Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• Host restriction factors are crucial for innate antiviral defense against pathogens like HIV-1.
• Identifying specific host factors that control HIV-1 replication in vivo is essential for understanding viral pathogenesis and developing interventions.

Purpose of the Study:

• To identify host factors associated with HIV-1 control during acute infection using single-cell transcriptomic analysis.
• To investigate the role of prothymosin alpha (PTMA) as a potential HIV-1 restriction factor.

Main Methods:

• Single-cell RNA sequencing was employed to correlate host gene expression with intracellular viral RNA levels in infected cells.
• Genome-wide association analysis identified significant inverse correlations between PTMA expression and viral RNA transcription.
• In vitro experiments were conducted to validate the inhibitory effect of PTMA on HIV-1 transcription and production.

Main Results:

• A significant inverse correlation was observed between prothymosin alpha (PTMA) gene expression and intracellular HIV-1 RNA levels.
• This association was validated across diverse patient cohorts with different HIV-1 subtypes (CRF01_AE and subtype B).
• Overexpression of PTMA in vitro demonstrated its ability to inhibit HIV-1 transcription and infectious virus production.

Conclusions:

• Prothymosin alpha (PTMA) is identified as a novel host factor that restricts HIV-1 infection in vivo.
• The findings have significant implications for understanding HIV-1 transmission dynamics.
• This discovery opens new avenues for developing therapeutic strategies targeting PTMA for HIV-1 cure.