Antiretroviral activity of pegylated interferon alfa-2a in patients co-infected with HIV/hepatitis C virus

Marucco, D. Aguilar; Veronese, Lorenzo; Requena, Daniel González de; Bonora, Stefano; Calcagno, Andrea; Cavecchia, Ilaria; Sinicco, Alessandro; Rosa, Francesco Giuseppe De; Castaldo, Giuseppe; Perri, Giovanni Di

doi:10.1093/jac/dkl497

Cited by 11 publications

(4 citation statements)

References 9 publications

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“…S2 in the supplemental material). This effect is consistent with previous IFN-␣/riba and IFN-␣ monotherapy studies (4,5,7,8). Seven of 15 individuals were included in analyses of PBMC gene expression, and the remaining eight individuals were included in analyses of CD4 ϩ T cell gene expression.…”

supporting

confidence: 78%

“…Induction of IFN-␣ expression is a critical first step in the defense against a range of viral infections (1,2). The antiretroviral activity of IFN-␣ was demonstrated in vitro soon after the discovery of HIV-1 (3), and several studies have reported that exogenous IFN-␣ treatment potently suppresses HIV-1 in vivo (4)(5)(6)(7)(8). Moreover, IFN-␣ therapy was recently associated with significant reduction in the size of the HIV-1 latent reservoir (9), suggesting that interferon-associated pathways may be exploited to achieve HIV-1 eradication.…”

mentioning

confidence: 99%

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Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo

Abdel‐Mohsen

Deng

Liegler

et al. 2014

J Virol

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supporting

confidence: 78%

mentioning

confidence: 99%

Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo

Abdel‐Mohsen

Deng

Liegler

et al. 2014

J Virol

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“…The antiretroviral activity of the IFN-α cytokine was demonstrated in vitro almost immediately after the discovery of HIV-1, and includes inhibition of HIV-1 reverse transcription, viral assembly, and virion release (26). IFN-α has been reported to suppress HIV-1 viremia in chronically infected individuals (27)(28)(29), and is known to induce APOBEC3 and BST-2 expression in a number of tissues and cell types in vitro (7,(30)(31)(32). However, to date, no data describe the effects of exogenous IFN-α treatment on the expression of these restriction factors in vivo, and the relevance of these factors to virologic control in chronically infected individuals is unknown.…”

mentioning

confidence: 99%

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

Pillai

Abdel‐Mohsen²,

Guatelli³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

109

115

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

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“…Induction of interferon-α (IFN-α) expression is a critical first step in the defense against a range of viral pathogens [1] , [2] . Several studies have demonstrated that IFN-α treatment potently suppresses HIV-1 viremia in chronically infected individuals [3] – [6] . A provocative recent report demonstrated that IFN-α treatment results in sustained viral suppression in the absence of antiretroviral therapy (ART) and significant reduction in the size of the HIV-1 reservoir in chronically-infected individuals [7] , [8] .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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 (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.ConclusionsThe 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.

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Antiretroviral activity of pegylated interferon alfa-2a in patients co-infected with HIV/hepatitis C virus

Abstract: A significant early anti-HIV activity of PEG-IFN alfa-2a was observed. Such an effect warrants further clinical evaluation in the management of co-infected patients.

Cited by 11 publications

References 9 publications

Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo

Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo

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

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

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