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 im-munodeficiency 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 tran-scription 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 pro-vides fresh perspective on its possible function but also adds further insight into the interplay between HIV-1 and its host at the cellular level. IMPORTANCE HIV-1, while now treatable, remains an important human pathogen causing significant morbidity and mortality globally. The virus predominantly infects CD4+ T cells and, if not treated with medication, ultimately causes their depletion, resulting in AIDS and death. Further refining our understanding of the interaction between HIV-1 and these cells has the potential to inform further therapeutic devel-opment. Previous studies have used transcriptomics to assess gene expression changes in CD4(+) T cells following HIV-1 infection; here, we provide a detailed exami-nation of changes occurring in the first 24 h of infection. Importantly, we define the viral protein Vpr as essential for the changes observed at this early stage. This find-ing has significance for understanding the role of Vpr in infection and pathogenesis and also for interpreting previous transcriptomic analyses of HIV-1 infection.

Automated summary

The interaction between HIV-1 and CD4(+) T cells have been studied through transcriptomics analysis, unveiling global changes in gene expression. The viral accessory protein Vpr plays a crucial role in these gene expression changes, highlighting its significance in infection and pathogenesis. This finding sheds new light on the interplay between HIV-1 and its host at the cellular level.