Direct and indirect effects of CYTOR lncRNA regulate HIV gene expression

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Antiretroviral therapy (ART) controls Human Immunodeficiency Virus (HIV) but cannot eliminate the viral reservoir.
• Non-coding RNAs (ncRNAs) role in HIV gene expression and latency is under-explored.
• Understanding host factors regulating HIV is crucial for developing a cure.

Purpose of the Study:

• To investigate the role of non-coding RNAs in HIV gene expression and latency.
• To identify novel host factors that regulate HIV reactivation from latency.
• To explore the function of the Cytoskeleton Regulator (CYTOR) long non-coding RNA (lncRNA) in HIV infection.

Main Methods:

• Identification and characterization of CYTOR lncRNA.
• Functional studies involving T cell stimulation and HIV-infected cells.
• Analysis of CYTOR binding to the HIV promoter and association with P-TEFb.
• Assessment of CYTOR's impact on actin polymerization and HIV gene expression.
• Treatment with pharmacological inhibitors of actin polymerization.

Main Results:

• CYTOR lncRNA is upregulated upon T cell stimulation and activates HIV gene expression.
• CYTOR directly binds to the HIV promoter and activates viral transcription via P-TEFb.
• CYTOR regulates cellular actin dynamics, and its depletion impairs actin polymerization.
• Inhibition of actin polymerization reduces HIV gene expression.

Conclusions:

• CYTOR lncRNA acts as a crucial regulator of HIV gene expression and viral latency.
• CYTOR contributes to HIV reactivation through both direct and indirect mechanisms involving actin dynamics.
• Targeting CYTOR or actin polymerization pathways may offer new therapeutic strategies against HIV latency.