite of its small size, a plethora of effects and functions have been attributed to Vpr, including induction of cell cycle arrest and apoptosis, modulation of the fidelity of reverse transcription, nuclear import of viral DNA in macrophages and other non-dividing cells, and transcriptional modulation of viral and host cell genes. Even if some more recent studies identified a few cellular targets that HIV-1 Vpr may utilize in order to perform its different tasks, the real role and functions of Vpr during the course of natural infection are still enigmatic. In this review, we will summarize the main reported functions of HIV-1 Vpr and their significance in the context of the viral life cycle.

Sensing of HIV-1 Infection in Tzm-bl Cells with Reconstituted Expression of STING

“…Vpr, a 14-kDa multifunctional viral protein that is efficiently packaged into virus particles, has been implicated in the regulation of apoptosis of HIV-infected cells, the efficiency and accuracy of the reverse transcription process, and the nuclear import of viral genomes (60,61). Vpr has been most intensively studied for its ability to arrest the cell cycle of HIV target cells in G 2 (62)(63)(64)(65)(66)(67)(68).…”

“…As speculated by these authors, the effect of Vpr on cytokine induction may reflect a reduction of viral genomes available for sensing that results from triggered endonuclease activity of the SLX4 complex. Following virus entry, these genomes remain packaged together with Vpr within subviral cores that uncoat and deliver viral genomes to the nucleus via poorly defined mechanisms (60,75,76). An alternative and not mutually exclusive explanation for this shaping of innate immune recognition of HIV infection is that Vpr regulates the accessibility of viral genomes to cytoplasmic DNA sensors.…”

Glutamate metabolism in HIV-1 infected macrophages: Role of HIV-1 Vpr

“…10 Vpr is known to induce cell cycle arrest in G 2 /M phase. 11,12 Vpr-mediated pathogenesis in macrophages has been extensively investigated, [13][14][15] but its effects on the global molecular mechanism associated with metabolic pathways have not been characterized. Our recent SILAC-based proteomics study showed that HIV-1 Vpr overexpression in macrophages induces changes at the protein level in many of the enzymes involved in cellular metabolism.…”

Vpr Enhances Tumor Necrosis Factor Production by HIV-1-Infected T Cells

“…In HIV-infected humanized mice, T regulatory lymphocytes are arrested in the G 2 phase of the cell cycle upon infection and undergo apoptosis in a vpr-dependent fashion, leading to enhanced replication (65). Besides the SLX4com, Vpr interacts with numerous cellular proteins, but the relevance of these interactions is not always clear (66). For instance, Vpr degrades UNG2, a cellular protein involved in the removal of misincorporated uracil in DNA and for which a role during the HIV-1 life cycle remains a subject of debate (67)(68)(69).…”