HIV-Induced Epigenetic Alterations in Host Cells.

Area of Science:

• Virology
• Epigenetics
• Immunology

Background:

• Human immunodeficiency virus (HIV) establishes lifelong infections by integrating its genome into host cells.
• HIV's proviral DNA is regulated by host epigenetic machinery, influencing viral latency and reactivation.
• HIV infection alters host cell epigenotypes, impacting gene expression and cellular function.

Purpose of the Study:

• To investigate the role of host epigenetic regulators in controlling HIV latency and reactivation.
• To explore how HIV proteins influence the host cell epigenotype and gene expression.
• To identify potential epigenetic modifying compounds for curative HIV therapy.

Main Methods:

• Analysis of chromatin state near the viral promoter (5' LTR).
• Assessment of DNA methyltransferase (DNMT) activity and DNA methylation patterns.
• Evaluation of epigenetic drug targets, including histone deacetylase inhibitors (HDACI) and DNA methyltransferase inhibitors (DNMTI).

Main Results:

• HIV-1 infection upregulates DNMT activity and induces hypermethylation in CD4(+) T cells.
• Demethylation of the FOXP3 promoter observed in HIV-infected patients' tissues, potentially due to DNMT1 downregulation.
• HIV proteins modulate host cell epigenetics, affecting gene expression.

Conclusions:

• Epigenetic modifications play a critical role in HIV latency and reactivation.
• Targeting epigenetic regulators offers a potential strategy for HIV cure.
• Combination therapy with antiretrovirals and epigenetic modifiers may reactivate latent HIV-1 genomes.