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Amplifying and Quantifying HIV-1 RNA in HIV Infected Individuals with Viral Loads Below the Limit of Detection by Standard Clinical Assays
Published on: September 26, 2011
HIV elite control is associated with reduced TRAILshort expression.
Ana C Paim1, Nathan W Cummins1, Sekar Natesampillai1
1Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota.
HIV-1 elite controllers show lower levels of TRAILshort, a protein that can inhibit cell death. This reduced TRAILshort expression may contribute to their ability to control HIV-1 infection.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apoptosis plays a role in CD4 T-cell death and HIV-1 control.
- TRAILshort, a splice variant, acts as a dominant-negative inhibitor of TRAIL-induced cell death in HIV-1 infection.
- HIV-1 elite controllers naturally suppress viral replication through mechanisms not fully understood.
Purpose of the Study:
- To investigate the association between HIV-1 elite controller status and TRAILshort expression levels.
- To determine if reduced TRAILshort expression is a factor in the immune control observed in elite controllers.
Main Methods:
- A cohort study compared TRAILshort and full-length TRAIL expression in HIV-1 elite controllers and viremic progressors.
- Gene and protein expression levels were quantified using RNA-seq, antibody bead array, and proximity extension assays in PBMCs and plasma.
Main Results:
- HIV-1 elite controllers exhibited significantly lower TRAILshort transcript levels in peripheral blood mononuclear cells (PBMCs) compared to viremic progressors (P=0.002).
- Plasma TRAILshort protein levels were also significantly reduced in elite controllers relative to viremic progressors (P<0.001).
Conclusions:
- Reduced expression of TRAILshort in both PBMCs and plasma is significantly associated with HIV-1 elite controller status.
- These findings suggest that lower TRAILshort levels may contribute to the immune control of HIV-1 replication in elite controllers.
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