Abstract
The human immunodeficiency virus type 1 (HIV-1) accessory protein viral protein R (Vpr) is a major determinant for virus-induced G2/M cell cycle arrest and cytopathicity. Vpr is thought to perform these functions through the interaction with partner proteins. The NMR structure of Vpr revealed solvent exposed hydrophobic amino acids along helices 1 and 3 of Vpr, which could be putative protein binding domains. We previously showed that the hydrophobic patch along helix-3 was important for G2/M blockade and cytopathicity. Mutations of the exposed hydrophobic residues along helix-1 were found to reduce Vpr-induced cell cycle arrest and cell death as well. The levels of toxicity during virion delivery of Vpr correlated with G2/M arrest. Thus, the exposed hydrophobic amino acids in the amino-terminal helix-1 are important for the cell cycle arrest and cytopathicity functions of Vpr.
Highlights
The human immunodeficiency virus type 1 (HIV-1) accessory protein viral protein R (Vpr) has many well-characterized functions and properties during HIV-1 infection that appear to be dependent on binding to partner molecules [1,2]
Vpr likely functions by binding with partner proteins [1,2,28], and our lab has previously shown a role for the exposed hydrophobic patch along Vpr helix-3, an expected protein-protein interaction site, in the G2/M cell cycle arrest and cell death functions [18]
We present an analysis of another expected protein binding domain, the hydrophobic patch of Vpr helix-1, for Vpr-induced G2/M arrest and cytopathicity, as well as virion incorporation
Summary
The HIV-1 accessory protein Vpr has many well-characterized functions and properties during HIV-1 infection that appear to be dependent on binding to partner molecules [1,2]. Vpr is incorporated into budding HIV-1 virions [3], and within cells, Vpr mostly localizes to the nucleus [4]. These two properties are thought to allow Vpr to facilitate infection of non-dividing cells, by mediating the nuclear translocation of the viral pre-integration complex [5,6]. This is accomplished through an interaction with a member of the nuclear transport pathway, importin-a [7]. Vpr is able to halt the proliferation of infected CD4+ T cells by causing cell cycle arrest at the G2/M phase [22,23,24,25]
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