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

Area of Science:

• Virology and Immunology
• Molecular Biology
• Genomics

Background:

• Viral infections trigger complex host-pathogen interactions, often altering host gene expression.
• Genome-wide transcriptomics is a powerful tool for studying these cellular responses.
• Previous studies on human immunodeficiency virus type 1 (HIV-1) in CD4+ T cells lack detailed early-stage infection analysis.

Purpose of the Study:

• To analyze host gene expression changes in primary CD4+ T cells during the first 48 hours of HIV-1 infection.
• To identify the role of the viral accessory protein Vpr in early HIV-1-induced transcriptional alterations.

Main Methods:

• Transcriptomic analysis of primary CD4+ T cells at multiple time points (4.5, 8, 12, 24, and 48 hours) post-HIV-1 infection.
• Comparison of gene expression profiles in the presence and absence of the viral protein Vpr.

Main Results:

• Global host gene expression changes were observed as early as 4.5 hours post-infection.
• Upregulation of innate immunity, cytokine production, and apoptosis genes, and downregulation of transcription/translation genes were identified.
• The viral accessory protein Vpr was essential for most gene expression changes at 12 and 48 hours post-infection.

Conclusions:

• HIV-1 rapidly manipulates host gene expression in CD4+ T cells, initiating within hours of infection.
• The viral protein Vpr plays a critical role in mediating these early transcriptional changes.
• Understanding these early interactions, particularly the role of Vpr, is vital for developing new therapeutic strategies against HIV-1.