Role of microRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo

Autor: Andri Rauch, Xutao Deng, Joseph K. Wong, Mohamed Abdel-Mohsen, Evan S. Jacobs, Bruno Ledergerber, Teri Liegler, Satish K. Pillai, Huldrych F. Günthard, Philip J. Norris, Ali Danesh
Přispěvatelé: University of Zurich, Abdel-Mohsen, Mohamed
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: PLoS ONE, Vol 9, Iss 10, p e109220 (2014)
Wong, Joseph; Abdel-Mohsen, M; Deng, X; Danesh, A; Liegler, T; Jacobs, ES; et al.(2014). Role of MicroRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/168311k8
PLoS ONE
Abdel-Mohsen, Mohamed; Deng, Xutao; Danesh, Ali; Liegler, Teri; Jacobs, Evan S; Rauch, Andri; Ledergerber, Bruno; Norris, Philip J; Günthard, Huldrych F; Wong, Joseph K; Pillai, Satish K (2014). Role of MicroRNA Modulation in the Interferon-α/Ribavirin Suppression of HIV-1 In Vivo. PLoS ONE, 9(10), e109220. Public Library of Science 10.1371/journal.pone.0109220
ISSN: 1932-6203
Popis: BackgroundInterferon-α (IFN-α) 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-α 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-α-mediated suppression of HIV-1. To inform the development of novel miRNA-based antiretroviral strategies, we investigated the effects of exogenous IFN-α 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.MethodsGlobal miRNA expression was examined in longitudinal PBMC samples obtained from seven HIV/HCV-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated interferon-α/ribavirin therapy (IFN-α/RBV). We implemented novel hybrid computational-empirical approaches to characterize regulatory networks between miRNAs and anti-HIV-1 host restriction factors.ResultsmiR-422a was the only miRNA significantly modulated by IFN-α/RBV in vivo (pConclusionsThe specific reduction of miR-422a is associated with exogenous IFN-α treatment, and likely contributes to the IFN-α suppression of HIV-1 through the enhancement of anti-HIV-1 restriction factor expression and regulation of genes involved in programmed cell death. Moreover, our regulatory network analysis presents additional candidate miRNAs that may be targeted to enhance anti-HIV-1 restriction factor expression in vivo.
Databáze: OpenAIRE