HIV-1 Vpr: a multifunctional accessory protein with potential contributions to AIDS pathogenesis and persistence

Human immunodeficiency virus type 1 (HIV-1) infection can progress to acquired immune deficiency syndrome (AIDS), which is characterized by a rapid decline in CD4⁺ T lymphocyte counts, severe impairment of host immune competence, and recurrent opportunistic infections. Over the past four decades, HIV infection has remained one of the major threats to global public health. Viral protein R (Vpr) is one of nine proteins encoded by HIV RNA genome. Despite consisting of merely 96 amino acids, Vpr exerts multiple functions throughout viral infection and replication and is potentially associated with the progression of AIDS. In this review, we summarize the structural features and biological functions of Vpr, and focus on its multifaceted roles, including the induction of G2/M cell-cycle arrest and apoptotic cell death, facilitation of HIV-1 infection and replication via Env enhancement, modulation of cellular signaling cascades and host gene expression, and participation in AIDS progression. We also include Vpr-mediated regulation of human endogenous retroelement activity and its potential impacts on cellular innate immune responses. This work aims to provide novel analytical perspectives and research directions for in-depth elucidation of Vpr functions and their contributions to AIDS pathogenesis.