Role of MicroRNA Modulation in the Interferon-α/Ribavirin Suppression of HIV-1 In Vivo

摘要: BACKGROUND Interferon-α (IFN-α) treatment suppresses HIV-1 viremia and reduces the size of latent reservoir. Therefore, investigation molecular immunologic effects IFN-α may provide insights that contribute to development novel prophylactic, therapeutic curative strategies for infection. In this study, we hypothesized microRNAs (miRNAs) IFN-α-mediated suppression HIV-1. To inform miRNA-based antiretroviral strategies, investigated exogenous on global miRNA expression profile, viremia, potential regulatory networks between miRNAs cell-intrinsic anti-HIV-1 host factors in vivo. METHODS Global was examined longitudinal PBMC samples obtained from seven HIV/HCV-coinfected, therapy-naive individuals before, during, after pegylated interferon-α/ribavirin therapy (IFN-α/RBV). We implemented hybrid computational-empirical approaches characterize restriction factors. RESULTS miR-422a only significantly modulated by IFN-α/RBV vivo (p<0.0001, paired t test; FDR<0.037). Our interactome mapping revealed extensive involvement miR-422a p53-dependent apoptotic pyroptotic pathways. Based sequence homology inverse relationships, 29 unique regulate factor vivo. CONCLUSIONS The specific reduction is associated with treatment, likely contributes through enhancement regulation genes involved programmed cell death. Moreover, our network analysis presents additional candidate be targeted enhance vivo.