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Pathogenesis and Immunity

Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo

Mohamed Abdel-Mohsen, Xutao Deng, Teri Liegler, John C. Guatelli, Mohamed S. Salama, Hussam El-din A. Ghanem, Andri Rauch, Bruno Ledergerber, Steven G. Deeks, Huldrych F. Günthard, Joseph K. Wong, Satish K. Pillai
Mohamed Abdel-Mohsen
aDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA
dFaculty of Science, Ain Shams University, Cairo, Egypt
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Xutao Deng
bBlood Systems Research Institute, San Francisco, California, USA
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Teri Liegler
aDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA
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John C. Guatelli
cUniversity of California, San Diego, La Jolla, California, and VA San Diego Healthcare System, San Diego, California, USA
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Mohamed S. Salama
dFaculty of Science, Ain Shams University, Cairo, Egypt
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Hussam El-din A. Ghanem
dFaculty of Science, Ain Shams University, Cairo, Egypt
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Andri Rauch
eDepartment of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland
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Bruno Ledergerber
fDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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Steven G. Deeks
aDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA
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Huldrych F. Günthard
fDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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Joseph K. Wong
aDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA
gDepartment of Medicine, San Francisco VA Medical Center, San Francisco, California, USA
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Satish K. Pillai
aDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA
bBlood Systems Research Institute, San Francisco, California, USA
gDepartment of Medicine, San Francisco VA Medical Center, San Francisco, California, USA
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DOI: 10.1128/JVI.02687-13
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    FIG 1

    IFN-α/riba induction of anti-HIV-1 restriction factors. (A) Fold induction in unfractionated PBMCs. (B) Fold induction in negatively selected CD4+ T cells. Values corresponding to fold induction during IFN-α/riba (green bars) and post-IFN-α/riba (red bars) treatment were normalized to the pretreatment expression level, as indicated by the dashed line. The mean and standard error are represented in each bar. Asterisks indicate statistically significant differences between the expression levels determined during and pretherapy based on a paired Wilcoxon test (* = P < 0.05; ** = P < 0.01).

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    FIG 2

    IFN-α/riba induction of cumulative restriction (CuRe) score to supraphysiologic levels correlates with viral load reduction. (A) Relationship between HIV-1 load reduction during IFN-α/riba therapy and CuRe score fold induction in PBMCs; no significant correlation was observed. (B) Relationship between HIV-1 load reduction during IFN-α/riba therapy and CuRe score fold induction in CD4+ T cells. Significance was assessed using Pearson's r correlation coefficient. (C) Comparison between CuRe scores of SHCS subjects undergoing IFN-α/riba therapy and of HIV-1-negative and HIV-1-infected (ART-naïve) viremic individuals enrolled in the SCOPE cohort. (D) Comparison of levels of expression of ISG15 (a marker of interferon exposure) between SHCS subjects undergoing IFN-α/riba therapy and HIV-1-negative and HIV-1-infected (ART-naïve) viremic individuals enrolled in the SCOPE cohort. Mann-Whitney tests were employed to determine significance.

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    Files in this Data Supplement:

    • Supplemental file 1 -

      Table S1 (SHCS subject characteristics at baseline (pre-IFN-α/riba treatment).)

      Table S2 (SCOPE cohort subject characteristics.)

      Table S3 (List of the 34 anti-HIV-1 host restriction factors measured by our CuRe Array.)

      Table S4 (Fold changes and statistical comparisons between treatment states.)

      Fig. S1 (Example of quantitative PCR analysis strategy.)

      Fig. S2 (Effect of IFN-α/riba therapy on HIV-1 viral load in plasma.)

      Fig. S3 (Nine IFN-α/riba-induced genes that exhibited significant correlation between fold induction and HIV-1 viral load reduction during IFN-α/riba therapy.)

      Fig. S4 (Comparison of the nine IFN-α/riba-induced genes that exhibited significant correlation between fold induction and HIV-1 viral load reduction during IFN-α/riba therapy from SHCS subjects during IFN-α/riba therapy and HIV-1-negative and HIV-1-infected (ART-untreated) viremic individuals enrolled in the SCOPE cohort.)

      Supplementary references.

      PDF, 1.5M

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Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo
Mohamed Abdel-Mohsen, Xutao Deng, Teri Liegler, John C. Guatelli, Mohamed S. Salama, Hussam El-din A. Ghanem, Andri Rauch, Bruno Ledergerber, Steven G. Deeks, Huldrych F. Günthard, Joseph K. Wong, Satish K. Pillai
Journal of Virology Dec 2013, 88 (1) 763-767; DOI: 10.1128/JVI.02687-13

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Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo
Mohamed Abdel-Mohsen, Xutao Deng, Teri Liegler, John C. Guatelli, Mohamed S. Salama, Hussam El-din A. Ghanem, Andri Rauch, Bruno Ledergerber, Steven G. Deeks, Huldrych F. Günthard, Joseph K. Wong, Satish K. Pillai
Journal of Virology Dec 2013, 88 (1) 763-767; DOI: 10.1128/JVI.02687-13
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