Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon

Greenwell-Wild, Teresa; Vázquez, Nancy; Jin, Wenwen; Rangel, Zoila G.; Munson, Peter J.; Wahl, Sharon M.

doi:10.1182/blood-2009-03-211540

Cited by 89 publications

(106 citation statements)

References 51 publications

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“…2), an increased serum level of IL-32 might result in the acceleration of HIV-1 replication or spread in vivo. Recently, IL-27 has been shown to inhibit HIV-1 replication in macrophages (38,39). Interestingly, we found that M-CSF also significantly reduced the anti-HIV-1 activity of IL-27 (data not shown).…”

Section: Discussionmentioning

confidence: 61%

M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

Osman

Bhuyan

Hashimoto

et al. 2014

The Journal of Immunology

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M-CSF promotes the differentiation and survival of macrophages, and preferentially induces anti-inflammatory M2, rather than proinflammatory M1 macrophages. Recently, another cytokine, IL-32, was also shown to promote macrophage differentiation. In this article, we provide the first evidence, to our knowledge, that M-CSF has both additive and inhibitory effects on the macrophage-related activities of IL-32. When added to M-CSF–derived macrophages, M-CSF and IL-32 promoted macrophage survival, which was further enhanced by their combination. However, they had different effects on HIV-1 replication; that is, it was stimulated by M-CSF and inhibited by IL-32. Interestingly, the anti–HIV-1 activity of IL-32 was counteracted by M-CSF. Such inhibitory effect of M-CSF was not observed with IL-32–induced M1-like features including high cytokine/chemokine production and strong expression of the costimulatory molecule CD80. However, IL-32–treated macrophages unexpectedly showed also M2-like features including increased phagocytic activity, and high expression of CD14 and the scavenger receptor CD163, and the expression of CD14 and CD163 was further upregulated by cotreatment with M-CSF. The findings of this study regarding the unique functional interplay between M-CSF and IL-32 increase our understanding of the mechanisms that regulate the survival and M1/M2 ratio of macrophages, as well as HIV-1 replication in macrophages.

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Section: Discussionmentioning

confidence: 61%

M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

Osman

Bhuyan

Hashimoto

et al. 2014

The Journal of Immunology

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“…Treatment of monocytes and T cells with IL‐27 induces BST‐2 in an IFN signaling‐independent manner 154. IL‐27 is a cytokine produced by myeloid cells 155 and functions to inhibit HIV‐1 replication in various cell types 156, 157, 158. Whether BST‐2 is one of the effectors of anti‐HIV‐1 activity of IL‐27 is yet to be determined.…”

Section: Bst‐2 Regulationmentioning

confidence: 99%

The role of BST‐2/Tetherin in host protection and disease manifestation

Mahauad‐Fernandez

Okeoma

2015

Immunity, Inflammation and Disease

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Host cells respond to viral infections by activating immune response genes that are not only involved in inflammation, but may also predispose cells to cancerous transformation. One such gene is BST‐2, a type II transmembrane protein with a unique topology that endows it tethering and signaling potential. Through this ability to tether and signal, BST‐2 regulates host response to viral infection either by inhibiting release of nascent viral particles or in some models inhibiting viral dissemination. However, despite its antiviral functions, BST‐2 is involved in disease manifestation, a function linked to the ability of BST‐2 to promote cell‐to‐cell interaction. Therefore, modulating BST‐2 expression and/or activity has the potential to influence course of disease.

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“…Our results showed that IL-27 represses the expression of HBV proteins and the replication of HBV capsid-associated DNA in HepG2.2.15, HepG2, and Huh7 cells in a dose-dependent fashion, suggesting that IL-27 plays an inhibitory role in HBV replication. IL-27 was reported to exhibit antiviral activity by inhibiting replication of HIV and HCV (12,13) and to produce IFN-inducible antiviral proteins by eliciting a type I IFN-like response (51,52), in which IFN-a initially binds to the type I IFN receptor, IFNAR1/2, and induces the phosphorylation of STAT1/2 and the expression of ISGs, which, in turn, initiate an antiviral state in target cells.…”

Section: Il-27 Enhances the Expression Of Ifn-l1 Receptors Il-28r1 Anmentioning

confidence: 99%

“…IL-27 is a heterodimeric anti-inflammatory cytokine composed of EBI3 and p28, which regulates Th cell function during autoimmune and pathogen-induced immune responses (1,3,4). IL-27 exhibits various therapeutic capabilities, such as regulating antiviral ability (12,13), enhancing antitumor immune responses (14), directing antiproliferative effects on tumors (15)(16)(17), and reducing the inflammation associated with experimental autoimmune arthritis (18,19). Serum IL-27 triggers an earlier immune response to prevent hepatic injury in different clinical-pathologic stages of HBV-infected patients (50).…”

Section: Il-27 Enhances the Expression Of Ifn-l1 Receptors Il-28r1 Anmentioning

confidence: 99%

“…Overexpressing IL-27 decreases regulatory T cell frequencies, induces spontaneous inflammation, and activates proliferation of naive human B cells and CD4 + T cells (10,11). IL-27 has therapeutic potential through various mechanisms: inhibiting replication of HIV (12) and hepatitis C virus (HCV) (13), enhancing antitumor immune responses (14), directing antiproliferative effects on tumors (15)(16)(17), and reducing the inflammation associated with experimental autoimmune arthritis (18,19). We recently demonstrated that during influenza A virus (IAV) infection, IL-27 is strongly induced through cyclooxygenase-2 (COX-2)-and protein kinase A (PKA)-signaling pathways (20).…”

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confidence: 99%

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IL-27, a Cytokine, and IFN-λ1, a Type III IFN, Are Coordinated To Regulate Virus Replication through Type I IFN

Cao

Zhang

et al. 2014

The Journal of Immunology

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IL-27, a member of the IL-12 family, plays a critical role in the control of innate and adaptive immune responses. IFN-λ1, a member of the type III IFN family, shows antiviral abilities. In this study, we investigated the effects of IL-27 and IFN-λ1 on the replication of hepatitis B virus (HBV), a major pathogen associated with a high risk for cirrhosis, liver failure, and hepatocellular carcinoma. We revealed that HBV infection activates IL-27 expression and IFN-λ1 production and demonstrated that viral-activated IL-27 and IFN-λ1 are coordinated to inhibit HBV replication. Initially, HBV infection upregulates IL-27 expression, which, in turn, stimulates IFN-λ1 production through regulating ERK1/2 signaling and by enhancing NF-κB nuclear translocation to bind to the IFN-λ1 promoter. Moreover, IL-27–activated IFN-λ1 upregulates IFN-λ1 receptor (IL-28R1 and IL-10Rβ) activity, resulting in the activation of the STAT1/2 pathway, which, in turn, induces the expression of IFN-stimulated genes, including IFN-inducible dsRNA-activated protein kinase, oligoadenylate synthetase 1, and IFN-induced GTP-binding protein 1 and, finally, inhibits HBV protein expression and viral capsid–associated DNA replication. More interestingly, we also revealed that type I IFN (IFN-α) is also involved in the downregulation of HBV replication mediated by IL-27. Thus, we identified a previously unknown mechanism by which IL-27 and IFN-λ1 are coordinated to regulate virus replication through type I IFN.

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Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon

Abstract: Infection of CD4

Cited by 89 publications

References 51 publications

M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

The role of BST‐2/Tetherin in host protection and disease manifestation

IL-27, a Cytokine, and IFN-λ1, a Type III IFN, Are Coordinated To Regulate Virus Replication through Type I IFN

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