Pillai, S. K.Abdel-Mohsen, M.Guatelli, J.Skasko, M.Monto, A.Fujimoto, K.Yukl, S.Greene, W. C.Kovari, H.Rauch, A.Fellay, J.Battegay, M.Hirschel, B.Witteck, A.Bernasconi, E.Ledergerber, B.Gunthard, H. F.Wong, J. K.Barth, J.Battegay, M.Bernasconi, E.Boni, J.Bucher, H.Burton-Jeangros, C.Calmy, A.Cavassini, M.Cellerai, C.Egger, M.Elzi, L.Fehr, J.Fellay, J.Flepp, M.Francioli, P.Furrer, H.Fux, C.Gorgievski, M.Gunthard, H.Haerry, D.Hasse, B.Hirsch, H.Hirschel, B.Hosli, I.Kahlert, C.Kaiser, L.Keiser, O.Kind, C.Klimkait, T.Kovari, H.Ledergerber, B.Martinetti, G.Martinez De Tejada, B.Metzner, K.Muller, N.Nadal, D.Pantaleo, G.Rauch, A.Regenass, S.Rickenbach, M.Rudin, C.Schmid, P.Schultze, D.Schoni-Affolter, F.Schupbach, J.Speck, R.Taffe, P.Tarr, P.Telenti, A.Trkola, A.Vernazza, P.Weber, R.Yerly, S.2013-08-132013-08-132013-08-13201210.1073/pnas.1111573109https://infoscience.epfl.ch/handle/20.500.14299/94095The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro.Wesought to characterize the as-yet- undefinedrelationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log 10copies/mL in HIV/HCV-coinfected patients.APOBEC3G/3F andBST-2mRNAexpression was significantly elevated during IFN-á/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.text::journal::journal article::research article