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Trends in Microbiology May 2019Infections of mammals with pathogenic viruses occur mostly in the polymicrobial environment of mucosal surfaces or the skin. In recent years our understanding of immune... (Review)
Review
Infections of mammals with pathogenic viruses occur mostly in the polymicrobial environment of mucosal surfaces or the skin. In recent years our understanding of immune modulation by the commensal microbiota has increased dramatically. The microbiota is today accepted as the prime educator and maintainer of innate and adaptive immune functions. It became further apparent that some viral pathogens profit from the presence of commensal bacteria and their metabolites, especially in the intestinal tract. We further learned that the composition and abundance of the microbiota can change as a consequence of acute and chronic viral infections. Here we discuss recent developments in our understanding of the triangular relationship of virus, host, and microbiota under experimental infection settings.
Topics: Animals; Bacteria; DNA Viruses; Disease Models, Animal; Gastrointestinal Microbiome; Humans; Immunity, Innate; Intestines; Microbiota; Mucous Membrane; Symbiosis; Virus Diseases
PubMed: 30638775
DOI: 10.1016/j.tim.2018.12.004 -
International Journal of Molecular... Dec 2015Glycosylation of surface molecules is a key feature of several eukaryotic viruses, which use the host endoplasmic reticulum/Golgi apparatus to add carbohydrates to their... (Review)
Review
Glycosylation of surface molecules is a key feature of several eukaryotic viruses, which use the host endoplasmic reticulum/Golgi apparatus to add carbohydrates to their nascent glycoproteins. In recent years, a newly discovered group of eukaryotic viruses, belonging to the Nucleo-Cytoplasmic Large DNA Virus (NCLDV) group, was shown to have several features that are typical of cellular organisms, including the presence of components of the glycosylation machinery. Starting from initial observations with the chlorovirus PBCV-1, enzymes for glycan biosynthesis have been later identified in other viruses; in particular in members of the Mimiviridae family. They include both the glycosyltransferases and other carbohydrate-modifying enzymes and the pathways for the biosynthesis of the rare monosaccharides that are found in the viral glycan structures. These findings, together with genome analysis of the newly-identified giant DNA viruses, indicate that the presence of glycogenes is widespread in several NCLDV families. The identification of autonomous viral glycosylation machinery leads to many questions about the origin of these pathways, the mechanisms of glycan production, and eventually their function in the viral replication cycle. The scope of this review is to highlight some of the recent results that have been obtained on the glycosylation systems of the large DNA viruses, with a special focus on the enzymes involved in nucleotide-sugar production.
Topics: Animals; DNA Viruses; Evolution, Molecular; Glycoproteins; Glycosylation; Glycosyltransferases; Polysaccharides; Protein Processing, Post-Translational; Viral Proteins
PubMed: 26690138
DOI: 10.3390/ijms161226169 -
Cell Reports Methods Feb 2024Herpesviruses are large DNA viruses and include important human and veterinary pathogens. Their genomes can be cloned as bacterial artificial chromosomes (BACs) and...
Herpesviruses are large DNA viruses and include important human and veterinary pathogens. Their genomes can be cloned as bacterial artificial chromosomes (BACs) and genetically engineered in Escherichia coli using BAC recombineering methods. While the recombineering methods are efficient, the initial BAC-cloning step remains laborious. To overcome this limitation, we have developed a simple, rapid, and efficient BAC-cloning method based on single-step transformation-associated recombination (STAR) in Saccharomyces cerevisiae. The linear viral genome is directly integrated into a vector comprising a yeast centromeric plasmid and a BAC replicon. Following transfer into E. coli, the viral genome can be modified using standard BAC recombineering techniques. We demonstrate the speed, fidelity, and broad applicability of STAR by cloning two strains of both rat cytomegalovirus (a betaherpesvirus) and Kaposi's sarcoma-associated herpesvirus (a gammaherpesvirus). STAR cloning facilitates the functional genetic analysis of herpesviruses and other large DNA viruses and their use as vaccines and therapeutic vectors.
Topics: Humans; Cloning, Molecular; Recombination, Genetic; Escherichia coli; Plasmids; Gammaherpesvirinae; Herpesvirus 8, Human
PubMed: 38266652
DOI: 10.1016/j.crmeth.2024.100696 -
Annual Review of Virology Sep 2022Subcellular organization is essential for life. Cells organize their functions into organelles to concentrate their machinery and supplies for optimal efficiency.... (Review)
Review
Subcellular organization is essential for life. Cells organize their functions into organelles to concentrate their machinery and supplies for optimal efficiency. Likewise, viruses organize their replication machinery into compartments or factories within their host cells for optimal replicative efficiency. In this review, we discuss how DNA viruses that infect both eukaryotic cells and bacteria assemble replication compartments for synthesis of progeny viral DNA and transcription of the viral genome. Eukaryotic DNA viruses assemble replication compartments in the nucleus of the host cell while DNA bacteriophages assemble compartments called phage nuclei in the bacterial cytoplasm. Thus, DNA viruses infecting host cells from different domains of life share common replication strategies.
Topics: Bacteria; Bacteriophages; Cell Nucleus; DNA Viruses; DNA, Bacterial; DNA, Viral; Eukaryota; Eukaryotic Cells; Virus Replication; Viruses
PubMed: 36173697
DOI: 10.1146/annurev-virology-012822-125828 -
Virology Journal May 2022The thermal stability of viruses in gelatin liquid formulations for medical research and application is poorly understood and this study aimed to examine the thermal...
BACKGROUND
The thermal stability of viruses in gelatin liquid formulations for medical research and application is poorly understood and this study aimed to examine the thermal stability of 4 enveloped and nonenveloped DNA and RNA viruses in hydrolyzed gelatin liquid formulations.
METHODS
Bovine herpesvirus (BHV) was used as a model virus to examine the molecular weight (MW), concentration and gelatin type and to optimize virus stability in liquid formulations at 25 °C and 4 °C. Using the model virus liquid formulation, the stability of multiple enveloped and nonenveloped RNA and DNA viruses, including parainfluenza virus, reovirus (RV), BHV, and adenovirus (AdV), was monitored over up to a 30-week storage period.
RESULTS
The BHV model virus was considered stable after 3 weeks in hydrolyzed gelatin (MW: 4000) with a 0.8 LRV (log10 reduction value) at 25 °C or a 0.2 LRV at 4 °C, compared to the stabilities observed in higher MW gelatin (60,000 and 160,000) with an LRV above 1. Based on the gelatin type, BHV in alkaline-treated hydrolyzed gelatin samples were unexpectantly more stable than in acid-treated hydrolyzed gelatin sample. All four viruses exhibited stability at 4 °C for at least 8 weeks, BHV or AdV remained stable for over 30 weeks of storage, and at 25 °C, AdV and RV remained stable for 8 weeks.
CONCLUSION
The results demonstrated that 5% of 4000 MW hydrolyzed gelatin formulation can act as a relevant stabilizer for the thermal stability of viruses in medical research and application.
Topics: Adenoviridae; DNA Viruses; Gelatin; RNA Viruses; Viruses
PubMed: 35624453
DOI: 10.1186/s12985-022-01819-w -
Annual Review of Virology Sep 2022For decades, viruses have been isolated primarily from humans and other organisms. Interestingly, one of the most complex sides of the virosphere was discovered using... (Review)
Review
For decades, viruses have been isolated primarily from humans and other organisms. Interestingly, one of the most complex sides of the virosphere was discovered using free-living amoebae as hosts. The discovery of giant viruses in the early twenty-first century opened a new chapter in the field of virology. Giant viruses are included in the phylum and harbor large and complex DNA genomes (up to 2.7 Mb) encoding genes never before seen in the virosphere and presenting gigantic particles (up to 1.5 μm). Different amoebae have been used to isolate and characterize a plethora of new viruses with exciting details about novel viral biology. Through distinct isolation techniques and metagenomics, the diversity and complexity of giant viruses have astonished the scientific community. Here, we discuss the latest findings on amoeba viruses and how using these single-celled organisms as hosts has revealed entities that have remained hidden in plain sight for ages.
Topics: Amoeba; DNA Viruses; Genome, Viral; Giant Viruses; Humans; Metagenomics; Phylogeny; Viruses
PubMed: 35655338
DOI: 10.1146/annurev-virology-100520-125832 -
Proceedings of the National Academy of... Aug 2022Human cells encode up to 15 DNA polymerases with specialized functions in chromosomal DNA synthesis and damage repair. In contrast, complex DNA viruses, such as those of...
Human cells encode up to 15 DNA polymerases with specialized functions in chromosomal DNA synthesis and damage repair. In contrast, complex DNA viruses, such as those of the herpesviridae family, encode a single B-family DNA polymerase. This disparity raises the possibility that DNA viruses may rely on host polymerases for synthesis through complex DNA geometries. We tested the importance of error-prone Y-family polymerases involved in translesion synthesis (TLS) to human cytomegalovirus (HCMV) infection. We find most Y-family polymerases involved in the nucleotide insertion and bypass of lesions restrict HCMV genome synthesis and replication. In contrast, other TLS polymerases, such as the polymerase ζ complex, which extends past lesions, was required for optimal genome synthesis and replication. Depletion of either the polζ complex or the suite of insertion polymerases demonstrate that TLS polymerases suppress the frequency of viral genome rearrangements, particularly at GC-rich sites and repeat sequences. Moreover, while distinct from HCMV, replication of the related herpes simplex virus type 1 is impacted by host TLS polymerases, suggesting a broader requirement for host polymerases for DNA virus replication. These findings reveal an unexpected role for host DNA polymerases in ensuring viral genome stability.
Topics: Cytomegalovirus; DNA Damage; DNA Repair; DNA Replication; DNA Viruses; DNA-Directed DNA Polymerase; Genome, Viral; Humans; Virus Replication
PubMed: 35947614
DOI: 10.1073/pnas.2203203119 -
Frontiers in Cellular and Infection... 2017Herpesviruses are a large group of DNA viruses infecting mainly vertebrates. Murine gammaherpesvirus 68 (MHV68) is often used as a model in studies of the pathogenesis...
Herpesviruses are a large group of DNA viruses infecting mainly vertebrates. Murine gammaherpesvirus 68 (MHV68) is often used as a model in studies of the pathogenesis of clinically important human gammaherpesviruses such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. This rodent virus appears to be geographically widespread; however, its natural transmission cycle is unknown. Following detection of MHV68 in field-collected ticks, including isolation of the virus from tick salivary glands and ovaries, we investigated whether MHV68 is a tick-borne virus. Uninfected ticks were shown to acquire the virus by feeding on experimentally infected laboratory mice. The virus survived tick molting, and the molted ticks transmitted the virus to uninfected laboratory mice on which they subsequently fed. MHV68 was isolated from the tick salivary glands, consistent with transmission via tick saliva. The virus survived in ticks without loss of infectivity for at least 120 days, and subsequently was transmitted vertically from one tick generation to the next, surviving more than 500 days. Furthermore, the F1 generation (derived from F0 infected females) transmitted MHV68 to uninfected mice on which they fed, with MHV68 M3 gene transcripts detected in blood, lung, and spleen tissue of mice on which F1 nymphs and F1 adults engorged. These experimental data fulfill the transmission criteria that define an arthropod-borne virus (arbovirus), the largest biological group of viruses. Currently, African swine fever virus (ASFV) is the only DNA virus recognized as an arbovirus. Like ASFV, MHV68 showed evidence of pathogenesis in ticks. Previous studies have reported MHV68 in free-living ticks and in mammals commonly infested with , and neutralizing antibodies to MHV68 have been detected in large mammals (e.g., deer) including humans. Further studies are needed to determine if these reports are the result of tick-borne transmission of MHV68 in nature, and whether humans are at risk of infection.
Topics: African Swine Fever Virus; Animals; Arboviruses; Cell Line; DNA, Viral; Disease Models, Animal; Female; Gammaherpesvirinae; Genome, Viral; Ixodes; Lung; Mice; Salivary Glands; Spleen; Tick-Borne Diseases; Ticks
PubMed: 29164067
DOI: 10.3389/fcimb.2017.00458 -
Annals of the New York Academy of... Apr 2015Diverse eukaryotes including animals and protists are hosts to a broad variety of viruses with double-stranded (ds) DNA genomes, from the largest known viruses, such as... (Review)
Review
Diverse eukaryotes including animals and protists are hosts to a broad variety of viruses with double-stranded (ds) DNA genomes, from the largest known viruses, such as pandoraviruses and mimiviruses, to tiny polyomaviruses. Recent comparative genomic analyses have revealed many evolutionary connections between dsDNA viruses of eukaryotes, bacteriophages, transposable elements, and linear DNA plasmids. These findings provide an evolutionary scenario that derives several major groups of eukaryotic dsDNA viruses, including the proposed order "Megavirales," adenoviruses, and virophages from a group of large virus-like transposons known as Polintons (Mavericks). The Polintons have been recently shown to encode two capsid proteins, suggesting that these elements lead a dual lifestyle with both a transposon and a viral phase and should perhaps more appropriately be named polintoviruses. Here, we describe the recently identified evolutionary relationships between bacteriophages of the family Tectiviridae, polintoviruses, adenoviruses, virophages, large and giant DNA viruses of eukaryotes of the proposed order "Megavirales," and linear mitochondrial and cytoplasmic plasmids. We outline an evolutionary scenario under which the polintoviruses were the first group of eukaryotic dsDNA viruses that evolved from bacteriophages and became the ancestors of most large DNA viruses of eukaryotes and a variety of other selfish elements. Distinct lines of origin are detectable only for herpesviruses (from a different bacteriophage root) and polyoma/papillomaviruses (from single-stranded DNA viruses and ultimately from plasmids). Phylogenomic analysis of giant viruses provides compelling evidence of their independent origins from smaller members of the putative order "Megavirales," refuting the speculations on the evolution of these viruses from an extinct fourth domain of cellular life.
Topics: Animals; Bacteriophages; DNA; DNA Transposable Elements; DNA Viruses; DNA, Viral; Eukaryota; Humans; Models, Genetic; Phylogeny
PubMed: 25727355
DOI: 10.1111/nyas.12728 -
Journal of Virology Dec 2017Our genomes are dominated by repetitive elements. The majority of these elements derive from retrotransposons, which expand throughout the genome through a process of... (Review)
Review
Our genomes are dominated by repetitive elements. The majority of these elements derive from retrotransposons, which expand throughout the genome through a process of reverse transcription and integration. Short interspersed nuclear elements, or SINEs, are an abundant class of retrotransposons that are transcribed by RNA polymerase III, thus generating exclusively noncoding RNA (ncRNA) that must hijack the machinery required for their transposition. SINE loci are generally transcriptionally repressed in somatic cells but can be robustly induced upon infection with multiple DNA viruses. Recent research has focused on the gene expression and signaling events that are modulated by SINE ncRNAs, particularly during gammaherpesvirus infection. Here, we review the biology of these SINE ncRNAs, explore how DNA virus infection may lead to their induction, and describe how novel gene regulatory and immune-related functions of these ncRNAs may impact the viral life cycle.
Topics: Animals; DNA Viruses; Gene Expression; Gene Expression Regulation, Viral; Host-Pathogen Interactions; Humans; Mice; RNA Polymerase III; RNA, Untranslated; Retroelements; Short Interspersed Nucleotide Elements; Signal Transduction
PubMed: 28931686
DOI: 10.1128/JVI.00982-17