Murine Hepatitis Virus Exoribonuclease nsp14 Is Required for the Biogenesis of Viral Circular RNAs

Yang, Shaomin; Cruz-Cosme, Ruth; Cao, Di; Zhou, Hong; Wu, Songbin; Huang, Jia-Bin; Luo, Zhen; Zhu, Hua; Tang, Qiyi

doi:10.1128/spectrum.04460-22

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…CircRNAs have been identified from multiple types of cell lines, tissues, and organs in humans and demonstrated to be associated with different diseases. Recent research has revealed a repertoire of circRNAs derived from viruses, including DNA viruses (EBV, KSHV, HPV, HCMV, and MDV) 18 – 21 , 25 – 27 and RNA viruses (SARS-CoV-2, SARS-CoV, MERS-CoV, and Murine Hepatitis Virus, MHV) 28 , 41 . Our presented studies are unique because we applied deep circRNA sequencing to landscape circRNAs in VZV-infected SH-SY5Y cells and tissues of herpes zoster patients that were then experimentally confirmed.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of Varicella Zoster Virus circular RNA in lytic infection

Yang,

Cao,

Jaijyan

et al. 2024

Nat Commun

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This study investigates the role of circular RNAs (circRNAs) in the context of Varicella-Zoster Virus (VZV) lytic infection. We employ two sequencing technologies, short-read sequencing and long-read sequencing, following RNase R treatment on VZV-infected neuroblastoma cells to identify and characterize both cellular and viral circRNAs. Our large scanning analysis identifies and subsequent experiments confirm 200 VZV circRNAs. Moreover, we discover numerous VZV latency-associated transcripts (VLTs)-like circRNAs (circVLTslytic), which contain multiple exons and different isoforms within the same back-splicing breakpoint. To understand the functional significance of these circVLTslytic, we utilize the Bacteria Artificial Chromosome system to disrupt the expression of viral circRNAs in genomic DNA location. We reveal that the sequence flanking circVLTs’ 5’ splice donor plays a pivotal role as a cis-acting element in the formation of circVLTslytic. The circVLTslytic is dispensable for VZV replication, but the mutation downstream of circVLTslytic exon 5 leads to increased acyclovir sensitivity in VZV infection models. This suggests that circVLTslytic may have a role in modulating the sensitivity to antiviral treatment. The findings shed new insight into the regulation of cellular and viral transcription during VZV lytic infection, emphasizing the intricate interplay between circRNAs and viral processes.

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Section: Discussionmentioning

confidence: 99%

Identification and characterization of Varicella Zoster Virus circular RNA in lytic infection

Yang,

Cao,

Jaijyan

et al. 2024

Nat Commun

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“…There is evidence that other RNA viruses, such as SARS coronaviruses (29)(30)(31) and the Bombyx mori reovirus (26,32) accumulate RNA species that contain non-contiguous viral sequences. In those studies, selected junction sequences were demonstrated by RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Virus-derived circular RNAs populate hepatitis C virus–infected cells

Cao,

Boonchuen,

Chen

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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It is known that pre-mRNAs in eukaryotic cells can be processed to circular RNAs by a backsplicing mechanism. Circular RNAs have great stability and can sequester proteins or small RNAs to exert functions on cellular pathways. Because viruses often exploit host pathways, we explored whether the RNA genome of the cytoplasmic hepatitis C virus is processed to yield virus-derived circRNAs (vcircRNAs). Computational analyses of RNA-seq experiments predicted that the viral RNA genome is fragmented to generate hundreds of vcircRNAs. More than a dozen of them were experimentally verified by rolling-circle amplification. VcircRNAs that contained the viral internal ribosome entry site were found to be translated into proteins that displayed proviral functions. Furthermore, two highly abundant, nontranslated vcircRNAs were shown to enhance viral RNA abundance. These findings argue that novel vcircRNA molecules modulate viral amplification in cells infected by a cytoplasmic RNA virus.

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“…CircRNAs can function as microRNA (miRNA) sponges, regulate of parental gene expression, and even serve as translation templates [ 522 , 523 ]. They have also been identified from DNA virus-infected cells, such as Epstein–Barr virus (EBV) [ 524 , 525 , 526 , 527 ], Kaposi Sarcoma herpesvirus (KSHV) [ 525 , 528 , 529 , 530 ], human papillomaviruses (HPVs) [ 531 ] and RNA viruses, severe acute respiratory disease coronavirus 2 (SARS-CoV-2) [ 532 ] and murine hepatitis virus (MHV) [ 533 ]. This suggests that circRNAs may play important roles in the viral life cycle and infection processes.…”

Section: Hcmv Circular Rnas (Circrnas)mentioning

confidence: 99%

Insights into the Transcriptome of Human Cytomegalovirus: A Comprehensive Review

Zeng

Cao

Yang

et al. 2023

Viruses

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Human cytomegalovirus (HCMV) is a widespread pathogen that poses significant risks to immunocompromised individuals. Its genome spans over 230 kbp and potentially encodes over 200 open-reading frames. The HCMV transcriptome consists of various types of RNAs, including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs), with emerging insights into their biological functions. HCMV mRNAs are involved in crucial viral processes, such as viral replication, transcription, and translation regulation, as well as immune modulation and other effects on host cells. Additionally, four lncRNAs (RNA1.2, RNA2.7, RNA4.9, and RNA5.0) have been identified in HCMV, which play important roles in lytic replication like bypassing acute antiviral responses, promoting cell movement and viral spread, and maintaining HCMV latency. CircRNAs have gained attention for their important and diverse biological functions, including association with different diseases, acting as microRNA sponges, regulating parental gene expression, and serving as translation templates. Remarkably, HCMV encodes miRNAs which play critical roles in silencing human genes and other functions. This review gives an overview of human cytomegalovirus and current research on the HCMV transcriptome during lytic and latent infection.

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Murine Hepatitis Virus Exoribonuclease nsp14 Is Required for the Biogenesis of Viral Circular RNAs

Cited by 7 publications

References 18 publications

Identification and characterization of Varicella Zoster Virus circular RNA in lytic infection

Identification and characterization of Varicella Zoster Virus circular RNA in lytic infection

Virus-derived circular RNAs populate hepatitis C virus–infected cells

Insights into the Transcriptome of Human Cytomegalovirus: A Comprehensive Review

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