A proteomic glimpse into the initial global epigenetic changes during HIV infection

Area of Science:

• Virology
• Epigenetics
• Molecular Biology

Background:

• HIV-1 replication involves integrating viral DNA into the host genome, altering chromatin and gene transcription.
• Histone post-translational modifications (PTMs) are crucial regulators of chromatin structure and gene expression.

Purpose of the Study:

• To correlate changes in histone PTM abundances with shifts in host transcriptional activity during HIV-1 infection.
• To investigate whether HIV-1 directly manipulates transcriptional machinery or if changes are host-mediated.

Main Methods:

• Time-course experiments using HIV-infected, UV-inactivated HIV-infected, and mock-infected SUP-T1 cells.
• Analysis of histone PTM profiles via nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Assessment of chromatin-associated enzyme expression (e.g., deacetylases, acetyltransferases, demethylases, methyltransferases, histone chaperones).

Main Results:

• Significant alterations in histone PTM abundances were observed, correlating with fluctuations in mRNA expression of chromatin enzymes.
• Few differences were found between HIV and UV-inactivated HIV (HIVUV) infections.
• Initial histone PTM changes appear to be host responses to infection rather than direct viral manipulation.

Conclusions:

• HIV-1 infection induces significant host-driven changes in histone PTMs and chromatin enzyme expression.
• These findings suggest that host responses to HIV-1 infection, rather than direct viral manipulation, drive early epigenetic alterations.
• This study provides a foundation for exploring targeted interventions in histone PTM-regulated HIV progression.