Idiosyncrasies of Viral Noncoding RNAs Provide Insights into Host Cell Biology

Withers, John; Mondol, Vanessa; Pawlica, Paulina; Rosa-Mercado, Nicolle A.; Tycowski, Kazimierz T.; Ghasempur, S.; Torabi, Seyed Fakhreddin; Steitz, Joan A.

doi:10.1146/annurev-virology-092818-015811

Cited by 23 publications

(23 citation statements)

References 155 publications

(174 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Viruses have been known to express their own non-coding RNAs. Some of these earlier discoveries included HSV’s (Herpes simplex virus) latency-associated transcript (LAT), EBV (Epstein–Barr virus) -encoded small RNAs (EBERs), and KSHV’s (Kaposi’s sarcoma herpesvirus) polyadenylated nuclear (PAN) RNA ( Withers et al, 2019 ; Tagawa et al, 2020 ), which would now be called lncRNAs (long non-coding RNAs). Studying the functions of these viral lncRNAs was challenging since they do not code for proteins.…”

Section: Introductionmentioning

confidence: 99%

Characterizing Expression and Regulation of Gamma-Herpesviral Circular RNAs

Tagawa

Santos

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

Multiple herpesviruses have been recently found to encode viral circular RNAs. Like cellular circular RNAs, these RNAs lack poly-A tails and their 5′ and 3′ ends have been joined, which confers protection from RNA exonucleases. We examined the expression patterns of circular RNAs from Kaposi’s sarcoma herpesvirus (KSHV) in various environments. We performed deep sequencing of circRNA-enriched total RNA from a KSHV-positive patient lymph node for comparison with previous circRNA-Seq results. We found that circvIRF4 is highly expressed in the KSHV-positive patient sample relative to both B cell lines and de novo infected primary vascular and lymphatic endothelial cells (LECs). Overall, this patient sample showed a viral circRNA expression pattern more similar to the pattern from B cell lines, but we also discovered new back-spliced junctions and additional viral circular RNAs in this patient sample. We validated some of these back-spliced junctions as circular RNAs with standard assays. Differential expression patterns of circular RNAs in different cell types led us to investigate what cellular factors might be influencing the ratio of viral linear mRNAs to circular RNAs. We found that repression of certain RNA-binding proteins shifted the balance between viral linear mRNAs and circular RNAs. Taken together, examining viral circular RNA expression patterns may become useful tools for discovering their functions, the regulators of their expression, and determining the stage and cell types of infection in humans.

show abstract

Section: Introductionmentioning

confidence: 99%

Characterizing Expression and Regulation of Gamma-Herpesviral Circular RNAs

Tagawa

Santos

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…However, it is known that a number of viral miRNAs are produced through noncanonical pathways. ( 52 ), for example, miRNAs encoded by murine gammaherpesvirus 68 (MHV68), in which the precursor miRNAs are located in a tRNA-like structure ( 53 ). Despite this variety of biogenesis pathways, miRNAs are required to be loaded into an Ago protein in order to function.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Functional Small Noncoding RNA of African Swine Fever Virus

Dunn

Ivens

Netherton

et al. 2020

J Virol

View full text Add to dashboard Cite

African swine fever virus (ASFV) causes a lethal haemorrhagic disease of domestic pigs, against which there is no vaccine available. ASFV has a large, double-stranded DNA genome that encodes over 150 proteins. Replication takes place predominantly in the cytoplasm of the cell and involves complex interactions with host cellular components including small non-coding RNAs (sncRNAs). A number of DNA viruses are known to manipulate sncRNA either by encoding their own or disrupting host sncRNA. In order to investigate the interplay between ASFV and sncRNAs, a study of host and viral small RNAs extracted from ASFV-infected primary porcine macrophages (PAMs) was undertaken. We discovered that ASFV infection had only a modest effect on host miRNAs, with only 6 miRNAs differentially expressed during infection. The data also revealed 3 potential novel small RNAs encoded by ASFV, ASFVsRNA1-3. Further investigation of ASFVsRNA2 detected it in lymphoid tissue from pigs with ASF. Overexpression of ASFVsRNA2 led to up to a 1 log reduction in ASFV growth indicating that ASFV utilises a virally-encoded small RNA to disrupt its own replication. IMPORTANCE African swine fever (ASF) poses a major threat to pig populations and food security worldwide. The disease is endemic in Africa and Eastern Europe and rapidly emerging into Asia where it has led to the deaths of over a million pigs in the last 12 months. The development of safe and effective vaccines to protect pigs against ASF has been hindered by lack of understanding of the complex interactions between ASFV and the host cell. We focused our work on characterising the interactions between ASFV and sncRNAs. Although comparatively modest changes to host sncRNA abundances were observed upon ASFV infection, we discovered and characterised a novel functional ASFV-encoded sncRNA. The results from this study add important insights into ASFV host-pathogen interactions. This knowledge may be exploited to develop more effective ASFV vaccines that take advantage of the sncRNA system.

show abstract

“…Since ncRNAs are not presented via Major histocompatibility complex (MHC), they result to be non-immunogenic to the adaptive immune system and thus particularly useful tools for viruses to influence host cell functions [25]. Interestingly, viruses produce v-ncRNAs capable of controlling not only the expression of viral genes, but also influence host cell regulation and evade host innate and specific immune responses, crucial mechanisms in the viral pathogenetic processes [9]. Humans are equipped of pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), retinoic acid-inducible gene-I (RIG-1), and protein kinase R (PKR), that are able to detect foreign nucleic acids, as viral RNAs [24].…”

Section: Viral Immune Evasion Strategiesmentioning

confidence: 99%

“…As an example, viral-derived dsRNA induce the activation of both dsRNA dependent-PKR and TLRs, which results in type I IFN response, a well-known anti-viral defense mechanism [26]. Different v-ncRNAs, like EBV's Epstein-Barr virus-encoded small RNAs (EBERs), adenoviral VAI and VAII, and HIV's trans-activation response RNA (TAR) act as a trap to inhibit PKR activation [9]. The inhibition of IFN production is one of the most important strategies developed by viruses to block antiviral response.…”

Section: Viral Immune Evasion Strategiesmentioning

confidence: 99%

“…It has been postulated that since the viral genome is size-limited, any non-coding space is rationated [8]. Recently, thanks to the novel high-throughput RNA sequencing techniques it has been discovered that many, but not all viruses genome express non-coding RNAs (ncRNAs) for their own benefit [9]. According to the Baltimore classification (first defined in 1971), viruses are divided into seven categories depending on the nucleic acid (DNA or RNA), strandedness (single-stranded or double-stranded), sense, and method of replication [10].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Non-Coding RNAs: Strategy for Viruses’ Offensive

Gallo

Bulati

Miceli

et al. 2020

ncRNA

View full text Add to dashboard Cite

The awareness of viruses as a constant threat for human public health is a matter of fact and in this resides the need of understanding the mechanisms they use to trick the host. Viral non-coding RNAs are gaining much value and interest for the potential impact played in host gene regulation, acting as fine tuners of host cellular defense mechanisms. The implicit importance of v-ncRNAs resides first in the limited genomes size of viruses carrying only strictly necessary genomic sequences. The other crucial and appealing characteristic of v-ncRNAs is the non-immunogenicity, making them the perfect expedient to be used in the never-ending virus-host war. In this review, we wish to examine how DNA and RNA viruses have evolved a common strategy and which the crucial host pathways are targeted through v-ncRNAs in order to grant and facilitate their life cycle.

show abstract

Idiosyncrasies of Viral Noncoding RNAs Provide Insights into Host Cell Biology

Cited by 23 publications

References 155 publications

Characterizing Expression and Regulation of Gamma-Herpesviral Circular RNAs

Characterizing Expression and Regulation of Gamma-Herpesviral Circular RNAs

Identification of a Functional Small Noncoding RNA of African Swine Fever Virus

Non-Coding RNAs: Strategy for Viruses’ Offensive

Contact Info

Product

Resources

About