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Context: Recently, a few antiviral drugs viz Molnupiravir (EIDD-1931), Favipiravir, Ribavirin, Sofosbuvir, Galidesivir, and Remdesivir are shown to be beneficial against COVID-19 disease. These drugs bind to the viral RNA single strand to inhibit the virus genome replication. Similarly, recently, some artificial nucleotides, such as P, J, B, X, Z, V, S, and K were proposed to behave as potent antiviral candidates. However, their activity in the presence of the most reactive hydroxyl (OH) radical is not yet known. Here, the possibility of RNA strand break due to the OH radical-induced C1′-hydrogen (H) abstraction reaction of the above molecules (except Remdesivir) is studied in detail by considering their nucleotide conformation. The results are compared with those of the natural RNA nucleotides (G, C, A, and U). Due to low Gibbs barrier-free energy and high exothermicity, all these nucleotides (except Remdesivir) are prone to OH radical-induced C1′-H abstraction reaction. As Remdesivir contains a C1′-CN bond, the OH radical substitution reactions at the CN and C1′ sites would likely liberate the catalytically important CN group, thereby downgrading its activity. Method: Initially, the B3LYP-D3 dispersion-corrected density functional theory method and 6–31 + G* basis set were used to optimize all reactant, transition state, and product complexes in the implicit aqueous medium. Subsequently, the structures of these complexes were further optimized by using the ωB97X-D dispersion-corrected density functional theory method and cc-PVTZ basis set in the aqueous medium. The IEFPCM method was used to model the aqueous medium. [ABSTRACT FROM AUTHOR]

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology. Within this work, we integrate a two-year genotyping window with structural biology to explore the selective pressures of SARS-CoV-2 on protein insights. Although genotype and the Spike (Surface Glycoprotein) protein continue to drift, most SARS-CoV-2 proteins have had few amino acid alterations. Within Spike, the high drift rate of amino acids involved in antibody evasion also corresponds to changes within the ACE2 binding pocket that have undergone multiple changes that maintain functional binding. The genotyping suggests selective pressure for receptor specificity that could also confer changes in viral risk. Mapping of amino acid changes to the structures of the SARS-CoV-2 co-transcriptional complex (nsp7-nsp14), nsp3 (papain-like protease), and nsp5 (cysteine protease) proteins suggest they remain critical factors for drug development that will be sustainable, unlike those strategies targeting Spike. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is caused by a novel and rapidly mutating coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although several drugs are already in clinical use or under emergency authorization, there is still an urgent need to develop new drugs. Through the mining and analysis of 2776 genomes of the SARS-CoV-2 virus, we identified papain-like protease (PLpro), which is a critical enzyme required for coronavirus to generate a functional replicase complex and manipulate post-translational modifications on host proteins for evasion against host antiviral immune responses, as a conserved molecular target for the development of anti-SARS-CoV-2 therapy. We then made an infection model using the NCI-H1299 cell line stably expressing SARS-CoV-2 PLpro protein (NCI-H1299/PLpro). To investigate the effect of targeting and degrading PLpro mRNA, a compact CRISPR-Cas13 system targeting PLpro mRNA was developed and validated, which was then delivered to the aforementioned NCI-H1299/PLpro cells. The results showed that CRISPR-Cas13 mediated mRNA degradation successfully reduced the expression of viral PLpro protein. By combining the power of AAV and CRISPR-Cas13 technologies, we aim to explore the potential of attenuating viral infection by targeted degradation of important viral mRNAs via safe and efficient delivery of AAV carrying the CRISPR-Cas13 system. This study demonstrated a virus-against-virus gene therapy strategy for COVID-19 and provided evidence for the future development of therapies against SARS-CoV-2 and other RNA viral infections. [ABSTRACT FROM AUTHOR]

A comprehensive and systematic examination of dengue virus (DENV) evolution is essential in Pakistan, where the virus poses a significant public health challenge due to its ability to adapt and evolve. To shed light on the intricate evolutionary patterns of all four DENV serotypes, we analyzed complete genome sequences (n = 43) and Envelope (E) gene sequences (n = 44) of all four DENV serotypes collected in Pakistan from 1994 to 2023, providing a holistic view of their genetic evolution. Our findings revealed that all four serotypes of DENV co-circulate in Pakistan with a close evolutionary relationship between DENV-1 and DENV-3. Among the genetically distinct serotypes DENV-2 and DENV-4, DENV-4 stands out as the most genetically different, while DENV-2 exhibits greater complexity due to the presence of multiple genotypes and the possibility of temporal fluctuations in genotype prevalence. Selective pressure analysis of the Envelope (E) gene revealed heterogeneity among sequences (n = 44), highlighting 46 codons in the genome experiencing selective pressure, characterized by a bias toward balancing selection, indicating genetic stability of the virus. Furthermore, our study suggested an intriguing evolutionary shift of DENV-4 toward the DENV-2 clade, potentially influenced by antibodies with cross-reactivity to multiple serotypes, providing a critical insight into the complex factors, shaping DENV evolution and contributing to the emergence of new serotypes. [ABSTRACT FROM AUTHOR]

Enteroviruses are RNA viruses that initiate infections through the gastrointestinal (GI) tract and are associated with enteric illness in individuals of all ages. Most serious infections of enteroviruses are in infants and young children where it is the common cause of aseptic meningitis and other systemic diseases, leading to a high mortality rate. Enteroviruses belong to the small non-enveloped family of the Picornaviridae family. The virus can spread mainly through fecal–oral and respiratory routes. In the Arabian Gulf countries, the incidence of enteroviral infections is only restricted to a few reports, and thus, knowledge of the epidemiology, characteristics, and pathogenesis of the virus in the gulf countries remains scarce. In this minireview, we sought to provide an overview of the characteristics of enterovirus and its pathogenesis, in addition to gathering the reports of enterovirus infection prevalence in Gulf Cooperation Council (GCC) countries. We also present a summary of the common methods used in its detection. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is caused by a novel and rapidly mutating coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although several drugs are already in clinical use or under emergency authorization, there is still an urgent need to develop new drugs. Through the mining and analysis of 2776 genomes of the SARS-CoV-2 virus, we identified papain-like protease (PLpro), which is a critical enzyme required for coronavirus to generate a functional replicase complex and manipulate post-translational modifications on host proteins for evasion against host antiviral immune responses, as a conserved molecular target for the development of anti-SARS-CoV-2 therapy. We then made an infection model using the NCI-H1299 cell line stably expressing SARS-CoV-2 PLpro protein (NCI-H1299/PLpro). To investigate the effect of targeting and degrading PLpro mRNA, a compact CRISPR-Cas13 system targeting PLpro mRNA was developed and validated, which was then delivered to the aforementioned NCI-H1299/PLpro cells. The results showed that CRISPR-Cas13 mediated mRNA degradation successfully reduced the expression of viral PLpro protein. By combining the power of AAV and CRISPR-Cas13 technologies, we aim to explore the potential of attenuating viral infection by targeted degradation of important viral mRNAs via safe and efficient delivery of AAV carrying the CRISPR-Cas13 system. This study demonstrated a virus-against-virus gene therapy strategy for COVID-19 and provided evidence for the future development of therapies against SARS-CoV-2 and other RNA viral infections.

Abstract HIV-1 drug resistance genotypic tests have primarily been performed by Sanger sequencing of gene segments encoding different drug target proteins. Since the number of targets has increased with the addition of a new class of antiretroviral drugs, a simple high-throughput system for assessing nucleotide sequences throughout the HIV-1 genome is required. Here, we developed a new solution using nanopore sequencing of viral pangenomes amplified by PCR. Benchmark tests using HIV-1 molecular clones demonstrated an accuracy of up to 99.9%. In addition, validation tests of our protocol in 106 clinical samples demonstrated high concordance of drug resistance and tropism genotypes (92.5% and 98.1%, respectively) between the nanopore sequencing-based results and archived clinical determinations made based on Sanger sequencing data. These results suggest that our new approach will be a powerful solution for the comprehensive survey of HIV-1 drug resistance mutations in clinical settings.

This article summarizes a study that investigated the presence and viability of the SARS-CoV-2 virus in breast milk samples from postpartum women. The study found that the virus's genetic material could be detected in breast milk, but there was no evidence of the virus being able to replicate. These findings support the recommendation to continue breastfeeding even if the mother has a SARS-CoV-2 infection. However, more research is needed to understand the impact of vaccination on the presence and viability of the virus in breast milk. The study was approved by the Research Ethics Committee of the University of Campinas. [Extracted from the article]

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most globally devastating viruses threatening the swine industry worldwide. Substantial advancements have been achieved in recent years towards comprehending the pathogenesis of PRRSV infection and the host response, involving both innate and adaptive immune responses. Not only a multitude of host proteins actively participate in intricate interactions with viral proteins, but microRNAs (miRNAs) also play a pivotal role in the host response to PRRSV infection. If a PRRSV--host interaction at the protein level is conceptualized as the front line of the battle between pathogens and host cells, then their fight at the RNA level resembles the hidden front line. miRNAs are endogenous small non-coding RNAs of approximately 20--25 nucleotides (nt) that primarily regulate the degradation or translation inhibition of target genes by binding to the 3'-untranslated regions (UTRs). Insights into the roles played by viral proteins and miRNAs in the host response can enhance our comprehensive understanding of the pathogenesis of PRRSV infection. The intricate interplay between viral proteins and cellular targets during PRRSV infection has been extensively explored. This review predominantly centers on the contemporary understanding of the host response to PRRSV infection at the RNA level, in particular, focusing on the twenty-six miRNAs that affect viral replication and the innate immune response. [ABSTRACT FROM AUTHOR]

The tick-borne encephalitis virus (TBEV) strain C11-13 (GenBank acc. no. OQ565596) of the Siberian genotype was previously isolated from the brain of a deceased person. TBEV C11-13 variants obtained at passages 3 and 8 in SPEV cells were inoculated into the brains of white mice for subsequent passages. Full genome sequences of all virus variants were analyzed by high-throughput sequencing. A total of 41 single nucleotide substitutions were found to occur mainly in the genes for the nonstructural proteins NS3 and NS5 (GenBank MF043953, OP902894, and OP902895), and 12 amino acid substitutions were identified in the deduced protein sequences. Reverse nucleotide and amino acid substitutions were detected after three passages through mouse brains. The substitutions restored the primary structures that were characteristic of the isolate C11-13 from a human patient and changed during the eight subsequent passages in SPEV cells. In addition, the 3′-untranslated region (3′-UTR) of the viral genome increased by 306 nt. The Y3 and Y2 3'-UTR elements were found to contain imperfect L and R repeats, which were probably associated with inhibition of cellular XRN1 RNase and thus involved in the formation of subgenomic flaviviral RNAs (sfRNAs). All TBEV variants showed high-level reproduction in both cell cultures and mouse brains. The genomic changes that occurred during successive passages of TBEV are most likely due to its significant genetic variability, which ensures its efficient reproduction in various hosts and its broad distribution in various climatic zones. [ABSTRACT FROM AUTHOR]

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology. Within this work, we integrate a two-year genotyping window with structural biology to explore the selective pressures of SARS-CoV-2 on protein insights. Although genotype and the Spike (Surface Glycoprotein) protein continue to drift, most SARS-CoV-2 proteins have had few amino acid alterations. Within Spike, the high drift rate of amino acids involved in antibody evasion also corresponds to changes within the ACE2 binding pocket that have undergone multiple changes that maintain functional binding. The genotyping suggests selective pressure for receptor specificity that could also confer changes in viral risk. Mapping of amino acid changes to the structures of the SARS-CoV-2 co-transcriptional complex (nsp7-nsp14), nsp3 (papain-like protease), and nsp5 (cysteine protease) proteins suggest they remain critical factors for drug development that will be sustainable, unlike those strategies targeting Spike.

Marek's disease (MD) is a highly infectious lymphoproliferative disease in chickens with a significant economic impact. Mardivirus gallidalpha 2, also known as Marek's disease virus (MDV), is the causative pathogen and has been categorized based on its virulence rank into four pathotypes: mild (m), virulent (v), very virulent (vv), and very virulent plus (vv+). A prior comparative genomics study suggested that several single-nucleotide polymorphisms (SNPs) and genes in the MDV genome are associated with virulence, including nonsynonymous (ns) SNPs in eight open reading frames (ORF): UL22, UL36, UL37, UL41, UL43, R-LORF8, R-LORF7, and ICP4. To validate the contribution of these nsSNPs to virulence, the vv+MDV strain 686 genome was modified by replacing nucleotides with those observed in the vMDV strains. Pathogenicity studies indicated that these substitutions reduced the MD incidence and increased the survival of challenged birds. Furthermore, using the best-fit pathotyping method to rank the virulence, the modified vv+MDV 686 viruses resulted in a pathotype similar to the vvMDV Md5 strain. Thus, these results support our hypothesis that SNPs in one or more of these ORFs are associated with virulence but, as a group, are not sufficient to result in a vMDV pathotype, suggesting that there are additional variants in the MDV genome associated with virulence, which is not surprising given this complex phenotype and our previous finding of additional variants and SNPs associated with virulence. [ABSTRACT FROM AUTHOR]

Enteroviruses are RNA viruses that initiate infections through the gastrointestinal (GI) tract and are associated with enteric illness in individuals of all ages. Most serious infections of enteroviruses are in infants and young children where it is the common cause of aseptic meningitis and other systemic diseases, leading to a high mortality rate. Enteroviruses belong to the small non-enveloped family of the Picornaviridae family. The virus can spread mainly through fecal–oral and respiratory routes. In the Arabian Gulf countries, the incidence of enteroviral infections is only restricted to a few reports, and thus, knowledge of the epidemiology, characteristics, and pathogenesis of the virus in the gulf countries remains scarce. In this minireview, we sought to provide an overview of the characteristics of enterovirus and its pathogenesis, in addition to gathering the reports of enterovirus infection prevalence in Gulf Cooperation Council (GCC) countries. We also present a summary of the common methods used in its detection.

ABSTRACT The monkeypox virus (MPX) belongs to the Orthopoxvirus genus of the Poxviridae family, is endemic in parts of Africa and causes a disease in humans similar to smallpox. The most recent outbreak of MPX is already affecting 110 countries, with 86,956 confirmed cases since May 2022 and has consequently become a focus of interest. In particular, a molecular understanding of the virus is essential to study infection processes and pathogen-host interactions, predict tropism changes, or guide drug development and drug discovery as well as vaccine development or vaccine adaptation at a very early stage. Herein, we present a study of the structural proteome of the currently circulating MPX: Our consensus analysis of 3,713 genome sequences sampled within a year after the outbreak revealed 10,580 characteristic candidate open reading frames (ORFs). A search in the non-redundant protein database reduced the number of suspected ORFs to 1,079, of which 210 are representative proteins in typical MPX reference genomes. This should serve as a collection of putative proteins within the currently spreading MPX, a compound of information that could support timely drug discovery, mutational analyses, and vaccine development. We, herein, present the so far most comprehensive structural proteome by providing atomistic 3D models of 210 proteins, generated with three state-of-the-art structure prediction methods, including a mutational analysis of the proteome, with a particular focus on the drug-binding sites of tecovirimat and brincidofovir. IMPORTANCE The 2022 outbreak of the monkeypox virus already involves, by April 2023, 110 countries with 86,956 confirmed cases and 119 deaths. Understanding an emerging disease on a molecular level is essential to study infection processes and eventually guide drug discovery at an early stage. To support this, we provide the so far most comprehensive structural proteome of the monkeypox virus, which includes 210 structural models, each computed with three state-of-the-art structure prediction methods. Instead of building on a single-genome sequence, we generated our models from a consensus of 3,713 high-quality genome sequences sampled from patients within 1 year of the outbreak. Therefore, we present an average structural proteome of the currently isolated viruses, including mutational analyses with a special focus on drug-binding sites. Continuing dynamic mutation monitoring within the structural proteome presented here is essential to timely predict possible physiological changes in the evolving virus.

Numerous genomic analyses of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have been conducted, highlighting its variations and lineage transitions. Despite the importance of forensic autopsy in investigating deaths due to coronavirus disease 2019 (COVID‐19), including out‐of‐hospital deaths, viral genomic analysis has rarely been reported due in part to postmortem changes. In this study, various specimens were collected from 18 forensic autopsy cases with SARS‐CoV‐2 infection. Reverse‐transcription quantitative polymerase chain reaction revealed the distribution of the virus in the body, primarily in the respiratory organs. Next‐generation sequencing determined the complete genome sequences in 15 of the 18 cases, although some cases showed severe postmortem changes or degradation of tissue RNA. Intrahost genomic diversity of the virus was identified in one case of death due to COVID‐19. The accumulation of single‐nucleotide variations in the lung of the case suggested the intrahost evolution of SARS‐CoV‐2. Lung of the case showed diffuse alveolar damage histologically and positivity for SARS‐CoV‐2 by immunohistochemical analysis and in situ hybridization, indicating virus‐associated pneumonia. This study provides insights into the feasibility of genomic analysis of SARS‐CoV‐2 in forensic autopsy cases and the potential for uncovering important information in COVID‐19 deaths, including out‐of‐hospital deaths. [ABSTRACT FROM AUTHOR]

Viruses are ubiquitous microbiome components, shaping ecosystems via strain-specific predation, horizontal gene transfer and redistribution of nutrients through host lysis. Viral impacts are important in groundwater ecosystems, where microbes drive many nutrient fluxes and metabolic processes; however, little is known about the diversity of viruses in these environments. We analyzed four groundwater plasmidomes (the entire plasmid content of an environment) and identified 200 viral sequences, which clustered into 41 genus-level viral clusters (approximately equivalent to viral genera) including 9 known and 32 putative new genera. We used publicly available bacterial whole-genome sequences (WGS) and WGS from 261 bacterial isolates from this groundwater environment to identify potential viral hosts. We linked 76 of the 200 viral sequences to a range of bacterial phyla, the majority associated with Proteobacteria, followed by Firmicutes, Bacteroidetes, and Actinobacteria. The publicly available WGS enabled mapping bacterial hosts to several viral sequences. The WGS of groundwater isolates increased the depth of host prediction by allowing host identification at the strain level. The latter included 4 viruses that were almost entirely (>99% query coverage, >99% identity) identified as integrated in the genomes of Pseudomonas, Acidovorax, and Castellaniella strains, resulting in high-confidence host assignments. Lastly, 21 of these viruses carried putative auxiliary metabolite genes for metal and antibiotic resistance, which might drive their infection cycles and/or provide selective advantage to infected hosts. Exploring the groundwater virome provides a necessary foundation for integration of viruses into ecosystem models where they are key players in microbial adaption to environmental stress. IMPORTANCE To our knowledge, this is the first study to identify the bacteriophage distribution in a groundwater ecosystem shedding light on their prevalence and distribution across metal-contaminated and background sites. Our study is uniquely based on selective sequencing of solely the extrachromosomal elements of a microbiome followed by analysis for viral signatures, thus establishing a more focused approach for phage identifications. Using this method, we detected several novel phage genera along with those previously established. Our approach of using the whole-genome sequences of hundreds of bacterial isolates from the same site enabled us to make host assignments with high confidence, several at strain levels. Certain phage genes suggest that they provide an environment-specific selective advantage to their bacterial hosts. Our study lays the foundation for future research on directed phage isolations using specific bacterial host strains to further characterize groundwater phages, their life cycles, and their effects on groundwater microbiome and biogeochemistry.

• A COVID-19 outbreak occurred in a nursing home that did not provide medical care. • Most of the residents with severe hypoxemia could not be transferred to a hospital. • Despite vaccination, high mortality and morbidity were observed among the residents. • All genomes from residents and staff belonged to the Omicron variant BA.1. • Avoiding management of severe COVID-19 cases in nursing homes is needed. Outbreaks of coronavirus disease 2019 (COVID-19) in long-term care facilities are associated with mortality, although vaccination have contributed to improvements. This study reports clinical impacts of a COVID-19 outbreak in a nursing home for elderly individuals in Kyoto City, Japan. We performed epidemiologic and molecular investigations of the outbreak and characterized outcomes of the nursing home residents. During the outbreak period, a total of 31 residents (39.2%) and 26 staff members (49.1%) were infected with COVID-19. All residents and staff received two doses of a vaccine approximately 7 months prior. Ten residents with severe hypoxemia could not be transferred to a hospital due to a shortage of beds for COVID-19 patients. Within 90 days of the onset of the outbreak, 8 residents with COVID-19 (25.8%) died. A total of 48.4% of residents with COVID-19 developed 1 or more comorbidities. Viral genome analysis showed that the outbreak was caused by the Omicron BA.1.1.2 variant. Despite vaccination, high mortality and morbidity were observed in the COVID-19 outbreak due to the Omicron variant. Limiting medical care for residents with COVID-19 in facilities that experience ongoing outbreaks may be needed to reduce the risk of mortality among nursing home residents. [ABSTRACT FROM AUTHOR]

Abstract Background Genomics and virology are unquestionably important, but complex, domains being investigated by a large number of scientists. The need to facilitate and support work within these domains requires sharing of databases, although it is often difficult to do so because of the different ways in which data is represented across the databases. To foster semantic interoperability, models are needed that provide a deep understanding and interpretation of the concepts in a domain, so that the data can be consistently interpreted among researchers. Results In this research, we propose the use of conceptual models to support semantic interoperability among databases and assess their ontological clarity to support their effective use. This modeling effort is illustrated by its application to the Viral Conceptual Model (VCM) that captures and represents the sequencing of viruses, inspired by the need to understand the genomic aspects of the virus responsible for COVID-19. For achieving semantic clarity on the VCM, we leverage the “ontological unpacking” method, a process of ontological analysis that reveals the ontological foundation of the information that is represented in a conceptual model. This is accomplished by applying the stereotypes of the OntoUML ontology-driven conceptual modeling language.As a result, we propose a new OntoVCM, an ontologically grounded model, based on the initial VCM, but with guaranteed interoperability among the data sources that employ it. Conclusions We propose and illustrate how the unpacking of the Viral Conceptual Model resolves several issues related to semantic interoperability, the importance of which is recognized by the “I” in FAIR principles. The research addresses conceptual uncertainty within the domain of SARS-CoV-2 data and knowledge.The method employed provides the basis for further analyses of complex models currently used in life science applications, but lacking ontological grounding, subsequently hindering the interoperability needed for scientists to progress their research.

Background: With the rapid development of the genomic sequence data for the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants Delta (B.1.617.2) and Omicron (B.1.1.529), it is vital to successfully identify mutations within the genome. Objective: The main objective of the study is to investigate the full-length genome mutation analysis of 157 SARS-CoV-2 and its variant Delta and Omicron isolates. This study also provides possible effects at the structural level to understand the role of mutations and new insights into the evolution of COVID-19 and evaluates the differential level analysis in viral genome sequence among different nations. We have also tried to offer a mutation snapshot for these differences that could help in vaccine formulation. This study utilizes a unique and efficient method of targeting the stable genes for the drug discovery approach. Methods: Complete genome sequence information of SARS-CoV-2, Delta, and Omicron from online resources were used to predict structure domain identification, data mining, and screening; employing different bioinformatics tools. BioEdit software was used to perform their genomic alignments across countries and a phylogenetic tree as per the confidence of 500 bootstrapping values was constructed. Heterozygosity ratios were determined in-silico. A minimum spanning network (MSN) of selected populations was determined by Bruvo's distance role-based framework. Results: Out of all 157 different strains of SARS-CoV-2 and its variants, and their complete genome sequences from different countries, Corona nucleoca and DUF5515 were observed to be the most conserved domains. All genomes obtained changes in comparison to the Wuhan-Hu-1 strain, mainly in the TRS region (CUAAAC or ACGAAC). We discovered 596 mutations in all genes, with the highest number (321) found in ORF1ab (QHD43415.1), or TRS site mutations found only in ORF7a (1) and ORF10 (2). The Omicron variant has 30 mutations in the Spike protein and has a higher alpha-helix shape (23.46%) than the Delta version (22.03%). T478 was also discovered to be a prevalent polymorphism in Delta and Omicron variations, as well as genomic gaps ranging from 45 to 65aa. All 157 sequences contained variations and conformed to Nei's Genetic distance. We discovered heterozygosity (Hs) 0.01, mean anticipated Hs 0.32, the genetic diversity index (GDI) 0.01943989, and GD within population 0.01266951. The Hedrick value was 0.52324978, the GD coefficient was 0.52324978, the average Hs was 0.01371452, and the GD coefficient was 0.52324978. Among other countries, Brazil has the highest standard error (SE) rate (1.398), whereas Japan has the highest ratio of Nei's gene diversity (0.01). Conclusions: The study's findings will assist in comprehending the shape and kind of complete genome, their streaming genomic sequences, and mutations in various additions of SARS-CoV-2, as well as its different variant strains like Omicron. These results will provide a scientific basis to design the vaccines and understand the genomic study of these viruses.

Influenza virus contains a single-stranded negative-sense RNA genome. Replication of the genome is carried out by the viral RNA-dependent RNA polymerase in the context of the viral ribonucleoprotein (RNP) complex, through a positive-sense complementary RNA intermediate. Genome replication is tightly controlled through interactions with accessory viral and host factors. Propelled by developments in recombinant protein expression, and technical improvements in X-ray crystallography and cryo-electron microscopy, snapshots of the replication process have been captured. Here, we review how recent structural data shed light on the molecular mechanisms of influenza virus genome replication, in particular, encapsidation of nascent RNA, de novo RNP assembly, and regulation of replication initiation through interactions with host and viral cues. Influenza virus RNA genome replication is carried out by a dimeric form of the influenza virus RNA polymerase with one of the polymerases acting as a replicating polymerase, synthesizing product RNA, and the other acting as an encapsidating polymerase, capturing the nascent RNA product and initiating its assembly into a ribonucleoprotein (RNP) complex. Proteins of the acidic nuclear phosphoprotein 32 (ANP32) family, essential host factors for influenza virus RNA genome replication, bridge the replicating and encapsidating polymerase. The disordered highly acidic C-terminal tail of ANP32 proteins acts as a platform for binding viral nucleoprotein, increasing nucleoprotein density around the site of RNA genome replication, and thus facilitating its recruitment to nascent viral RNA. Using a dimeric form of the viral RNA polymerase to replicate viral genomic RNA could be a general feature of negative-sense RNA viruses. [ABSTRACT FROM AUTHOR]

Marek’s disease (MD) is a highly infectious lymphoproliferative disease in chickens with a significant economic impact. Mardivirus gallidalpha 2, also known as Marek’s disease virus (MDV), is the causative pathogen and has been categorized based on its virulence rank into four pathotypes: mild (m), virulent (v), very virulent (vv), and very virulent plus (vv+). A prior comparative genomics study suggested that several single-nucleotide polymorphisms (SNPs) and genes in the MDV genome are associated with virulence, including nonsynonymous (ns) SNPs in eight open reading frames (ORF): UL22, UL36, UL37, UL41, UL43, R-LORF8, R-LORF7, and ICP4. To validate the contribution of these nsSNPs to virulence, the vv+MDV strain 686 genome was modified by replacing nucleotides with those observed in the vMDV strains. Pathogenicity studies indicated that these substitutions reduced the MD incidence and increased the survival of challenged birds. Furthermore, using the best-fit pathotyping method to rank the virulence, the modified vv+MDV 686 viruses resulted in a pathotype similar to the vvMDV Md5 strain. Thus, these results support our hypothesis that SNPs in one or more of these ORFs are associated with virulence but, as a group, are not sufficient to result in a vMDV pathotype, suggesting that there are additional variants in the MDV genome associated with virulence, which is not surprising given this complex phenotype and our previous finding of additional variants and SNPs associated with virulence.

With over 5.5 million deaths worldwide attributed to the respiratory disease COVID-19 caused by the novel coronavirus SARS-CoV-2, it is essential that continued efforts be made to track the evolution and spread of the virus globally. The authors previously presented a rapid and cost-effective method to sequence the entire SARS-CoV-2 genome with 95% coverage and 99.9% accuracy. This method is advantageous for identifying and tracking variants in the SARS-CoV-2 genome compared with traditional short-read sequencing methods which can be time-consuming and costly. Herein, the addition of genotyping probes to a DNA chip that targets known SARS-CoV-2 variants is presented. The incorporation of genotyping probe sets along with the advent of a moving average filter improved the sequencing coverage and accuracy of the SARS-CoV-2 genome. Throughout the COVID-19 pandemic the virus known as SARS-CoV-2 has continued to mutate and evolve. It is imperative to continue to track these mutations and where the virus has traveled to best inform healthcare practices and global strategies to combat the virus. The authors previously developed a method to investigate 95% of this viral genome with 99.9% accuracy that was more cost-effective and less time-consuming than previous methods. In this work, specific markers were added to the technology to allow tracking of mutations in the virus that have already been documented. In doing so, the accuracy and how much of the viral genome can be sequenced was improved. SARS-CoV-2 genome tiling array helping to combat the #COVID-19 pandemic by tracking viral evolution in a rapid and cost-effective manner with 99.59% genome coverage and 99.98% accuracy. [ABSTRACT FROM AUTHOR]

High-throughput RNA sequencing (RNA-seq) analysis of samples from Mallotus japonicus, a traditional medicinal plant, yielded two novel RNA viruses tentatively named Mallotus japonicus virus A (MjVA) and Mallotus japonicus virus B (MjVB). The MjVA and MjVB genomes encode proteins showing amino acid sequence similarities to those of poleroviruses (the genus Polerovirus, the family Solemoviridae) and amalgaviruses (the genus Amalgavirus, the family Amalgaviridae), respectively. The MjVA genome con- tains seven highly overlapping open reading frames, which are translated to seven proteins through various translational mechanisms, including -1 programmed ribosomal frameshifting (PRF) at the slippery motif GGGAAAC, non-AUG translational initiation, and stop codon readthrough. The MjVB genome encodes two proteins; one of which is translated by +1 PRF mechanism at the slippery motif UUUCGN. The abundance analysis of virus-derived RNA fragments revealed that MjVA is highly concentrated in plant parts with well-developed phloem tissues as previously demonstrated in other poleroviruses, which are transmitted by phloem feeders, such as aphids. MjVB, an amalgavirus generally transmitted by seeds, is distributed in all samples at low concentrations. Thus, this study demonstrates the effectiveness and usefulness of RNA-seq analysis of plant samples for the identification of novel RNA viruses and analysis of their tissue distribution. [ABSTRACT FROM AUTHOR]

Background: Genomics and virology are unquestionably important, but complex, domains being investigated by a large number of scientists. The need to facilitate and support work within these domains requires sharing of databases, although it is often difficult to do so because of the different ways in which data is represented across the databases. To foster semantic interoperability, models are needed that provide a deep understanding and interpretation of the concepts in a domain, so that the data can be consistently interpreted among researchers. Results: In this research, we propose the use of conceptual models to support semantic interoperability among databases and assess their ontological clarity to support their effective use. This modeling effort is illustrated by its application to the Viral Conceptual Model (VCM) that captures and represents the sequencing of viruses, inspired by the need to understand the genomic aspects of the virus responsible for COVID-19. For achieving semantic clarity on the VCM, we leverage the "ontological unpacking" method, a process of ontological analysis that reveals the ontological foundation of the information that is represented in a conceptual model. This is accomplished by applying the stereotypes of the OntoUML ontology-driven conceptual modeling language.As a result, we propose a new OntoVCM, an ontologically grounded model, based on the initial VCM, but with guaranteed interoperability among the data sources that employ it. Conclusions: We propose and illustrate how the unpacking of the Viral Conceptual Model resolves several issues related to semantic interoperability, the importance of which is recognized by the "I" in FAIR principles. The research addresses conceptual uncertainty within the domain of SARS-CoV-2 data and knowledge.The method employed provides the basis for further analyses of complex models currently used in life science applications, but lacking ontological grounding, subsequently hindering the interoperability needed for scientists to progress their research. [ABSTRACT FROM AUTHOR]

Abstract Background Dengue virus (DENV) is a member of insect vector-borne viruses, and it causes dengue fever. Southeast Asia is the epi-center of dengue fever in the world. The characterization of the virus is essential to identify the transmission and evolution of DENV. Objectives In 2017, there was an outbreak of Dengue virus type 1 (DENV1) in northern Vietnam and the neighboring countries. To identify the genetic character of the outbreak virus in the area, we conducted whole-genome sequencing analysis on the samples positive for the DENV1 along with real-time PCR. Study design In total, 1026 blood samples were collected from patients with suspected dengue fever in Ha Nam and Hai Duong province, nearby areas of the capital of Vietnam. After screening by real-time PCR, 40 of DENV1 positive samples were subjected to whole-genome sequencing, and 28 complete coding sequences were obtained. Results All 28 sequences were genotype I of DENV1, which is dominant in the southeast and East Asian countries. The phylogenetic analysis of the E region showed that they fell into a single cluster with the reported sequences from Vietnam between 2009 and 2016, in which the isolates from other countries are very rare. Our results suggested that the 2017 outbreak in the area was caused by locally circulating viruses.

Respiratory viruses infection is a worldwide human concern annually. The main viral respiratory diseases are caused by a variety of viruses sharing similar threats and affecting the respiratory system. Among all, influenza viruses, respiratory syncytial virus, parainfluenza viruses, respiratory adenoviruses, rhinoviruses, human bocaviruses, human metapneumovirus and coronaviruses are the main common respiratory viruses affecting human population. The recent coronavirus disease 19 pandemic has revealed critical knowledge gaps required to update in the transmission and pathological induced pathways for respiratory viruses. To date, several evidences suggest that human viruses can hijack extracellular vesicles (EVs) to deliver proteins, mRNAs, microRNAs and whole viral particles during viral life cycle in the host. Thus, several investigations have reported that also respiratory viruses use EVs to deliver viral nucleic acid and proteins, even including the potentiality of carrying whole viral particle. This evidence demonstrates the ability of the EVs produced in infected cells to deliver respiratory viral components to uninfected cells, positively or negatively counteracting new viral infection. Additionally, EVs derived from biological fluids of clinical samples may increase the risk to induce severe respiratory viruses-associated diseases in site far from the respiratory tract and for prolonged time. Here, it has been reviewed the advantages of the respiratory viruses EVs interaction regarding their ability to enhance viral infection, to evade antiviral response, to regulate virus-immune response and to mediate diseases. All these data confirm a potential role of the association between EVs and respiratory viruses infection. This suggests that further studies to define the implication of this interaction in viral life cycle in human population are needed.

Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bats are reservoirs for diverse coronaviruses, including swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV was first identified in diarrheal piglets in 2017. As a novel alphacoronavirus, SADS-CoV shares ;95% identity with bat alphacoronavirus HKU2. SADS-CoV has been reported to have broad cell tropism and inherent potential to cross host species barriers for dissemination. Thus far, no effective antiviral drugs or vaccines are available to treat infections with SADS-CoV. Therefore, knowledge of the protein-coding gene set and a subcellular localization map of SADS-CoV proteins are fundamental first steps in this endeavor. Here, all SADS-CoV genes were cloned separately into Flag-tagged plasmids, and the subcellular localizations of viral proteins, with the exception of nsp11, were detected using confocal microscopy techniques. As a result, nsp1, nsp3-N, nsp4, nsp5, nsp7, nsp8, nsp9, nsp10, nsp14, and nsp15 were localized in the cytoplasm and nuclear spaces, and these viral proteins may perform specific functions in the nucleus. All structural and accessory proteins were mainly localized in the cytoplasm. NS7a and membrane protein M colocalized with the Golgi compartment, and they may regulate the assembly of SADS-CoV virions. Maturation of SADS-CoV may occur in the late endosomes, during which envelope protein E is involved in the assembly and release of the virus. In summary, the present study demonstrates for the first time the location of all the viral proteins of SADS-CoV. These fundamental studies of SADS-CoV will promote studies of basic virology of SADS-CoV and support preventive strategies for animals with infection of SADS-CoV. [ABSTRACT FROM AUTHOR]

Afin de comprendre le syndrome d'immunodéficience humaine acquise et son traitement, il est important de connaître la structure des virus de l'immunodéficience humaine et leurs mécanismes de réplication dans les cellules infectées, particulièrement les phases cibles des antirétroviraux. La notion de variabilité, qui permet à ces virus d'échapper à l'immunité et aux thérapeutiques antirétrovirales, est tout aussi capitale. In order to understand acquired human immunodeficiency syndrome and its treatment, it is important to know the structure of human immunodeficiency viruses and their replication mechanisms in infected cells, particularly the target phases of antiretroviral drugs. Equally important is the concept of variability, which allows these viruses to evade immunity and antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Household transmission is a primary source of SARS-CoV-2 spread. We used COVID-19 epidemiologic investigation data and viral genome analysis data collected in the city of Kyoto, Japan, during January 2020-June 2021 to evaluate the effects of different settings and viral strains on SARS-CoV-2 transmission. Epidemiologic investigations of 5,061 COVID-19 cases found that the most common category for close contact was within households (35.3%); this category also had the highest reverse transcription PCR positivity. The prevalent viral lineage shifted from B.1.1.214 in the third wave to the Alpha variant in the fourth wave. The proportion of secondary cases associated with households also increased from the third to fourth waves (27% vs. 29%). Among 564 contacts from 206 households, Alpha variant was significantly associated with household transmission (odds ratio 1.52, 95% CI 1.06-2.18) compared with B.1.1.214. Public health interventions targeting household contacts and specific variants could help control SARS-CoV-2 transmission. [ABSTRACT FROM AUTHOR]

With the rapid development of the genomic sequence data for the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants Delta (B.1.617.2) and Omicron (B.1.1.529), it is vital to successfully identify mutations within the genome. The main objective of the study is to investigate the full-length genome mutation analysis of 157 SARS-CoV-2 and its variant Delta and Omicron isolates. This study also provides possible effects at the structural level to understand the role of mutations and new insights into the evolution of COVID-19 and evaluates the differential level analysis in viral genome sequence among different nations. We have also tried to offer a mutation snapshot for these differences that could help in vaccine formulation. This study utilizes a unique and efficient method of targeting the stable genes for the drug discovery approach. Complete genome sequence information of SARS-CoV-2, Delta, and Omicron from online resources were used to predict structure domain identification, data mining, and screening; employing different bioinformatics tools. BioEdit software was used to perform their genomic alignments across countries and a phylogenetic tree as per the confidence of 500 bootstrapping values was constructed. Heterozygosity ratios were determined in-silico. A minimum spanning network (MSN) of selected populations was determined by Bruvo's distance role-based framework. Out of all 157 different strains of SARS-CoV-2 and its variants, and their complete genome sequences from different countries, Corona nucleoca and DUF5515 were observed to be the most conserved domains. All genomes obtained changes in comparison to the Wuhan-Hu-1 strain, mainly in the TRS region (CUAAAC or ACGAAC). We discovered 596 mutations in all genes, with the highest number (321) found in ORF1ab (QHD43415.1), or TRS site mutations found only in ORF7a (1) and ORF10 (2). The Omicron variant has 30 mutations in the Spike protein and has a higher alpha-helix shape (23.46%) than the Delta version (22.03%). T478 was also discovered to be a prevalent polymorphism in Delta and Omicron variations, as well as genomic gaps ranging from 45 to 65aa. All 157 sequences contained variations and conformed to Nei's Genetic distance. We discovered heterozygosity (Hs) 0.01, mean anticipated Hs 0.32, the genetic diversity index (GDI) 0.01943989, and GD within population 0.01266951. The Hedrick value was 0.52324978, the GD coefficient was 0.52324978, the average Hs was 0.01371452, and the GD coefficient was 0.52324978. Among other countries, Brazil has the highest standard error (SE) rate (1.398), whereas Japan has the highest ratio of Nei's gene diversity (0.01). The study's findings will assist in comprehending the shape and kind of complete genome, their streaming genomic sequences, and mutations in various additions of SARS-CoV-2, as well as its different variant strains like Omicron. These results will provide a scientific basis to design the vaccines and understand the genomic study of these viruses. [ABSTRACT FROM AUTHOR]

Abstract Background Coronaviruses can be isolated from bats, civets, pangolins, birds and other wild animals. As an animal-origin pathogen, coronavirus can cross species barrier and cause pandemic in humans. In this study, a deep learning model for early prediction of pandemic risk was proposed based on the sequences of viral genomes. Methods A total of 3257 genomes were downloaded from the Coronavirus Genome Resource Library. We present a deep learning model of cross-species coronavirus infection that combines a bidirectional gated recurrent unit network with a one-dimensional convolution. The genome sequence of animal-origin coronavirus was directly input to extract features and predict pandemic risk. The best performances were explored with the use of pre-trained DNA vector and attention mechanism. The area under the receiver operating characteristic curve (AUROC) and the area under precision-recall curve (AUPR) were used to evaluate the predictive models. Results The six specific models achieved good performances for the corresponding virus groups (1 for AUROC and 1 for AUPR). The general model with pre-training vector and attention mechanism provided excellent predictions for all virus groups (1 for AUROC and 1 for AUPR) while those without pre-training vector or attention mechanism had obviously reduction of performance (about 5–25%). Re-training experiments showed that the general model has good capabilities of transfer learning (average for six groups: 0.968 for AUROC and 0.942 for AUPR) and should give reasonable prediction for potential pathogen of next pandemic. The artificial negative data with the replacement of the coding region of the spike protein were also predicted correctly (100% accuracy). With the application of the Python programming language, an easy-to-use tool was created to implements our predictor. Conclusions Robust deep learning model with pre-training vector and attention mechanism mastered the features from the whole genomes of animal-origin coronaviruses and could predict the risk of cross-species infection for early warning of next pandemic. Graphical Abstract

African swine fever (ASF) outbreak have caused tremendous economic loss to the pig industry in China since its emergence in August 2018. Previous studies revealed that many published sequences are not suitable for detailed analyses due to the lack of data regarding quality parameters and methodology, and outdated annotations. Thus, high-quality genomes of highly pathogenic strains that can be used as references for early Chinese ASF outbreaks are still lacking, and little is known about the features of intra-host variants of ASF virus (ASFV). In this study, a full genome sequencing of clinical samples from the first ASF outbreak in Guangdong in 2018 was performed using MGI (MGI Tech Co., Ltd., Shenzhen, China) and Nanopore sequencing platforms, followed by Sanger sequencing to verify the variations. With 22 sequencing corrections, we obtained a high-quality genome of one of the earliest virulent isolates, GZ201801_2. After proofreading, we improved (add or modify) the annotations of this isolate using the whole genome alignment with Georgia 2007/1. Based on the complete genome sequence, we constructed the methylation profiles of early ASFV strains in China and predicted the potential 5mC and 6mA methylation sites, which are likely involved in metabolism, transcription, and replication. Additionally, the intra-host single nucleotide variant distribution and mutant allele frequency in the clinical samples of early strain were determined for the first time and found a strong preference for A and T substitution mutation, non-synonymous mutations, and mutations that resulted in amino acid substitutions into Lysine. In conclusion, this study provides a high-quality genome sequence, updated genome annotation, methylation profile, and mutation spectrum of early ASFV strains in China, thereby providing a reference basis for further studies on the evolution, transmission, and virulence of ASFV.

Viruses are ubiquitous in humans and various environments and continually mutate themselves. Identifying viruses in an environment without cultivation is challenging; however, promoting the screening of novel viruses and expanding the knowledge of viral space is essential. Homology-based methods that identify viruses using known viral genomes rely on sequence alignments, making it difficult to capture remote homologs of the known viruses. To accurately capture viral signals from metagenomic samples, models are needed to understand the patterns encoded in the viral genomes. In this study, we developed a hierarchical BERT model named ViBE to detect eukaryotic viruses from metagenome sequencing data and classify them at the order level. We pre-trained ViBE using read-like sequences generated from the virus reference genomes and derived three fine-tuned models that classify paired-end reads to orders for eukaryotic deoxyribonucleic acid viruses and eukaryotic ribonucleic acid viruses. ViBE achieved higher recall than state-of-the-art alignment-based methods while maintaining comparable precision. ViBE outperformed state-of-the-art alignment-free methods for all test cases. The performance of ViBE was also verified using real sequencing datasets, including the vaginal virome. [ABSTRACT FROM AUTHOR]

Viral diseases affecting the essential oil rose, which is a valuable object of agricultural production, may have a significant negative impact on the economic value of this crop. Hence, the study and control of potentially dangerous viruses is essential to improving the quality of cultivars of this raw plant material, to enable production of valuable derivatives. The diversity of viruses affecting Rosa L. plants manifests itself in their conditional division into those that are specific to this crop, and those that are hosted by other plants. Representatives of both groups are found in different countries, however, a low number of viruses identified have been thoroughly studied through the use of experimental methods. In particular, with regard to many viruses, the issue of their spread remains open. The viruses infecting Rosa L. plants along with other crops are described in the literature in detail, as the range of hosts they affect is rather wide and well-studied. It is also possible to single out the three most significant viruses affecting this host—Prunus necrotic ringspot virus, Apple mosaic virus and Arabis mosaic virus which individually, or collectively, cause viral diseases that manifest themselves in mosaic symptoms. The most likely mechanisms for the spread of the Rosa L. species viruses are vegetative propagation procedures and transmission by various pests. These presumptions underlie viral infection control methods, including a well-thought-out planting scheme and provision of accurate plant care, which considers plant disinfection, disease monitoring associated with diagnostics and obtaining virus-free material through biotechnology techniques. [ABSTRACT FROM AUTHOR]

A novel nidovirus, CSBV Bces-Po19, was isolated from the marine fish, Japanese flounder (Paralichthys olivaceus). The viral genome was 26,597 nucleotides long and shared 98.62% nucleotide identity with CSBV WHQSR4345. PacBio Sequel and Illumina sequencing were used to perform full-length transcriptome sequencing on CSBV Bces-Po19-sensitive (S) and -resistant (R) Japanese flounder. The results of negative staining revealed bacilliform and spherical virions. There were in total 1444 different genes between CSBV Bces-Po19 S and R groups, with 935 being up-regulated and 513 being down-regulated. Metabolism-, immune-, and RNA-related pathways were significantly enriched. Furthermore, CSBV Bces-Po19 infection induced alternative splicing (AS) events in Japanese flounder; the S group had a higher numbers of AS events (12,352) than the R group (11,452). The number of long non-coding RNA (lncRNA) in the S group, on the other hand, was significantly lower than in the R group. In addition to providing valuable information that sheds more light on CSBV Bces-Po19 infection, these research findings provide further clues for CSBV Bces-Po19 prevention and treatment. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Northwest A & F University - Natural Science Edition is the property of Editorial Department of Journal of Northwest A&F University (Natural Science Edition) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

JC polyomavirus (JCPyV) is the causative agent of the fatal, incurable, neurological disease, progressive multifocal leukoencephalopathy (PML). The virus is present in most of the adult population as a persistent, asymptotic infection in the kidneys. During immunosuppression, JCPyV reactivates and invades the central nervous system. A main predictor of disease outcome is determined by mutations within the hypervariable region of the viral genome. In patients with PML, JCPyV undergoes genetic rearrangements in the noncoding control region (NCCR). The outcome of these rearrangements influences transcription factor binding to the NCCR, orchestrating viral gene transcription. This study examines 989 NCCR sequences from patient isolates deposited in GenBank to determine the frequency of mutations based on patient isolation site and disease status. The transcription factor binding sites (TFBS) were also analyzed to understand how these rearrangements could influence viral transcription. It was determined that the number of TFBS was significantly higher in PML samples compared to non-PML samples. Additionally, TFBS that could promote JCPyV infection were more prevalent in samples isolated from the cerebrospinal fluid compared to other locations. Collectively, this research describes the extent of mutations in the NCCR that alter TFBS and how they correlate with disease outcome. [ABSTRACT FROM AUTHOR]

Viral disease in potatoes has been a major problem in potato production worldwide. In addition to the potential risk of introducing new diseases in new areas, viral-disease epidemics/pandemics can be initiated by "spillover" of indigenous viruses from infected alternative hosts into introduced cultivars. To investigate the tendency of potential viral infection/resistance, we analyzed the viromes of introduced and indigenous varieties of potatoes among different tissues using RNA-seq libraries. Bioinformatics analyses revealed that potato viruses PVM, PVY, and PVS were dominant and the most frequently identified viruses infecting potato virus-free plants in the field, and showed an infection bias between introduced and indigenous cultivars. PVY and PVS were the major viruses in introduced varieties, whereas PVM showed an extraordinarily high percentage in the indigenous variety. Other three common viruses, PVH, potato mop-top virus, and potato leafroll virus were identified specifically in the indigenous variety. There was a tendency for tissue-specific infection and sequence variation in viruses: underground parts (tubers, roots) harbored more unusual viruses, and tubers harbored relatively more variation with a high frequency of single nucleotide polymorphisms than other tissues. Taken together, our study provides a comprehensive overview of the composition, distribution, and sequence variation of viruses between introduced and indigenous varieties of potatoes. [ABSTRACT FROM AUTHOR]