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Review
. 2022 May 10:13:902853.
doi: 10.3389/fimmu.2022.902853. eCollection 2022.

Antiviral Activities of Interleukin-27: A Partner for Interferons?

Heather Amsden  1 , Olena Kourko  1 , Madison Roth  1 , Katrina Gee  1
Affiliations
Review

Antiviral Activities of Interleukin-27: A Partner for Interferons?

Heather Amsden et al. Front Immunol. .

Abstract

Emergence of new, pandemic-level viral threats has brought to the forefront the importance of viral immunology and continued improvement of antiviral therapies. Interleukin-27 (IL-27) is a pleiotropic cytokine that regulates both innate and adaptive immune responses. Accumulating evidence has revealed potent antiviral activities of IL-27 against numerous viruses, including HIV, influenza, HBV and more. IL-27 contributes to the immune response against viruses indirectly by increasing production of interferons (IFNs) which have various antiviral effects. Additionally, IL-27 can directly interfere with viral infection both by acting similarly to an IFN itself and by modulating the differentiation and function of various immune cells. This review discusses the IFN-dependent and IFN-independent antiviral mechanisms of IL-27 and highlights the potential of IL-27 as a therapeutic cytokine for viral infection.

Keywords: antiviral immunity; infection; interferons; interleukin-27; viral immunology; virus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms of viral inhibition by IL-27. IFN-dependent: (A) IL-27 promotes the production of type I and III IFNs which leads to transcription of ISGs (, 23, 29). (B) IL-27 induced by type I IFNs leads to expression of TRIM25 (21). (C) IL-27 complexes with sIL-6R and increases production of type I and III IFNs, leading to transcription of several ISGs (31, 33, 34). (D) IL-27 promotes the production of type II IFN by T cells and NK cells (, , –54). (E) IL-27 promotes pDC differentiation, leading to increased IFN production (39). IFN-independent: (F) IL-27 directly promotes the transcription of several ISGs (19, 25, 27, 32, 38, 55). (G) IL-27 induces the expression of miRNAs that potentially target several viruses (56, 57). (H) IL-27 enhances the expression and signaling capacity of TLRs, which could influence recognition of PAMPs and DAMPs during viral infection (–15). (I) IL-27 increased pro-inflammatory cytokine and chemokine production (40). (J) IL-27 promotes IL-10 production by T cells to mediate immunopathology during viral infection (, , , , –61). (K) IL-27 enhances NK cell function by increasing granzyme B, RANTES, GM-CSF, and MIP-1α (28, 39).
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