Transcriptomic Analysis Reveals Key Pathways Influenced by HIV-2 Vpx.

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Viral protein X (Vpx) is an accessory protein in HIV-2 and SIV.
• Known functions include counteracting SAMHD1 and aiding viral complex translocation.
• Its effects on the cellular transcriptome and cytokine environment are not fully understood.

Purpose of the Study:

• To investigate the impact of HIV-2 Vpx on cellular gene expression and cytokine secretion.
• To analyze the effects of wild-type and functionally restricted Vpx proteins.

Main Methods:

• Transcriptomic analysis of THP-1 cells using vectors expressing wild-type and K68-R70 Vpx.
• Validation and quantification of differentially expressed genes via real-time quantitative PCR (qPCR).
• Analysis of cytokine secretion in transfected cell media and confirmation with replication-competent virions.

Main Results:

• HIV-2 Vpx significantly alters genes involved in helicases, zinc finger proteins, chaperones, transcription factors, and DNA methylation.
• Affected genes regulate viral processes, type I interferon signaling, DNA transcription, and innate immune response.
• Vpx decreases HIV-1 Tat expression and induces proinflammatory cytokines.

Conclusions:

• HIV-2 Vpx profoundly impacts the host cell transcriptome and cytokine milieu.
• Vpx manipulates the cellular environment to facilitate viral infection.
• Findings offer insights into the complex role of Vpx in viral pathogenesis.