scholarly journals Extreme Genomic CpG Deficiency in SARS-CoV-2 and Evasion of Host Antiviral Defense

2020 ◽  
Vol 37 (9) ◽  
pp. 2699-2705 ◽  
Author(s):  
Xuhua Xia
Keyword(s):  
Mammalian Species ◽  
Viral Rna ◽  
Rna Modification ◽  
Specific Expression ◽  
New Host ◽  
Cpg Dinucleotides ◽  
Viral Genomes ◽  
Canine Coronavirus ◽  
Cellular Environment ◽  
Cpg Deficiency

Abstract Wild mammalian species, including bats, constitute the natural reservoir of betacoronavirus (including SARS, MERS, and the deadly SARS-CoV-2). Different hosts or host tissues provide different cellular environments, especially different antiviral and RNA modification activities that can alter RNA modification signatures observed in the viral RNA genome. The zinc finger antiviral protein (ZAP) binds specifically to CpG dinucleotides and recruits other proteins to degrade a variety of viral RNA genomes. Many mammalian RNA viruses have evolved CpG deficiency. Increasing CpG dinucleotides in these low-CpG viral genomes in the presence of ZAP consistently leads to decreased viral replication and virulence. Because ZAP exhibits tissue-specific expression, viruses infecting different tissues are expected to have different CpG signatures, suggesting a means to identify viral tissue-switching events. The author shows that SARS-CoV-2 has the most extreme CpG deficiency in all known betacoronavirus genomes. This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression. A survey of CpG deficiency in viral genomes identified a virulent canine coronavirus (alphacoronavirus) as possessing the most extreme CpG deficiency, comparable with that observed in SARS-CoV-2. This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG. Thus, viral surveys focused on decreasing CpG in viral RNA genomes may provide important clues about the selective environments and viral defenses in the original hosts.

scholarly journals Persistent Human Papillomavirus Infection

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 321
Author(s):  
Ashley N. Della Fera ◽  
Alix Warburton ◽  
Tami L. Coursey ◽  
Simran Khurana ◽  
Alison A. McBride
Keyword(s):  
Human Papillomavirus ◽  
Dna Replication ◽  
Cellular Proliferation ◽  
Basal Cells ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Viral Genomes ◽  
Cellular Environment ◽  
E6 And E7 ◽  
Cellular Replication

Persistent infection with oncogenic human papillomavirus (HPV) types is responsible for ~5% of human cancers. The HPV infectious cycle can sustain long-term infection in stratified epithelia because viral DNA is maintained as low copy number extrachromosomal plasmids in the dividing basal cells of a lesion, while progeny viral genomes are amplified to large numbers in differentiated superficial cells. The viral E1 and E2 proteins initiate viral DNA replication and maintain and partition viral genomes, in concert with the cellular replication machinery. Additionally, the E5, E6, and E7 proteins are required to evade host immune responses and to produce a cellular environment that supports viral DNA replication. An unfortunate consequence of the manipulation of cellular proliferation and differentiation is that cells become at high risk for carcinogenesis.

scholarly journals Reovirus Low-Density Particles Package Cellular RNA

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1096
Author(s):  
Timothy W. Thoner ◽  
Xiang Ye ◽  
John Karijolich ◽  
Kristen M. Ogden
Keyword(s):  
Rna Polymerase ◽  
Viral Proteins ◽  
Viral Rna ◽  
Low Density ◽  
Rna Packaging ◽  
Genome Packaging ◽  
Double Stranded Rna ◽  
Viral Genomes ◽  
Mammalian Orthoreovirus ◽  
Insight Into

Packaging of segmented, double-stranded RNA viral genomes requires coordination of viral proteins and RNA segments. For mammalian orthoreovirus (reovirus), evidence suggests either all ten or zero viral RNA segments are simultaneously packaged in a highly coordinated process hypothesized to exclude host RNA. Accordingly, reovirus generates genome-containing virions and “genomeless” top component particles. Whether reovirus virions or top component particles package host RNA is unknown. To gain insight into reovirus packaging potential and mechanisms, we employed next-generation RNA-sequencing to define the RNA content of enriched reovirus particles. Reovirus virions exclusively packaged viral double-stranded RNA. In contrast, reovirus top component particles contained similar proportions but reduced amounts of viral double-stranded RNA and were selectively enriched for numerous host RNA species, especially short, non-polyadenylated transcripts. Host RNA selection was not dependent on RNA abundance in the cell, and specifically enriched host RNAs varied for two reovirus strains and were not selected solely by the viral RNA polymerase. Collectively, these findings indicate that genome packaging into reovirus virions is exquisitely selective, while incorporation of host RNAs into top component particles is differentially selective and may contribute to or result from inefficient viral RNA packaging.

scholarly journals Rearrangements of intranuclear structures involved in RNA processing in response to adenovirus infection

1994 ◽  
Vol 107 (6) ◽  
pp. 1457-1468 ◽  
Author(s):  
F. Puvion-Dutilleul ◽  
J.P. Bachellerie ◽  
N. Visa ◽  
E. Puvion
Keyword(s):  
Rna Processing ◽  
Rna Splicing ◽  
Specific Binding ◽  
Viral Rna ◽  
Nuclear Transformation ◽  
Adenovirus Infection ◽  
Storage Site ◽  
Single Stranded Dna ◽  
Viral Genomes ◽  
Interchromatin Granules

We have studied in HeLa cells at the electron microscope level the response to adenovirus infection of the RNA processing machinery. Components of the spliceosomes were localized by in situ hybridization with biotinylated U1 and U2 DNA probes and by immunolabeling with Y12 anti-Sm monoclonal antibody, whereas poly(A)+ RNAs were localized by specific binding of biotinylated poly(dT) probe. At early stages of nuclear transformation, the distribution of small nuclear RNPs was similar to that previously described in non-infected nuclei (Visa, N., Puvion-Dutilleul, F., Bachellerie, J.P. and Puvion, E., Eur. J. Cell Biol. 60, 308–321, 1993; Visa, N., Puvion-Dutilleul, F., Harper, F., Bachellerie, J. P. and Puvion, E., Exp. Cell Res. 208, 19–34, 1993). As the infection progresses, the large virus-induced inclusion body consists of a central storage site of functionally inactive viral genomes surrounded by a peripheral shell formed by clusters of interchromatin granules, compact rings and a fibrillogranular network in which are embedded the viral single-stranded DNA accumulation sites. Spliceosome components and poly(A)+ RNAs were then exclusively detected over the clusters of interchromatin granules and the fibrillogranular network whereas the viral single-stranded DNA accumulation sites and compact rings remained unlabeled, thus appearing to not be directly involved in splicing. Our data, therefore, suggest that the fibrillogranular network, in addition to being the site of viral transcription, is also a major site of viral RNA splicing. Like the clusters of interchromatin granules, which had been already involved in spliceosome assembly, they could also have a role in the sorting of viral spliced polyadenylated mRNAs before export to the cytoplasm. The compact rings, which contain non-polyadenylated viral RNA, might accumulate the non-used portions of the viral transcripts resulting from differential poly(A)+ site selection.

scholarly journals Epitranscriptomic Dysregulation in Stress-induced Psychopathologies

2021 ◽  
Author(s):  
Dan Ohtan Wang ◽  
Kandarp Joshi ◽  
Anand Gururajan
Keyword(s):  
Rna Stability ◽  
Bioinformatic Analysis ◽  
Fine Tuning ◽  
Rna Modification ◽  
Mammalian Brain ◽  
Post Traumatic Stress ◽  
Specific Expression ◽  
Post Traumatic ◽  
Transcriptional Gene Regulation ◽  
Opening Up

AbstractTo date, over 100 different chemical modifications to RNA have been identified. Collectively known as the epitranscriptome, these modifications function to regulate RNA stability and as such, represent another mechanistic layer of post-transcriptional gene regulation. N6-methyladenosine (m6A) is the most common RNA modification in the mammalian brain and has been implicated in a number of processes relevant to neurodevelopment, brain function and behaviour. Here, following brief descriptions on epitranscriptomic mechanisms, we will review the literature on the potential functions of the m6A-methylome in fine-tuning gene expression which include prescribing localisation of transcripts in distal compartments as well as interactions with microRNAs and long non-coding RNAs. We will then discuss findings from rodent and human studies for stress-induced disorders - major depression and post-traumatic stress disorder – which support a hypothesis for a dysregulation of the m6A-methylome and the m6A-machinery in the pathophysiology. To support this, we have included a bioinformatic analysis of publicly available single-cell RNA-sequencing and bulk transcriptomics datasets which suggests an altered m6A-methylome as a consequence of dysregulated cell- and regionally-specific expression of key enzymes involved in the ‘writing, reading and erasing’ of m6A. We hope this review will generate further interest in the field of epitranscriptomics, opening up new lines of research into its involvement in psychiatric disorders.

S100A13 and S100A6 exhibit distinct translocation pathways in endothelial cells

2002 ◽  
Vol 115 (15) ◽  
pp. 3149-3158 ◽  
Author(s):  
Hsiao-Ling Hsieh ◽  
Beat W. Schäfer ◽  
Jos A. Cox ◽  
Claus W. Heizmann
Keyword(s):  
Endothelial Cells ◽  
Calcium Binding ◽  
Protein Translocation ◽  
S100 Proteins ◽  
Cellular Functions ◽  
Specific Expression ◽  
Binding Domains ◽  
Cellular Environment ◽  
Ef Hands ◽  
Physiological Tasks

S100 proteins have attracted great interest in recent years because of their cell- and tissue-specific expression and association with various human pathologies. Most S100 proteins are small acidic proteins with calcium-binding domains — the EF hands. It is thought that this group of proteins carry out their cellular functions by interacting with specific target proteins, an interaction that is mainly dependent on exposure of hydrophobic patches, which result from calcium binding. S100A13, one of the most recently identified members of the S100 family, is expressed in various tissues. Interestingly,hydrophobic exposure was not observed upon calcium binding to S100A13 even though the dimeric form displays two high- and two low- affinity sites for calcium. Here, we followed the translocation of S100A13 in response to an increase in intracellular calcium levels, as protein translocation has been implicated in assembly of signaling complexes and signaling cascades, and several other S100 proteins are involved in such events. Translocation of S100A13 was observed in endothelial cells in response to angiotensin II, and the process was dependent on the classic Golgi-ER pathway. By contrast, S100A6 translocation was found to be distinct and dependent on actin-stress fibers. These experiments suggest that different S100 proteins utilize distinct translocation pathways, which might lead them to certain subcellular compartments in order to perform their physiological tasks in the same cellular environment.

scholarly journals Evaluation of Viral RNA Recovery Methods in Vectors by Metagenomic Sequencing

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 562
Author(s):  
Joyce Odeke Akello ◽  
Stephen L. Leib ◽  
Olivier Engler ◽  
Christian Beuret
Keyword(s):  
Fold Increase ◽  
Extraction Methods ◽  
Viral Rna ◽  
Health Concern ◽  
Metagenomic Sequencing ◽  
Optimal Method ◽  
Viral Genomes ◽  
Tick Borne Encephalitis ◽  
Langat Virus ◽  
Tick Borne Encephalitis Virus

Identification and characterization of viral genomes in vectors including ticks and mosquitoes positive for pathogens of great public health concern using metagenomic next generation sequencing (mNGS) has challenges. One such challenge is the ability to efficiently recover viral RNA which is typically dependent on sample processing. We evaluated the quantitative effect of six different extraction methods in recovering viral RNA in vectors using negative tick homogenates spiked with serial dilutions of tick-borne encephalitis virus (TBEV) and surrogate Langat virus (LGTV). Evaluation was performed using qPCR and mNGS. Sensitivity and proof of concept of optimal method was tested using naturally positive TBEV tick homogenates and positive dengue, chikungunya, and Zika virus mosquito homogenates. The amount of observed viral genome copies, percentage of mapped reads, and genome coverage varied among different extractions methods. The developed Method 5 gave a 120.8-, 46-, 2.5-, 22.4-, and 9.9-fold increase in the number of viral reads mapping to the expected pathogen in comparison to Method 1, 2, 3, 4, and 6, respectively. Our developed Method 5 termed ROVIV (Recovery of Viruses in Vectors) greatly improved viral RNA recovery and identification in vectors using mNGS. Therefore, it may be a more sensitive method for use in arbovirus surveillance.

scholarly journals Site-specific methylation of the rat prolactin and growth hormone promoters correlates with gene expression.

1996 ◽  
Vol 16 (7) ◽  
pp. 3245-3254 ◽  
Author(s):  
V Ngô ◽  
D Gourdji ◽  
J N Laverrière
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Cell Lines ◽  
Anterior Pituitary ◽  
Regulatory Elements ◽  
Specific Expression ◽  
Site Specific ◽  
Cpg Dinucleotides ◽  
Cpg Sites

The methylation patterns of the rat prolactin (rPRL) (positions -440 to -20) and growth hormone (rGH) (positions -360 to -110) promoters were analyzed by bisulfite genomic sequencing. Two normal tissues, the anterior pituitary and the liver, and three rat pituitary GH3 cell lines that differ considerably in their abilities to express both genes were tested. High levels of rPRL gene expression were correlated with hypomethylation of the CpG dinucleotides located at positions -277 and -97, near or within positive cis-acting regulatory elements. For the nine CpG sites analyzed in the rGH promoter, an overall hypomethylation-expression coupling was also observed for the anterior pituitary, the liver, and two of the cell lines. The effect of DNA methylation was tested by measuring the transient expression of the chloramphenicol acetyltransferase reporter gene driven by a regionally methylated rPRL promoter. CpG methylation resulted in a decrease in the activity of the rPRL promoter which was proportional to the number of modified CpG sites. The extent of the inhibition was also found to be dependent on the position of methylated sites. Taken together, these data suggest that site-specific methylation may modulate the action of transcription factors that dictate the tissue-specific expression of the rPRL and rGH genes in vivo.

scholarly journals Stability of the Human Fragile X (CGG)n Triplet Repeat Array inSaccharomyces cerevisiae Deficient in Aspects of DNA Metabolism

1999 ◽  
Vol 19 (8) ◽  
pp. 5675-5684 ◽  
Author(s):  
Peter J. White ◽  
Rhona H. Borts ◽  
Mark C. Hirst
Keyword(s):  
Germ Line ◽  
Fragile X ◽  
Low Frequency ◽  
Triplet Repeat ◽  
Dependent Manner ◽  
Wild Type ◽  
Specific Expression ◽  
Repeat Array ◽  
Cellular Environment ◽  
Length Changes

ABSTRACT Expanded trinucleotide repeats underlie a growing number of human diseases. The human FMR1 (CGG) n array can exhibit genetic instability characterized by progressive expansion over several generations leading to gene silencing and the development of the fragile X syndrome. While expansion is dependent upon the length of uninterrupted (CGG) n , instability occurs in a limited germ line and early developmental window, suggesting that lineage-specific expression of other factors determines the cellular environment permissive for expansion. To identify these factors, we have established normal- and premutation-length human FMR1 (CGG) n arrays in the yeast Saccharomyces cerevisiae and assessed the frequency of length changes greater than 5 triplets in cells deficient in various DNA repair and replication functions. In contrast to previous studies withEscherichia coli, we observed a low frequency of orientation-dependent large expansions in arrays carrying long uninterrupted (CGG) n arrays in a wild-type background. This frequency was unaffected by deletion of several DNA mismatch repair genes or deletion of the EXO1 andDIN7 genes and was not enhanced through meiosis in a wild-type background. Array contraction occurred in an orientation-dependent manner in most mutant backgrounds, but loss of the Sgs1p resulted in a generalized increase in array stability in both orientations. In contrast, FMR1 arrays had a 10-fold-elevated frequency of expansion in a rad27 background, providing evidence for a role in lagging-strand Okazaki fragment processing in (CGG) n triplet repeat expansion.

scholarly journals Detection of the RNA for new multicomponent virus in patients with Crimean-Congo hemorrhagic fever in southern Russia

2020 ◽  
Author(s):  
Vladimir Ternovoi ◽  
Anastasia Gladysheva ◽  
Alexandra Sementsova ◽  
Anna Zaykovskaya ◽  
Anna Volynkina ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Hemorrhagic Fever ◽  
European Part ◽  
Viral Rna ◽  
Crimean Congo Hemorrhagic Fever ◽  
Viral Genomes ◽  
Cchf Virus ◽  
European Part Of Russia ◽  
Human Sera ◽  
Southern Russia

Background: Recently, a new multicomponent RNA-containing virus was described and called as Jingmen tick virus (JMTV) supposedly belonging to flaviviruses. A virus consists of four viral particles and JMTV was firstly isolated from ticks in China and South America. Aims: Detection viral RNA specific for JMTV complex, sequencing genome fragments and taxonomy identification novel virus from JMTV complex in patients with Crimean-Congo hemorrhagic fever (CCHF) from southern European part of Russia. Materials and methods: Panel of 20 randomly selected sera from patients with confirmed Crimean-Congo hemorrhagic fever was collected in 2016 and was used for detection JMTV and CCHF viral RNA by PCR with experimental primers. Subsequent sequencing of isolated fragments of viral genomes was used for identification JMTV and CCHF virus genetic materials and phylogenetic analyses. Results: The viral RNAs of the CCHF virus and JMTV were detected in blood of four patients. Sequencing of the isolated PCR fragment of S segment CCHF virus allowed identifying these RNA isolates as Europe 1 lineage, subgroups Va and Vb of the CCHF virus that is a typical for the southern European part of the Russia. The nucleotide sequences of segment 2 (GP glycoprotein) of the JMTV were also detected by RP PCR and sequencing in these human sera. The new JMTV isolates were clustered together by phylogenetic analysis. The level of nucleotide identity for newly discovered JMTV isolates was only about 81-82% with comparison to the previously described European variants (Kosovo) of the JMTV. Conclusions: The results suggest that viral genomic RNA for new multicomponent flavivirus named as Manych virus and related to the JMTV complex was discovered in sera of CCHF patients in Russia.

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