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Trends in Biotechnology Dec 2020Microfluidics has proven to be a powerful tool for probing biology at the single-cell level. However, it is only in the past 5 years that single-cell microfluidics has... (Review)
Review
Microfluidics has proven to be a powerful tool for probing biology at the single-cell level. However, it is only in the past 5 years that single-cell microfluidics has been used in the field of virology. An array of strategies based on microwells, microvalves, and droplets is now available for tracking viral infection dynamics, identifying cell subpopulations with particular phenotypes, as well as high-throughput screening. The insights into the virus-host interactions gained at the single-cell level are unprecedented and usually inaccessible by population-based experiments. Therefore, single-cell microfluidics, which opens new avenues for mechanism elucidation and development of antiviral therapeutics, would be a valuable tool for the study of viral pathogenesis.
Topics: High-Throughput Screening Assays; Microfluidics; Single-Cell Analysis; Virology
PubMed: 32430227
DOI: 10.1016/j.tibtech.2020.04.010 -
Nature May 2023CrAssphage and related viruses of the order Crassvirales (hereafter referred to as crassviruses) were originally discovered by cross-assembly of metagenomic sequences....
CrAssphage and related viruses of the order Crassvirales (hereafter referred to as crassviruses) were originally discovered by cross-assembly of metagenomic sequences. They are the most abundant viruses in the human gut, are found in the majority of individual gut viromes, and account for up to 95% of the viral sequences in some individuals. Crassviruses are likely to have major roles in shaping the composition and functionality of the human microbiome, but the structures and roles of most of the virally encoded proteins are unknown, with only generic predictions resulting from bioinformatic analyses. Here we present a cryo-electron microscopy reconstruction of Bacteroides intestinalis virus ΦcrAss001, providing the structural basis for the functional assignment of most of its virion proteins. The muzzle protein forms an assembly about 1 MDa in size at the end of the tail and exhibits a previously unknown fold that we designate the 'crass fold', that is likely to serve as a gatekeeper that controls the ejection of cargos. In addition to packing the approximately 103 kb of virus DNA, the ΦcrAss001 virion has extensive storage space for virally encoded cargo proteins in the capsid and, unusually, within the tail. One of the cargo proteins is present in both the capsid and the tail, suggesting a general mechanism for protein ejection, which involves partial unfolding of proteins during their extrusion through the tail. These findings provide a structural basis for understanding the mechanisms of assembly and infection of these highly abundant crassviruses.
Topics: Humans; Capsid; Cryoelectron Microscopy; DNA Viruses; Virion; Virus Assembly; Intestines; Viral Proteins; Protein Unfolding; Protein Folding
PubMed: 37138077
DOI: 10.1038/s41586-023-06019-2 -
Nature Immunology Jul 2019
Topics: Allergy and Immunology; Animals; Famous Persons; History, 20th Century; Humans; Mice; Virology
PubMed: 31182808
DOI: 10.1038/s41590-019-0428-8 -
Cellular Microbiology Aug 2019
Topics: Animals; Argentina; France; History, 20th Century; History, 21st Century; Humans; Insecta; Molecular Biology; Virology
PubMed: 31112322
DOI: 10.1111/cmi.13061 -
BMC Microbiology Jun 2021Phages are one of the key components in the structure, dynamics, and interactions of microbial communities in different bins. It has a clear impact on human health and... (Review)
Review
Phages are one of the key components in the structure, dynamics, and interactions of microbial communities in different bins. It has a clear impact on human health and the food industry. Bacteriophage characterization using in vitro approaches are time/cost consuming and laborious tasks. On the other hand, with the advent of new high-throughput sequencing technology, the development of a powerful computational framework to characterize the newly identified bacteriophages is inevitable for future research. Machine learning includes powerful techniques that enable the analysis of complex datasets for knowledge discovery and pattern recognition. In this study, we have conducted a comprehensive review of machine learning methods application using different types of features were applied in various aspects of bacteriophage research including, automated curation, identification, classification, host species recognition, virion protein identification, and life cycle prediction. Moreover, potential limitations and advantages of the developed frameworks were discussed.
Topics: Bacteriophages; Machine Learning; Virology
PubMed: 34174831
DOI: 10.1186/s12866-021-02256-5 -
Frontiers in Immunology 2022Viroporins are virally encoded transmembrane proteins that are essential for viral pathogenicity and can participate in various stages of the viral life cycle, thereby... (Review)
Review
Viroporins are virally encoded transmembrane proteins that are essential for viral pathogenicity and can participate in various stages of the viral life cycle, thereby promoting viral proliferation. Viroporins have multifaceted effects on host cell biological functions, including altering cell membrane permeability, triggering inflammasome formation, inducing apoptosis and autophagy, and evading immune responses, thereby ensuring that the virus completes its life cycle. Viroporins are also virulence factors, and their complete or partial deletion often reduces virion release and reduces viral pathogenicity, highlighting the important role of these proteins in the viral life cycle. Thus, viroporins represent a common drug-protein target for inhibiting drugs and the development of antiviral therapies. This article reviews current studies on the functions of viroporins in the viral life cycle and their regulation of host cell responses, with the aim of improving the understanding of this growing family of viral proteins.
Topics: Cell Membrane Permeability; Membrane Proteins; Viral Proteins; Viroporin Proteins; Viruses
PubMed: 35720341
DOI: 10.3389/fimmu.2022.890549 -
Nature Communications Dec 2023Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor a vaccine are available. ZIKV is an enveloped RNA virus, replicating in the...
Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor a vaccine are available. ZIKV is an enveloped RNA virus, replicating in the cytoplasm in close association with ER membranes. Here, we isolate ER membranes from ZIKV-infected cells and determine their proteome. Forty-six host cell factors are enriched in ZIKV remodeled membranes, several of these having a role in redox and methylation pathways. Four proteins are characterized in detail: thioredoxin reductase 1 (TXNRD1) contributing to folding of disulfide bond containing proteins and modulating ZIKV secretion; aldo-keto reductase family 1 member C3 (AKR1C3), regulating capsid protein abundance and thus, ZIKV assembly; biliverdin reductase B (BLVRB) involved in ZIKV induced lipid peroxidation and increasing stability of viral transmembrane proteins; adenosylhomocysteinase (AHCY) indirectly promoting mA methylation of ZIKV RNA by decreasing the level of S- adenosyl homocysteine and thus, immune evasion. These results highlight the involvement of redox and methylation enzymes in the ZIKV life cycle and their accumulation at virally remodeled ER membranes.
Topics: Humans; Zika Virus; Zika Virus Infection; Methylation; Proviruses; Virus Replication; Viral Proteins; Oxidation-Reduction
PubMed: 38052817
DOI: 10.1038/s41467-023-43665-6 -
Frontiers in Immunology 2022nucleopolyhedrovirus (BmNPV) is one of the most serious pathogens and causes serious economic losses in sericulture. At present, there is no epigenetic modification of...
nucleopolyhedrovirus (BmNPV) is one of the most serious pathogens and causes serious economic losses in sericulture. At present, there is no epigenetic modification of BmNPV transcripts, especially of m6A, and this modification mediates diverse cellular and viral functions. This study showed that m6A modifications are widespread in BmNPV transcripts in virally infected cells and the identified m6A peaks with a conserved RRACH sequence. m6A sites predominantly appear in the coding sequences (CDS) and the 3'-end of CDS. About 37% of viral genes with m6A sites deleted from the viral genome did not produce any infectious virions in KOV-transfected cells. Among the viral genes related to replication and proliferation, mRNA was identified with a higher m6A level than other viral genes. The m6A sites in the mRNA may be negatively related to the protein expression. Viral replication was markedly inhibited in cells overexpressed with BmYTHDF3 in a dose-dependent manner, and a contrary effect was found in si-BmYTHDF3-transfected cells. Collectively, the identification of putative m6A modification in BmNPV transcripts provides a foundation for comprehensively understanding the viral infection, replication, and pathobiology in silkworms.
Topics: Animals; Bombyx; Nucleopolyhedroviruses; RNA, Messenger; Virus Diseases
PubMed: 35371067
DOI: 10.3389/fimmu.2022.869313 -
Chemical Reviews Feb 2020Uncovering the mechanisms of virus infection and assembly is crucial for preventing the spread of viruses and treating viral disease. The technique of single-virus... (Review)
Review
Uncovering the mechanisms of virus infection and assembly is crucial for preventing the spread of viruses and treating viral disease. The technique of single-virus tracking (SVT), also known as single-virus tracing, allows one to follow individual viruses at different parts of their life cycle and thereby provides dynamic insights into fundamental processes of viruses occurring in live cells. SVT is typically based on fluorescence imaging and reveals insights into previously unreported infection mechanisms. In this review article, we provide the readers a broad overview of the SVT technique. We first summarize recent advances in SVT, from the choice of fluorescent labels and labeling strategies to imaging implementation and analytical methodologies. We then describe representative applications in detail to elucidate how SVT serves as a valuable tool in virological research. Finally, we present our perspectives regarding the future possibilities and challenges of SVT.
Topics: Animals; Humans; Virology; Virus Diseases; Virus Physiological Phenomena
PubMed: 31951121
DOI: 10.1021/acs.chemrev.9b00692 -
Annals of Gastroenterology 2022Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, and is attributable mainly to viral hepatitis, alcohol and nonalcoholic fatty liver disease.
BACKGROUND
Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, and is attributable mainly to viral hepatitis, alcohol and nonalcoholic fatty liver disease.
METHODS
Three hundred Greek patients diagnosed with HCC between 2000 and 2019 were retrospectively evaluated for patient and HCC characteristics. Patients were classified as before 2011 (A) or after 2011 (B) and HCC risk factors were compared with historic Greek cohorts.
RESULTS
The median age was 64 years and 86% were male; 45% had chronic hepatitis B virus (HBV) infection, 26% chronic hepatitis C virus (HCV) infection, and 30% non-viral liver diseases (nvLD). No change was observed among liver diseases between periods A and B. However, there was a trend towards a decrease in virally and an increase in non-virally induced HCC (P=0.075). Patients in period B (vs. A) were more likely to be diagnosed with fewer (<3, P=0.006) and smaller (<3 cm, P=0.005) nodules. Compared with 1558 Greek HCC patients from 1974-2000, there was a decrease in HBV and an increase in HCV and nvLD-related HCCs (P<0.001).
CONCLUSIONS
In Greece, after 2000, there was a decrease in the proportion of HBV and an increase in the proportion of HCV and nvLD-related HCC, while over the last 2 decades there has been a trend towards a decrease in virally and an increase in non-virally induced HCC. Since 2011, HCC is being diagnosed at an earlier stage, possibly reflecting improved surveillance strategies.
PubMed: 34987294
DOI: 10.20524/aog.2021.0680