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Review
. 2020;26(4):446-454.
doi: 10.2174/1381612826666200109181238.

Viral MicroRNAs: Interfering the Interferon Signaling

Imran Ahmad  1 , Araceli Valverde  1 , Hasan Siddiqui  1 , Samantha Schaller  1 , Afsar R Naqvi  1
Affiliations
Review

Viral MicroRNAs: Interfering the Interferon Signaling

Imran Ahmad et al. Curr Pharm Des. 2020.

Abstract

Interferons are secreted cytokines with potent antiviral, antitumor and immunomodulatory functions. As the first line of defense against viruses, this pathway restricts virus infection and spread. On the contrary, viruses have evolved ingenious strategies to evade host immune responses including the interferon pathway. Multiple families of viruses, in particular, DNA viruses, encode microRNA (miR) that are small, non-protein coding, regulatory RNAs. Virus-derived miRNAs (v-miR) function by targeting host and virus-encoded transcripts and are critical in shaping host-pathogen interaction. The role of v-miRs in viral pathogenesis is emerging as demonstrated by their function in subverting host defense mechanisms and regulating fundamental biological processes such as cell survival, proliferation, modulation of viral life-cycle phase. In this review, we will discuss the role of v-miRs in the suppression of host genes involved in the viral nucleic acid detection, JAK-STAT pathway, and cytokine-mediated antiviral gene activation to favor viral replication and persistence. This information has yielded new insights into our understanding of how v-miRs promote viral evasion of host immunity and likely provide novel antiviral therapeutic targets.

Keywords: JAK-STAT; Viruses; immune response; interferons; post-transcriptional silencing; viral microRNA..

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Figures

Fig. (1).
Fig. (1).. Mechanism of action of microRNA.
Viral miRNA biogenesis, similar to cellular miRNA, is dependent on the host miRNA machinery. Precursor vmiRs are generated in the nucleus and are exported to the cytoplasm. Pre-v-miRs are processed by Dicer and subsequently incorporated by Argonaute (AGO2)-associated miRNA-induced silencing complex (mi-RISC). Mature, single stranded, v-miR binds to cognate mRNA harboring complementary sequences. Viral miRNA guides host RNA endonuclease Argonaute (AGO2)-associated mi-RISC to either enhance degradation or suppress translation of target (host or viral) transcripts.
Fig. (2).
Fig. (2).. Activation of interferon pathway can potently restrict and clear virus.
Interferon pathway is an innate immune response activated by virusinfected cells. Recognition of virus-derived factors or replication intermediates (nucleic acids) can actívate host signaling cascade that can induce production of interferons. These secreted molecules act in paracrine (and autocrine) manner to actívate neighboring cells to induce antiviral state.
Fig. (3).
Fig. (3).. Strategies employed by virus to modulate host antiviral response.
Viruses have evolved multiple strategies to evade or block antiviral response generated by host. Virus infection leads to global changes in host transcriptome (miRnome and mRNAs). Many viruses secrete cytokine homologs, which modulate immune response. Viral suppressors of RNAi (VSRs) are viral proteins which interfere with host miRNA biogenesis. Virally encoded miRNAs (V-miRs) target and downregulate many immune related host genes. Viral proteins suppress inflammation by targeting inflammatory cytokines.
Fig. (4).
Fig. (4).. Viral miRNAs target genes involved in interferon signaling pathway.
The infected cell detects the viral PAMPs by various pattern recognition receptors (PRRs) such as RIG-I and trigger the secretion of interferons. Once secreted, the interferons bind to their receptor and stimulates the expression of hundreds of interferon stimulated genes (ISGs), which coordinate to achieve an antiviral state by cell. Various viral miRNAs (shown in red) block different genes of interferon pathway.
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