Systemic DPP4/CD26 is associated with natural HIV-1 control: Implications for COVID-19 susceptibility

Abstract

The current intersection of the COVID-19 and HIV-1 pandemics, has raised concerns about the risk for poor COVID-19 outcomes particularly in regions like sub-Saharan Africa, disproportionally affected by HIV. DPP4/CD26 has been suggested to be a potential therapeutic target and a biomarker for risk in COVID-19 patients with high risk co-morbidities. We therefore evaluated soluble DPP4 (sDPP4) levels and activity in plasma of 131 HIV-infected and 20 HIV-uninfected South African individuals. Flow cytometry was performed to compare cell surface expression of DPP4/CD26 and activation markers on peripheral blood mononuclear cells of extreme clinical phenotypes. Progressors had lower specific DPP4 activity and lower frequency of CD3⁺ T-cells expressing CD26 than HIV-1 controllers, but more activated CD3⁺CD26⁺ T-cells. The frequency of CD26-expressing T-cells negatively correlated with HLA-DR⁺ and CD38⁺ T-cells. Divergent DPP4/CD26 expression between HIV-1 controllers and progressors may have implications for risk and treatment of COVID-19 in people living with HIV.

Keywords: CD26; COVID-19; DPP4; Elite controllers; HIV-1; Progressors.

Graphical abstract

Fig. 1

Characterization of sDPP4 levels activity in HIV-1 infection. (A) sDPP4 levels (B) total DPP4 activity and (C) specific DPP4 activity were measured in HIV-1 uninfected healthy controls (HC) and HIV infected group. Box-whisker plots depict the median (horizontal black line), 25th and 75th percentile (margins of the box) and the 5th and 95th percentiles (whiskers). Dots represent outliers.

Fig. 2

Analysis of DPP4 activity in HIV controllers and progressors. Comparisons between HIV-1 uninfected healthy controls (HCs) and the HIV-1 infected subgroups; HIV-1 controllers (HICs) and progressors were performed for (A) total DPP4 activity and (B) specific DPP4 activity. (C) Total DPP4 activity and (D) specific DPP4 activity were compared amongst the HIC subgroups; elite controllers (ECs), viraemic controllers (VCs) and high viral load long term non-progressors (HVL LTNPs) and between the progressors. Box-whisker plots depict the median (horizontal black line), 25th and 75th percentile (margins of the box) and the 5th and 95th percentiles (whiskers). Dots represent outliers.

Fig. 3

Correlation between specific DPP4 activity, HIV-1 viral load and CD4 counts. (A) Specific DPP4 activity inversely correlated with HIV-1 viral load and (B) positively correlated with CD4 counts.

Fig. 4

Relationship between T-cell activation and CD26 expression in elite controllers and progressors. (A) Frequency of CD3⁺CD26⁺ T-cells, CD4⁺CD26⁺ T-cells and CD8⁺CD26⁺ T-cells were compared amongst HIV-1 uninfected healthy controls (HCs) (n = 5), elite controllers (ECs) (n = 5) and progressors (n = 6). Percentage of (B) CD3⁺CD26⁺HLA-DR⁺ T-cells, CD4⁺CD26⁺HLA-DR⁺ T-cells and CD8⁺CD26⁺HLA-DR⁺ T-cells were compared amongst HCs (n = 5), ECs (n = 5) and progressors (n = 6). Box-whisker plots depict the median (horizontal black line), 25th and 75th percentile (margins of the box) and the min and max (whiskers). Dots represent all individuals. Correlation analysis was performed with all samples (n = 16) between frequency of CD3⁺CD26⁺ T-cells and (C) CD3⁺HLA-DR⁺ T-cells and (D) CD3⁺CD38⁺ T-cells.