Antiviral Immunity and Circular RNA: No End in Sight

Cadena, Cristhian; Hur, Sun

doi:10.1016/j.molcel.2017.07.005

Cited by 42 publications

(37 citation statements)

References 8 publications

(20 reference statements)

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“…We also identified several cirRNAs which can serve as miRNA sponges and are crucial regulators of gene expression 38 . Some circRNAs present antiviral activity, interacting directly with the antiviral genes DDX58 (RIG-I), IFIH1 (MDA5) and TLR3 39 . The major class of non-coding lncRNAs also shows antiviral activity and involvement in cell proliferation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Zika virus targets the human thymic epithelium

Messias

Loss-Morais

Carvalho

et al. 2020

Sci Rep

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Previous work showed that the thymus can be infected by RNA viruses as HIV and HTLV-1. We thus hypothesized that the thymus might also be infected by the Zika virus (ZIKV). Herein we provide compelling evidence that ZIKV targets human thymic epithelial cells (TEC) in vivo and in vitro. ZIKVinfection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, ZIKV modulates a high amount of coding RNAs with upregulation of genes related to cell adhesion and migration, as well as non-coding genes including miRNAs, circRNAs and lncRNAs. Moreover, we observed enhanced attachment of lymphoblastic T-cells to infected TEC, as well as virus transfer to those cells. Lastly, alterations in thymuses from babies congenitally infected were seen, with the presence of viral envelope protein in TEC. Taken together, our data reveals that the thymus, particularly the thymic epithelium, is a target for the ZIKV with changes in the expression of molecules that are relevant for interactions with developing thymocytes. Zika virus (ZIKV) epidemics in 2015-2016 resulted in devastating effects, causing microcephaly, other related congenital defects at birth and neurodevelopmental delay after two years in children born from mothers infected by the virus during pregnancy 1-4. Additionally, ZIKV infection in adults correlated with a rise in the frequency of cases of Guillain-Barré syndrome 5,6. Although the knowledge on the cellular and molecular alterations caused by the ZIKV in the nervous tissue largely increased in the last few years 2,7,8 , the effects of this virus upon hematopoietic tissues are much less defined. In terms of secondary lymphoid organs, ZIKV RNA and protein have been described in lymph nodes of Rhesus monkeys in both paracortex and germinal centers 9,10. The virus was also found in macrophages, dendritic cells, and B-cells, in both spleen and axillary lymph nodes of this non-human primate. However, in the same study, the presence of ZIKV RNA in T-cells was observed only in axillary lymph nodes from one animal 10. Much less is known on the putative infection of primary lymphoid organs, and more particularly in the thymus. This central lymphoid organ is responsible for the generation of T lymphocytes under the control of the thymic microenvironment, a three-dimensional cellular network mainly composed by thymic epithelial cells-TEC 11. In this respect, it is interesting to note the thymus as a target organ for other RNA viruses, such as HIV 12 and HTLV-1 13,14. In fact, we showed that cultured human TEC can be infected by HTLV-1 and convey virus particles to lymphoblastic T cells 15,16. We thus hypothesized that the thymic epithelium might also be infected by the Zika virus. Herein we provide compelling evidence that ZIKV targets human TEC both in vivo and in vitro. Data are provided showing that ZIKV-infection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, in vitro data revealed that the virus could modulate a high amount ...

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Section: Discussionmentioning

confidence: 99%

Zika virus targets the human thymic epithelium

Messias

Loss-Morais

Carvalho

et al. 2020

Sci Rep

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“…NF90/ NF110 promotes circRNA processing by stabilizing the flanking intronic RNA pairs in the nucleus and subsequently interacts with the mature circRNA to form the NF90/NF110-circRNA complex (circRNPs) in the cytoplasm. Upon viral infection, NF90/NF110 is released from the circRNPs, resulting in an antiviral immune response (Cadena and Hur, 2017;Li et al, 2017) ( Figure 3E).…”

Section: Circrnas Are Involved In Innate Immune Responsesmentioning

confidence: 99%

“…Some specific circRNAs encode peptides (Legnini et al, 2017;Zhang et al, 2018), but internal ribosome entry site (IRES) elements might be necessary for this (Tatomer and Wilusz, 2017;Yun et al, 2017). Furthermore, recent work has shown that circRNAs may play critical roles in innate immune pathways (Cadena and Hur, 2017;Chen et al, 2017) Although models of regulation are well established in many species, tissues, and cells types, the functions of linear lncRNAs and circRNAs remain elusive. Here, we highlight advances in our understanding of the multiple structures, functions, and regulation of linear lncRNAs and circRNAs.…”

Section: Introductionmentioning

confidence: 99%

Structure, Regulation, and Function of Linear and Circular Long Non-Coding RNAs

Qin

Zhang

2020

Front. Genet.

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Long non-coding RNAs (lncRNAs), including linear lncRNAs and circular RNAs (circRNAs), exhibit a surprising range of structures. Linear lncRNAs and circRNAs are generated by different pathways. Linear lncRNAs perform functions that depend on their specific sequences, transcription, and DNA elements of their gene loci. In some cases, linear lncRNAs contain a short open reading frame encoding a peptide. circRNAs are covalently closed RNAs with tissue-specific and cell-specific expression patterns that have recently been extensively investigated. Pioneering work focusing on their biogenesis and functional characterization indicates that circRNAs regulate cell development via multiple mechanisms and play critical roles in the immune system. Furthermore, circRNAs in exosomes function on target cells. As with linear lncRNAs, specific circRNAs can also be translated. In this review, we summarize current understanding and highlight the diverse structure, regulation, and function of linear lncRNAs and circRNAs.

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“…Innate immune response plays a significant role in early response to viral and other infections. Viral infections are recognised through variety of pattern recognition receptors (PRRs) which include Toll-like receptor 3 (TLR3), retinoic acid-inducible gene-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics, physiology 2 (LGP2) [48], [49] and oligoadenylate synthetase-like (OASL) [25]. It was shown that purified circRNAs activates RIG-I and confers effective immune protection against viral infection [26].…”

Section: Circrnas Involved In Antiviral Immunitymentioning

confidence: 99%

Functions and Implications of Circular RNAs in Antiviral Immunity

Hassan¹

2019

AiM

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In addition to mature mRNAs, splicing of pol II transcripts generates numerous other RNAs including circular RNAs (circRNAs). circRNAs are a group of transcripts generated by non-sequential back splicing or forward splicing of exons, introns or a combination of both from a donor to an acceptor target. This forms covalently closed RNA molecule i.e. without free 5' end caps or 3' Poly (A) tails thereby making them more stable than their linear counterparts. Though they are recognized as part of non-coding RNAs, long noncoding precisely; evidence of translations has been reported from these molecules. circRNAs are considered emerging new members of the gene regulatory family. These circRNAs have several potential modes of action, some of which serve as microRNAs sponges shown in Table 1, protein binding RNAs, cellular transports, transcriptional regulators and modulating immune system. Viral circRNAs may evade immune recognition by many proposed mechanisms. These include undergoing slicing by host splicing machinery, being single stranded lacking free 5' and 3' ends, having miRNA sponge function, convenient regulatory functions which include initiating lytic replication, etc. Pattern of expression of these circRNAs differs from healthy individuals to different stages of viral infectious diseases. Thus, their use as potential biomarkers for diagnostics and future therapeutics targets have been proposed, especially with regards to viral infections that seem impossible for the human immune system to totally eliminate like the Epstein-Barr viral infection. So, this review summarizes the functions and implications of circRNAs regarding antiviral immunity.

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Antiviral Immunity and Circular RNA: No End in Sight

Cited by 42 publications

References 8 publications

Zika virus targets the human thymic epithelium

Zika virus targets the human thymic epithelium

Structure, Regulation, and Function of Linear and Circular Long Non-Coding RNAs

Functions and Implications of Circular RNAs in Antiviral Immunity

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