Open Access Research

CD26/dipeptidyl peptidase IV (CD26/DPPIV) is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

Elijah M Songok123*, Bernard Osero1, Lyle Mckinnon34, Martin K Rono1, Winnie Apidi23, Elizabeth J Matey1, Adrienne FA Meyers235, Ma Luo235, Joshua Kimani23, Charles Wachihi3, Blake T Ball235, Frank A Plummer25 and Solomon Mpoke1

Author Affiliations

1 Centre For Virus Research, Mbagathi Road Kenya Medical Research Institute, Nairobi, Kenya

2 Department of Medical Microbiology, University of Manitoba,742 Bannatyne Avenue, Winnipeg, MB, Canada

3 University of Nairobi Institute of Tropical and Infectious Diseases (UNITID), Nairobi, Kenya

4 Department of Medicine, University of Toronto, Medical Sciences Building, 1 Kings College Circle, Toronto, ON M5S 1AB, Canada

5 National Microbiology Laboratories, Public Health Agency of Canada, 1015 Arlington Avenue, Winnipeg, MB, R3E 3RE, Canada

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Virology Journal 2010, 7:343  doi:10.1186/1743-422X-7-343

Published: 25 November 2010

Abstract

Background

Design of effective vaccines against the human immunodeficiency virus (HIV-1) continues to present formidable challenges. However, individuals who are exposed HIV-1 but do not get infected may reveal correlates of protection that may inform on effective vaccine design. A preliminary gene expression analysis of HIV resistant female sex workers (HIV-R) suggested a high expression CD26/DPPIV gene. Previous studies have indicated an anti-HIV effect of high CD26/DPPIV expressing cells in vitro. Similarly, high CD26/DPPIV protein levels in vivo have been shown to be a risk factor for type 2 diabetes. We carried out a study to confirm if the high CD26/DPPIV gene expression among the HIV-R were concordant with high blood protein levels and its correlation with clinical type 2 diabetes and other perturbations in the insulin signaling pathway.

Results

A quantitative CD26/DPPIV plasma analysis from 100 HIV-R, 100 HIV infected (HIV +) and 100 HIV negative controls (HIV Neg) showed a significantly elevated CD26/DPPIV concentration among the HIV-R group (mean 1315 ng/ml) than the HIV Neg (910 ng/ml) and HIV + (870 ng/ml, p < 0.001). Similarly a FACs analysis of cell associated DPPIV (CD26) revealed a higher CD26/DPPIV expression on CD4+ T-cells derived from HIV-R than from the HIV+ (90.30% vs 80.90 p = 0.002) and HIV Neg controls (90.30% vs 82.30 p < 0.001) respectively. A further comparison of the mean fluorescent intensity (MFI) of CD26/DPPIV expression showed a higher DPP4 MFI on HIV-R CD4+ T cells (median 118 vs 91 for HIV-Neg, p = 0.0003). An evaluation for hyperglycemia, did not confirm Type 2 diabetes but an impaired fasting glucose condition (5.775 mmol/L). A follow-up quantitative PCR analysis of the insulin signaling pathway genes showed a down expression of NFκB, a central mediator of the immune response and activator of HIV-1 transcription.

Conclusion

HIV resistant sex workers have a high expression of CD26/DPPIV in tandem with lowered immune activation markers. This may suggest a novel role for CD26/DPPIV in protection against HIV infection in vivo.