Role of MicroRNA Modulation in the Interferon- alpha /Ribavirin Suppression of HIV-1 In Vivo: e109220

Background Interferon- alpha (IFN- alpha ) treatment suppresses HIV-1 viremia and reduces the size of the HIV-1 latent reservoir. Therefore, investigation of the molecular and immunologic effects of IFN- alpha may provide insights that contribute to the development of novel prophylactic, therapeutic and curative strategies for HIV-1 infection. In this study, we hypothesized that microRNAs (miRNAs) contribute to the IFN- alpha -mediated suppression of HIV-1. To inform the development of novel miRNA-based antiretroviral strategies, we investigated the effects of exogenous IFN- alpha treatment on global miRNA expression profile, HIV-1 viremia, and potential regulatory networks between miRNAs and cell-intrinsic anti-HIV-1 host factors in vivo. Methods Global miRNA expression was examined in longitudinal PBMC samples obtained from seven HIV/HCV-coinfected, antiretroviral therapy-naive individuals before, during, and after pegylated interferon- alpha /ribavirin therapy (IFN- alpha /RBV). We implemented novel hybrid computational-empirical approaches to characterize regulatory networks between miRNAs and anti-HIV-1 host restriction factors. Results miR-422a was the only miRNA significantly modulated by IFN- alpha /RBV in vivo (p