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5th International AIDS Society Conference on HIV Pathogenesis and TreatmentCape Town - July 19 - 22, 2009 |
ELEVATED TYPE I INTERFERON ACTIVITY IS ASSOCIATED WITH HIGH VIRAL LOAD AND LOW CD4 COUNT - ARE INTERFERON RESPONSES GOOD OR BAD IN HIV DISEASE?
IAS Conf HIV Pathog Treat 2009 Jul 19-22;5th: Abstract No. MOPEA001
S. Desai
1, X. Usuga1, K. Weber2, M. Cohen2,3, A. Landay1
1Rush University Medical Center, Department of Immunology/Microbiology, Chicago, United States, 2The CORE Center at John H. Stroger Jr Hospital of Cook County, Chicago, United States, 3Rush University Medical Center, Department of Medicine, Chicago, United States
BACKGROUND: Data on association of Interferon alpha (IFN-α) levels with microbial translocation lead us to hypothesize that IFN-α could turn on important genes in target cells that have pronounced effects on apoptosis and survival leading to immune activation. Here we report for the first time, type-I IFN activity in plasma samples from HIV infected individuals using a reporter cell assay.
METHODS: Comparisons of IFN activity were measured in 20 viremic HIV+ women (Viral Load (VL)>100,000 copies/mL), 10 aviremic HIV+ women on HAART (VL < 80 copies/mL), and 10 HIV uninfected women using reposited plasma from Chicago Women's Interagency HIV Study participants. IFN activity was assessed in human WISH epithelial cells for the capacity of type I IFN in plasma to induce expression of IFN-inducible genes (IFIG). WISH cells were cultured with media or 50% plasma for 6 hours. Real-time quantitative polymerase chain reaction was used to determine expression of IFIG's important in the apoptosis and survival pathways including PRKR, IFIT1, IFI44, and C1orf29 (preferentially induced by IFN-α). Analysis was performed using Kruskal-Wallis test and Spearman correlations.
RESULTS: Viremic HIV+ women had higher expression of IFI44, C1orf and IFIT1 genes compared to aviremic HIV+ and HIV uninfected women (mean fold increase in viremic>aviremic>uninfected 2.509, 0.769, 0.618 IFI44; 6.696,1.265,0.579 C1orf; 8.200, 0.905, 0.590 IFIT1) with strongest difference observed between HIV uninfected and viremic HIV+ women (p< 0.001 C1orf, IFIT1 and p<0.01IFI44). PRKR gene expression was not different between groups. In HIV+ viremic women, IFI44, C1orf and IFIT1 gene expression was significantly correlated with viral load (p<0.001, 0.01, 0.001 respectively) and inversely with CD4 counts (p<0.001, 0.0001, 0.0001 respectively).
CONCLUSIONS: Elevated type I interferon activity in plasma is associated with high viral load and low CD4 counts suggesting that activation of mediators of innate immune pathways may contribute to the pathogenesis of HIV disease.
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2009-07-22
MOPEA001
A8 - Innate immunity responses and function in natural history of HIV infection
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