Role of retroviral restriction factors in the interferon-α-mediated suppression of HIV-1 in vivo

摘要: The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number studies have suggested that induction apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies IFN-α-mediated suppression HIV-1 replication in vitro. We sought to characterize as-yet-undefined relationship between treatment, factors, vivo. APOBEC3G, APOBEC3F, BST-2 expression levels were measured HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naive individuals before, during, after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased viral load by -0.921 (±0.858) log(10) copies/mL HIV/HCV-coinfected patients. APOBEC3G/3F was significantly elevated during treatment patient-derived CD4+ T cells (P < 0.04 P 0.008, paired Wilcoxon), extent correlated with reduction 0.05, Pearson's r). APOBEC3 degree hypermutation 0.03, Spearman's ρ), evolution accessory protein U (Vpu) suggestive increased BST-2-mediated selection pressure. These data suggest host play a critical role capacity vivo, warrant investigation into therapeutic strategies specifically enhance these intrinsic immune HIV-1-infected individuals.