The Cellular and Viral circRNAome Induced by Respiratory Syncytial Virus Infection

Yao, Wenqian; Pan, Jinghui; Liu, Zhaoyu; Dong, Zhijie; Liang, Min; Shu, Xiaoyan; Xiao, Yao; Cai, Xiaodan; Peng, Tao; Zhou, Xinke; Cai, Hua

doi:10.1128/mbio.03075-21

Cited by 17 publications

(17 citation statements)

References 45 publications

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“…In-depth sequence analyses of each back-splicing site revealed the production of canonical and noncanonical viral circRNAs processed by the U2-dependent or U2-independent splicing machinery, respectively. Therefore, this report provides new information on the production of noncanonical circRNAs during viral infection ( 6 , 25 , 26 ). The next set of experiments was based on open and unbiased analyses of lymphoma-derived sequences over the whole MDV genome and pointed out the meq and LATs loci as the central hubs of viral circRNA expression during tumorigenesis.…”

Section: Discussionmentioning

confidence: 94%

“…However, only a few viruses have been shown to encode their circRNAs. Most of the viral circRNAs have been identified in the Herpesviridae family ( 6 , 21 , 22 ) but some circRNAs are produced by other DNA virus families, such as the Papillomaviridae ( 23 ) and Polyomaviridae ( 24 ) or RNA viruses, e.g., Coronaviridae ( 25 ) or Paramyxoviridae ( 26 ). Former functional studies on herpesvirus-encoded circRNAs have suggested roles in immune evasion and cancer development ( 27 – 29 ).…”

Section: Introductionmentioning

confidence: 99%

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Marek’s Disease Virus Virulence Genes Encode Circular RNAs

Chasseur

Trozzi

Istasse

et al. 2022

J Virol

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Marek’s Disease Virus Virulence Genes Encode Circular RNAs

Chasseur

Trozzi

Istasse

et al. 2022

J Virol

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“…CircRNAs are an alternative splicing product and thus expand the number of transcripts without extending genome size; a strategy that may be advantageous for organisms with limited coding space. In line with this hypothesis, recent studies have experimentally confirmed viral circRNAs expressed by beta-and gamma-herpesviruses, human papillomavirus, Merkel cell polyomavirus, hepatitis B virus, respiratory syncytial virus, and coronaviruses; with bioinformatic evidence for many other viruses (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 79%

Noncanonical circRNA biogenesis driven by alpha and gamma herpesviruses

Dremel

Kopardé

Arbuckle

et al. 2022

Preprint

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Herpesviruses express over 100 transcripts, including messenger RNAs, long noncoding RNAs, and microRNAs. Herein, we add to this list by performing circular RNA (circRNA) profiling for Herpes Simplex Virus-1, Kaposi sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68. Using cell culture and animal models of lytic and latent infection, we identified thousands of back-splicing variants. This included circRNAs derived from viral latency genes (circK12, circLAT). During lytic infection circRNAs tiled the viral genome, with a transcriptional density 4,500-fold greater than the host. We characterized cis- and trans-elements controlling back-splicing and found that lytic infection promoted rampant, sequence-independent back-splicing. Using eCLIP and 4SU-Sequencing, we determined that the KSHV RNA binding protein (ORF57) preferentially bound viral circRNAs and globally promoted accumulation post-transcriptionally. Our work elucidates a unique splicing mechanism driven by late lytic replication and identifies a class of transcripts with potential to function in replication, persistence, or tumorigenesis.

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“…Currently, research on viral circRNAs is primarily focused on DNA viruses. Only a few RNA viruses have been reported to produce circRNAs, including respiratory syncytial virus, 26 MERS-CoV, 27 SARS-CoV-1, 27 SARS-CoV-2, 27 Bombyx mori cypovirus (BmCPV), 28 murine hepatitis virus, 29 and grass carp reovirus. 30 Among the aforementioned RNA viruses that can produce circRNAs, only the function of the BmCPV circRNA has been revealed.…”

Section: Introductionmentioning

confidence: 99%

Influenza A virus H1N1-derived circNP37 positively regulates viral replication by sponging host miR-361-5p

Zhu,

Wang,

et al. 2023

Preprint

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SummaryRNA viruses, such as respiratory syncytial virus and SARS-CoV-2, can generate viral circular RNAs (circRNAs), which may play important roles during viral infection. However, whether influenza A viruses have this ability to generate viral circRNAs remains unknown. In this study, we discovered that the negative-strand RNA of the H1N1 nucleoprotein (NP) gene can generate a circRNA, designated circNP37. Furthermore, we demonstrated that circNP37 positively regulated viral replication by competitively sponging host miR-361-5p which inhibited polymerase basic protein 2 (PB2) expression. These results were confirmed using in vivo experiments. Compared with wild-type virus, infection with circNP37 knockout virus resulted in a reduced viral load in the lungs. This study demonstrates, for the first time, the existence and biological function of H1N1-derived circNP37. These findings help us better understand the mechanisms of influenza virus replication and pathogenicity.HighlightsNegative-strand RNA of the H1N1 nucleoprotein gene can generate a circRNACircNP37 plays important roles in viral replication and viral-host interactionsCircNP37 positively regulates replication by competitively sponging host miR-361-5peTOC BlurbIn this study, we found that influenza A virus H1N1 infection can generate virus-derived circRNA, circNP37. We also demonstrated that circNP37 positively regulate viral PB2 gene expression and viral replication via sponge host miR-361-5p during viral infection.

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The Cellular and Viral circRNAome Induced by Respiratory Syncytial Virus Infection

Abstract: Noncoding RNAs (ncRNAs) demonstrate substantial roles in cell-virus interactions. Circular RNAs (circRNAs) are a newly identified class of ncRNAs that have gained increased attention recently.

Cited by 17 publications

References 45 publications

Marek’s Disease Virus Virulence Genes Encode Circular RNAs

Marek’s Disease Virus Virulence Genes Encode Circular RNAs

Noncanonical circRNA biogenesis driven by alpha and gamma herpesviruses

Influenza A virus H1N1-derived circNP37 positively regulates viral replication by sponging host miR-361-5p

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