The Landscape of IFN/ISG Signaling in HIV-1-Infected Macrophages and Its Possible Role in the HIV-1 Latency

Rojas, Masyelly; Luz‐Crawford, Patricia; Soto-Rifo, Ricardo; Reyes-Cerpa, Sebastián; Toro-Ascuy, Daniela

doi:10.3390/cells10092378

Cited by 11 publications

(11 citation statements)

References 168 publications

(246 reference statements)

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“…The innate immune system constitutes the first line of defense against pathogen infection, of which monocytes and macrophages are reported to be subverted by viruses for their spread and disease progression ( Baasch et al, 2021 ; Huang, 2021 ; Rojas et al, 2021 ). Investigating how host antiviral responses are launched and regulated might provide potential therapeutic targets for limiting viral infection and propagation.…”

Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation

Yang

Yong

et al. 2022

Front. Microbiol.

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As the global prototypical zoonotic hantavirus, Hantaan virus (HTNV) is prevalent in Asia and is the leading causative agent of severe hemorrhagic fever with renal syndrome (HFRS), which has profound morbidity and mortality. Macrophages are crucial components of the host innate immune system and serve as the first line of defense against HTNV infection. Previous studies indicated that the viral replication efficiency in macrophages determines hantavirus pathogenicity, but it remains unknown which factor manipulates the macrophage activation pattern and the virus-host interaction process. Here, we performed the transcriptomic analysis of HTNV-infected mouse bone marrow-derived macrophages and identified the long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1), especially the isoform NEAT1-2, as one of the lncRNAs that is differentially expressed at the early phase. Based on coculture experiments, we revealed that silencing NEAT1-2 hinders inflammatory macrophage activation and facilitates HTNV propagation, while enhancing NEAT1-2 transcription effectively restrains viral replication. Furthermore, sterol response element binding factor-2 (SREBP2), which controls the cholesterol metabolism process, was found to stimulate macrophages by promoting the production of multiple inflammatory cytokines upon HTNV infection. NEAT1-2 could potentiate SREBP2 activity by upregulating Srebf1 expression and interacting with SREBP2, thus stimulating inflammatory macrophages and limiting HTNV propagation. More importantly, we demonstrated that the NEAT1-2 expression level in patient monocytes was negatively correlated with viral load and HFRS disease progression. Our results identified a function and mechanism of action for the lncRNA NEAT1 in heightening SREBP2-mediated macrophage activation to restrain hantaviral propagation and revealed the association of NEAT1 with HFRS severity.

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Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation

Yang

Yong

et al. 2022

Front. Microbiol.

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“…It is true that chronic immune activation and sustained IFN‐I induction are associated with the generation of viral reservoirs during latency in HIV infection. 106 , 107 In chronic infection, persistently low levels of IFN‐I also contribute to the loss of CD4 + T cells and immune exhaustion. 101 , 108 Meanwhile, it is widely recognized that aberrant activation of IFN‐I is commonly detected in critical COVID‐19 patients; this aberrant activation leads to immune dysfunction and predicts a poor clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

SARS‐CoV‐2, HIV, and HPV: Convergent evolution of selective regulation of cGAS–STING signaling

Shen

Rui

Wang

et al. 2022

Journal of Medical Virology

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Recognizing aberrant cytoplasmic double‐stranded DNA and stimulating innate immunity is essential for the host's defense against viruses and tumors. Cyclic GMP–AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that synthesizes the second messenger 2′3′‐cGAMP and subsequently activates stimulator of interferon genes (STING)‐mediated activation of TANK‐binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) and the production of type I interferon (IFN‐I). Both the cGAS–STING‐mediated IFN‐I antiviral defense and the countermeasures developed by diverse viruses have been extensively studied. However, recent studies have revealed a convergent evolutionary feature of severe acute respiratory syndrome coronavirus 2 and human immunodeficiency virus (HIV) viral proteins in terms of the selective regulation of cGAS–STING‐mediated nuclear factor‐κB (NF‐κB) signaling without any effect on cGAS–STING‐mediated TBK1/IRF3 activation and IFN production. The potential beneficial effect of this cGAS–STING‐mediated, NF‐κB‐dependent antiviral effect, and the possible detrimental effect of IFN‐I in the pathogenesis of coronavirus disease 2019 and HIV infection deserve more attention and future investigation.

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“…They include 2′-5′-oligoadenylate synthetase (OAS), protein kinase R (PKR), ZAP, IFN-induced protein with tetratricopeptide repeats, ISG15, and members of the TRIM family. Furthermore, the release phase of the virus is inhibited by proteins, including viperin and tetherin ( 35 , 36 ). The SMAD4A can bind to the Smaug recognition region (SRE) sequence in the HBV virus sequence to trigger the degradation of the virus ( 37 ).…”

Section: Ifn Treatment For Hepatitis B Virus Infectionmentioning

confidence: 99%

Role of epigenetic modification in interferon treatment of hepatitis B virus infection

et al. 2022

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Human hepatitis B virus (HBV) is a small, enveloped DNA virus that causes acute and chronic hepatitis. Chronic hepatitis B (CHB) is associated with hepatocellular carcinoma pathogenesis. Interferons (IFNs) have been used for the treatment of CHB for a long time, with advantages including less treatment duration and sustained virological response. Presently, various evidence suggests that epigenetic modification of the viral covalently closed circular DNA (cccDNA) and the host genome is crucial for the regulation of viral activity. This modification includes histone acetylation, DNA methylation, N6-methyladenosine, and non-coding RNA modification. IFN treatment for CHB can stimulate multiple IFN-stimulated genes for inhibiting virus replication. IFNs can also affect the HBV life cycle through epigenetic modulation. In this review, we summarized the different mechanisms through which IFN-α inhibits HBV replication, including epigenetic regulation. Moreover, the mechanisms underlying IFN activity are discussed, which indicated its potential as a novel treatment for CHB. It is proposed that epigenetic changes such as histone acetylation, DNA methylation, m6A methylation could be the targets of IFN, which may offer a novel approach to HBV treatment.

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The Landscape of IFN/ISG Signaling in HIV-1-Infected Macrophages and Its Possible Role in the HIV-1 Latency

Cited by 11 publications

References 168 publications

LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation

LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation

SARS‐CoV‐2, HIV, and HPV: Convergent evolution of selective regulation of cGAS–STING signaling

Role of epigenetic modification in interferon treatment of hepatitis B virus infection

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