Chromosome 1 variants associated with decreased HIV set-point viral load correlate with PRKAB2 expression changes

Area of Science:

• Genetics
• Immunology
• Virology

Background:

• A prior study identified a genomic region on chromosome 1 associated with reduced human immunodeficiency virus type 1 (HIV) set-point viral load, implicating CHD1L.
• Regulatory variants can affect the expression of multiple genes in a region, necessitating further investigation into other genes near CHD1L.

Purpose of the Study:

• To evaluate the genetic regulation of PRKAB2, located upstream of CHD1L.
• To determine the downstream impacts of PRKAB2 regulation on HIV pathogenesis.

Main Methods:

• Utilized genotype and gene expression data from the Gene Expression Omnibus (GEO) repository and Genotype-Tissue Expression (GTEx) database.
• Performed cell-type-specific correlation analyses between CHD1L and PRKAB2 expression.
• Conducted functional analyses using PRKAB2 knockout induced pluripotent stem cells.

Main Results:

• Observed cell-type-specific correlations between CHD1L and PRKAB2 expression (positive in whole blood, negative in monocytes).
• Found significantly reduced PRKAB2 expression in individuals with HIV set-point viral load-associated variants.
• Demonstrated that PRKAB2 loss-of-function influences CHD1L expression and genes involved in immune signaling pathways relevant to HIV infection.

Conclusions:

• Genetic variants associated with HIV set-point viral load impact multiple genes, including PRKAB2.
• Altered PRKAB2 expression influences critical immune signaling processes, contributing to HIV pathogenesis.
• These findings highlight the role of host genetics in HIV pathogenesis and suggest new targets for functional studies.