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


CONCLUSIONS
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.
Centre For Virus Research, Mbagathi Road Kenya Medical Research Institute, Nairobi, Kenya. Songok@cc.umanitoba.ca
Elijah M
EM
Songok
Bernard
B
Osero
Lyle
L
McKinnon
Martin K
MK
Rono
Winnie
W
Apidi
Elizabeth J
EJ
Matey
Adrienne F A
AF
Meyers
Ma
M
Luo
Joshua
J
Kimani
Charles
C
Wachihi
Blake T
BT
Ball
Frank A
FA
Plummer
Solomon
S
Mpoke
D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis / Q000097:blood*; D005260:Female; D020869:Gene Expression Profiling; D006678:HIV / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016328:NF-kappa B / Q000096:biosynthesis; D011477:Sex Work
D016328:NF-kappa B; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4