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

<h4>Background</h4>Interferon-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, therape...

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Autores principales:	Mohamed Abdel-Mohsen, Xutao Deng, Ali Danesh, Teri Liegler, Evan S Jacobs, Andri Rauch, Bruno Ledergerber, Philip J Norris, Huldrych F Günthard, Joseph K Wong, Satish K Pillai
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ad89e70fa2c7438db9ada3e0a10b0397
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spelling	oai:doaj.org-article:ad89e70fa2c7438db9ada3e0a10b03972021-11-25T05:58:08ZRole of microRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo.1932-620310.1371/journal.pone.0109220https://doaj.org/article/ad89e70fa2c7438db9ada3e0a10b03972014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0109220https://doaj.org/toc/1932-6203<h4>Background</h4>Interferon-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.<h4>Methods</h4>Global 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.<h4>Results</h4>miR-422a was the only miRNA significantly modulated by IFN-α/RBV in vivo (p<0.0001, paired t test; FDR<0.037). Our interactome mapping revealed extensive regulatory involvement of miR-422a in p53-dependent apoptotic and pyroptotic pathways. Based on sequence homology and inverse expression relationships, 29 unique miRNAs may regulate anti-HIV-1 restriction factor expression in vivo.<h4>Conclusions</h4>The 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.Mohamed Abdel-MohsenXutao DengAli DaneshTeri LieglerEvan S JacobsAndri RauchBruno LedergerberPhilip J NorrisHuldrych F GünthardJoseph K WongSatish K PillaiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e109220 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohamed Abdel-Mohsen Xutao Deng Ali Danesh Teri Liegler Evan S Jacobs Andri Rauch Bruno Ledergerber Philip J Norris Huldrych F Günthard Joseph K Wong Satish K Pillai Role of microRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo.
description	<h4>Background</h4>Interferon-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.<h4>Methods</h4>Global 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.<h4>Results</h4>miR-422a was the only miRNA significantly modulated by IFN-α/RBV in vivo (p<0.0001, paired t test; FDR<0.037). Our interactome mapping revealed extensive regulatory involvement of miR-422a in p53-dependent apoptotic and pyroptotic pathways. Based on sequence homology and inverse expression relationships, 29 unique miRNAs may regulate anti-HIV-1 restriction factor expression in vivo.<h4>Conclusions</h4>The 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.
format	article
author	Mohamed Abdel-Mohsen Xutao Deng Ali Danesh Teri Liegler Evan S Jacobs Andri Rauch Bruno Ledergerber Philip J Norris Huldrych F Günthard Joseph K Wong Satish K Pillai
author_facet	Mohamed Abdel-Mohsen Xutao Deng Ali Danesh Teri Liegler Evan S Jacobs Andri Rauch Bruno Ledergerber Philip J Norris Huldrych F Günthard Joseph K Wong Satish K Pillai
author_sort	Mohamed Abdel-Mohsen
title	Role of microRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo.
title_short	Role of microRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo.
title_full	Role of microRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo.
title_fullStr	Role of microRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo.
title_full_unstemmed	Role of microRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo.
title_sort	role of microrna modulation in the interferon-α/ribavirin suppression of hiv-1 in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ad89e70fa2c7438db9ada3e0a10b0397
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Role of microRNA modulation in the interferon-α/ribavirin suppression of HIV-1 in vivo.

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