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Journal of Virology Jul 2023Parvoviruses are among the smallest and superficially simplest animal viruses, infecting a broad range of hosts, including humans, and causing some deadly infections. In... (Review)
Review
The Structures and Functions of Parvovirus Capsids and Missing Pieces: the Viral DNA and Its Packaging, Asymmetrical Features, Nonprotein Components, and Receptor or Antibody Binding and Interactions.
Parvoviruses are among the smallest and superficially simplest animal viruses, infecting a broad range of hosts, including humans, and causing some deadly infections. In 1990, the first atomic structure of the canine parvovirus (CPV) capsid revealed a 26-nm-diameter T=1 particle made up of two or three versions of a single protein, and packaging about 5,100 nucleotides of single-stranded DNA. Our structural and functional understanding of parvovirus capsids and their ligands has increased as imaging and molecular techniques have advanced, and capsid structures for most groups within the family have now been determined. Despite those advances, significant questions remain unanswered about the functioning of those viral capsids and their roles in release, transmission, or cellular infection. In addition, the interactions of capsids with host receptors, antibodies, or other biological components are also still incompletely understood. The parvovirus capsid's apparent simplicity likely conceals important functions carried out by small, transient, or asymmetric structures. Here, we highlight some remaining open questions that may need to be answered to provide a more thorough understanding of how these viruses carry out their various functions. The many different members of the family share a capsid architecture, and while many functions are likely similar, others may differ in detail. Many of those parvoviruses have not been experimentally examined in detail (or at all in some cases), so we, therefore, focus this minireview on the widely studied protoparvoviruses, as well as the most thoroughly investigated examples of adeno-associated viruses.
Topics: Animals; Humans; Capsid; Capsid Proteins; DNA, Viral; Parvoviridae; Parvoviridae Infections; Dependovirus
PubMed: 37367301
DOI: 10.1128/jvi.00161-23 -
Antiviral Research Aug 2023Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox (formerly monkeypox). Identifying novel and potent antiviral...
Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox (formerly monkeypox). Identifying novel and potent antiviral compounds is critical to successful drug development targeting poxviruses. Here we tested two compounds, nucleoside trifluridine, and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV), mpox virus (MPXV), and cowpox virus (CPXV) in physiologically relevant primary human fibroblasts. Both compounds potently inhibited the replication of VACV, CPXV, and MPXV (MA001 2022 isolate) in plaque assays. In our recently developed assay based on a recombinant VACV expressing secreted Gaussia luciferase, they both exhibited high potency in inhibiting VACV replication with ECs in the low nanomolar range. In addition, both trifluridine and adefovir dipivoxil inhibited VACV DNA replication and downstream viral gene expression. Our results characterized trifluridine and adefovir dipivoxil as strong poxvirus antiviral compounds and further validate the VACV Gaussia luciferase assay as a highly efficient and reliable reporter tool for identifying poxvirus inhibitors. Given that both compounds are FDA-approved drugs, and trifluridine is already used to treat ocular vaccinia, further development of trifluridine and adefovir dipivoxil holds great promise in treating poxvirus infections, including mpox.
Topics: Animals; Humans; Vaccinia virus; Vaccinia; Cowpox virus; Antiviral Agents; Trifluridine; Mpox (monkeypox); Cell Line; Poxviridae
PubMed: 37270160
DOI: 10.1016/j.antiviral.2023.105651 -
Current Opinion in Oncology Nov 2023The purpose of this review is to give an overview of early clinical studies addressing the safety and efficacy of oncolytic immunovirotherapy in adults and children with... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to give an overview of early clinical studies addressing the safety and efficacy of oncolytic immunovirotherapy in adults and children with brain gliomas, and to highlight the extensive potential for the development of this therapeutic alternative.
RECENT FINDINGS
The lack of curative treatments and poor prognosis of high-grade glioma patients warrants research on innovative therapeutic alternatives such as oncolytic immunovirotherapy. Engineered modified oncolytic viruses exert both a direct lytic effect on tumor cells and a specific antitumor immune response. Early clinical trials of different DNA and RNA oncolytic viruses, mainly Herpes Simplex Virus Type-1 and adenovirus based platforms, have consistently demonstrated an acceptable safety profile, hints of efficacy and the potential of this therapy to reshape the tumor microenvironment in both adult and pediatric patients with glioma, thus constituting the basis for the development of more advanced clinical trials.
SUMMARY
The future landscape of oncolytic immunovirotherapy is still plenty of challenges and opportunities to enable its full therapeutic potential in both adult and children with brain gliomas.
Topics: Adult; Humans; Child; Glioma; Oncolytic Virotherapy; Oncolytic Viruses; Herpesvirus 1, Human; Brain; Brain Neoplasms; Tumor Microenvironment
PubMed: 37820087
DOI: 10.1097/CCO.0000000000000995 -
The Journal of Biological Chemistry Sep 2023Hepatitis B virus (HBV) is a hepatotropic DNA virus that has a very compact genome. Due to this genomic density, several distinct mechanisms are used to facilitate the...
Hepatitis B virus (HBV) is a hepatotropic DNA virus that has a very compact genome. Due to this genomic density, several distinct mechanisms are used to facilitate the viral life cycle. Recently, accumulating evidence show that G-quadruplex (G4) in different viruses play essential regulatory roles in key steps of the viral life cycle. Although G4 structures in the HBV genome have been reported, their function in HBV replication remains elusive. In this study, we treated an HBV replication-competent cell line and HBV-infected cells with the G4 structure stabilizer pyridostatin (PDS) and evaluated different HBV replication markers to better understand the role played by the G4. In both models, we found PDS had no effect on viral precore RNA (pcRNA) or pre-genomic RNA (pgRNA), but treatment did increase HBeAg/HBc ELISA reads and intracellular levels of viral core/capsid protein (HBc) in a dose-dependent manner, suggesting post-transcriptional regulation. To further dissect the mechanism of G4 involvement, we used in vitro-synthesized HBV pcRNA and pgRNA. Interestingly, we found PDS treatment only enhanced HBc expression from pgRNA but not HBeAg expression from pcRNA. Our bioinformatic analysis and CD spectroscopy revealed that pgRNA harbors a conserved G4 structure. Finally, we introduced point mutations in pgRNA to disrupt its G4 structure and observed the resulting mutant failed to respond to PDS treatment and decreased HBc level in in vitro translation assay. Taken together, our data demonstrate that HBV pgRNA contains a G4 structure that plays a vital role in the regulation of viral mRNA translation.
Topics: Humans; Capsid Proteins; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; RNA, Viral; Viral Core Proteins; Virus Replication; Cell Line; G-Quadruplexes; Protein Biosynthesis; Mutation; Aminoquinolines
PubMed: 37567479
DOI: 10.1016/j.jbc.2023.105151 -
Journal of Medical Virology May 2024Human Papillomaviruses (HPV) are a diverse family of non-enveloped dsDNA viruses that infect the skin and mucosal epithelia. Persistent HPV infections can lead to cancer... (Review)
Review
Human Papillomaviruses (HPV) are a diverse family of non-enveloped dsDNA viruses that infect the skin and mucosal epithelia. Persistent HPV infections can lead to cancer frequently involving integration of the virus into the host genome, leading to sustained oncogene expression and loss of capsid and genome maintenance proteins. Microhomology-mediated double-strand break repair, a DNA double-stranded breaks repair pathway present in many organisms, was initially thought to be a backup but it's now seen as vital, especially in homologous recombination-deficient contexts. Increasing evidence has identified microhomology (MH) near HPV integration junctions, suggesting MH-mediated repair pathways drive integration. In this comprehensive review, we present a detailed summary of both the mechanisms underlying MH-mediated repair and the evidence for its involvement in HPV integration in cancer. Lastly, we highlight the involvement of these processes in the integration of other DNA viruses and the broader implications on virus lifecycles and host innate immune response.
Topics: Humans; Papillomaviridae; Carcinogenesis; Papillomavirus Infections; Virus Integration; DNA Repair; DNA Breaks, Double-Stranded; DNA, Viral
PubMed: 38757834
DOI: 10.1002/jmv.29674 -
Travel Medicine and Infectious Disease 2023Monkeypox (Mpox) is a transmissible infection induced by the Monkeypox virus (a double-stranded DNA virus), recognised under the family orthopoxvirus genus. Monkeypox,... (Review)
Review
Monkeypox (Mpox) is a transmissible infection induced by the Monkeypox virus (a double-stranded DNA virus), recognised under the family orthopoxvirus genus. Monkeypox, like endemic diseases, is a substantial concern worldwide; thus, comprehending the pathogenesis and mutagenesis of amino acids is indispensable to combat the infection. According to the World Health Organization's report, about 89 thousand cases with 160 mortalities have been reported from 114 countries worldwide. The conventional orthopoxvirus vaccines developed on live attenuated viruses exempted any clinical validation from combating monkeypox due to inadequate immunogenicity, toxicity, instability, and multiple doses. Therefore, novel drug delivery systems come into the conception with high biological and mechanical characteristics to address the resurgence of Global Monkeypox. The edges of metallic biomaterials, novel molecules, and vaccine development in targeted therapy increase the modulation of the immune response and blockage of host-virus interaction, with enhanced stability for the antigens. Thus, this review strives to comprehend the viral cell pathogenesis concerning amino acid mutagenesis and current epidemiological standards of the Monkeypox disease across the globe. Furthermore, the review also recapitulates the various clinical challenges, current therapies, and progressive nanomedicine utilisation in the Monkeypox outbreak reinforced by various clinical trial reports. The contemporary challenges of novel drug delivery systems in Monkeypox treatment cannot be overlooked, and thus, authors have outlined the future strategies to develop successful nanomedicine to combat monkeypox. Future pandemics are inevitable but can be satisfactorily handled if we comprehend the crises, innovate, and develop cutting-edge technologies, especially by delving into frontiers like nanotechnology.
Topics: Humans; Mpox (monkeypox); Disease Outbreaks; Drug Delivery Systems; Endemic Diseases; Monkeypox virus; Orthopoxvirus
PubMed: 37633474
DOI: 10.1016/j.tmaid.2023.102636 -
Advances in Experimental Medicine and... 2024Although the smallpox virus has been eradicated worldwide, the World Health Organization (WHO) has issued a warning about the virus's potential to propagate globally.... (Review)
Review
Although the smallpox virus has been eradicated worldwide, the World Health Organization (WHO) has issued a warning about the virus's potential to propagate globally. The WHO labeled monkeypox a world public health emergency in July 2022, requiring urgent prevention and treatment. The monkeypox virus is a part of the Poxviridae family, Orthopoxvirus genus, and is accountable for smallpox, which has killed over a million people in the past. Natural hosts of the virus include squirrels, Gambian rodents, chimpanzees, and other monkeys. The monkeypox virus has transmitted to humans through primary vectors (various animal species) and secondary vectors, including direct touch with lesions, breathing particles from body fluids, and infected bedding. The viral particles are ovoid or brick-shaped, 200-250 nm in diameter, contain a single double-stranded DNA molecule, and reproduce only in the cytoplasm of infected cells. Monkeypox causes fever, cold, muscle pains, headache, fatigue, and backache. The phylogenetic investigation distinguished between two genetic clades of monkeypox: the more pathogenic Congo Basin clade and the West Africa clade. In recent years, the geographical spread of the human monkeypox virus has accelerated despite a paucity of information regarding the disease's emergence, ecology, and epidemiology. Using lesion samples and polymerase chain reaction (PCR), the monkeypox virus was diagnosed. In the USA, the improved Ankara vaccine can now be used to protect people who are at a higher risk of getting monkeypox. Antivirals that we have now work well against smallpox and may stop the spread of monkeypox, but there is no particular therapy for monkeypox.
Topics: Monkeypox virus; Animals; Humans; Mpox (monkeypox); Phylogeny
PubMed: 38801573
DOI: 10.1007/978-3-031-57165-7_6 -
Microbiome Oct 2023Activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses that regulate microbial metabolism and nutrient cycling, significantly...
BACKGROUND
Activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses that regulate microbial metabolism and nutrient cycling, significantly influencing the stability of AS systems. However, our knowledge about the diversity of viral taxonomic groups and functional traits in global AS systems is still limited. To address this gap, we investigated the global diversity and biogeography of DNA viral communities in AS systems using 85,114 viral operational taxonomic units (vOTUs) recovered from 144 AS samples collected across 54 WWTPs from 13 different countries.
RESULTS
AS viral communities and their functional traits exhibited distance-decay relationship (DDR) at the global scale and latitudinal diversity gradient (LDG) from equator to mid-latitude. Furthermore, it was observed that AS viral community and functional gene structures were largely driven by the geographic factors and wastewater types, of which the geographic factors were more important. Carrying and disseminating auxiliary metabolic genes (AMGs) associated with the degradation of polysaccharides, sulfate reduction, denitrification, and organic phosphoester hydrolysis, as well as the lysis of crucial functional microbes that govern biogeochemical cycles were two major ways by which viruses could regulate AS functions. It was worth noting that our study revealed a high abundance of antibiotic resistance genes (ARGs) in viral genomes, suggesting that viruses were key reservoirs of ARGs in AS systems.
CONCLUSIONS
Our results demonstrated the highly diverse taxonomic groups and functional traits of viruses in AS systems. Viral lysis of host microbes and virus-mediated HGT can regulate the biogeochemical and nutrient cycles, thus affecting the performance of AS systems. These findings provide important insights into the viral diversity, function, and ecology in AS systems on a global scale. Video Abstract.
Topics: Sewage; Wastewater; Viruses; Ecology; DNA Viruses; DNA
PubMed: 37865788
DOI: 10.1186/s40168-023-01672-1 -
Viruses Jun 2024Begomoviruses have emerged as destructive pathogens of crops, particularly in the tropics and subtropics, causing enormous economic losses and threatening food security.... (Review)
Review
Begomoviruses have emerged as destructive pathogens of crops, particularly in the tropics and subtropics, causing enormous economic losses and threatening food security. Epidemics caused by begomoviruses have even spread in regions and crops that were previously free from these viruses. The most seriously affected crops include cassava; cotton; grain legumes; and cucurbitaceous, malvaceous, and solanaceous vegetables. Alphasatellites, betasatellites, and deltasatellites are associated with the diseases caused by begomoviruses, but begomovirus-betasatellite complexes have played significant roles in the evolution of begomoviruses, causing widespread epidemics in many economically important crops throughout the world. This article provides an overview of the evolution, distribution, and approaches used by betasatellites in the suppression of host plant defense responses and increasing disease severity.
Topics: Begomovirus; Plant Diseases; Crops, Agricultural; Satellite Viruses; Evolution, Molecular; DNA, Satellite; Phylogeny
PubMed: 38932261
DOI: 10.3390/v16060970 -
Viruses Apr 2024Hepatitis B virus (HBV) is the etiologic agent of chronic hepatitis B, which puts at least 300 million patients at risk of developing fibrosis, cirrhosis, and... (Review)
Review
Hepatitis B virus (HBV) is the etiologic agent of chronic hepatitis B, which puts at least 300 million patients at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. HBV is a partially double-stranded DNA virus of the family. While HBV was discovered more than 50 years ago, many aspects of its replicative cycle remain incompletely understood. Central to HBV persistence is the formation of covalently closed circular DNA (cccDNA) from the incoming relaxed circular DNA (rcDNA) genome. cccDNA persists as a chromatinized minichromosome and is the major template for HBV gene transcription. Here, we review how cccDNA and the viral minichromosome are formed and how viral gene transcription is regulated and highlight open questions in this area of research.
Topics: Hepatitis B virus; DNA, Circular; Humans; DNA, Viral; Virus Replication; Viral Transcription; Gene Expression Regulation, Viral; Transcription, Genetic; Genome, Viral; Hepatitis B, Chronic; Hepatitis B; DNA Replication
PubMed: 38675950
DOI: 10.3390/v16040609