HIV-1 Vpr Induces Widespread Transcriptomic Changes in CD4 + T Cells Early Postinfection

The interactions between a virus and its host are complex but can be broadly categorized as either viral manipulation of cellular functions or cellular responses to infection. These processes begin at the earliest point of contact between virus and cell and frequently result in changes to cellular gene expression, making genome-wide transcriptomics a useful tool to study them. Several previous studies have used transcriptomics to evaluate the cellular responses to human immunodeficiency virus type 1 (HIV-1) infection; however, none have examined events in primary CD4 + T cells during the first 24 h of infection. Here, we analyzed CD4 + T cells at 4.5, 8, 12, 24, and 48 h following infection. We describe global changes to host gene expression commencing at 4.5 h postinfection and evolving over the ensuing time points. We identify upregulation of genes related to innate immunity, cytokine production, and apoptosis and downregulation of those involved in transcription and translation. We further demonstrate that the viral accessory protein Vpr is necessary for almost all gene expression changes seen at 12 h postinfection and the majority of those seen at 48 h. Identifying this new role for Vpr not only provides fresh perspective on its possible function but also adds further insight into the interplay between HIV-1 and its host at the cellular level.