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Viruses Aug 2019Autophagy is a catabolic biological process in the body. By targeting exogenous microorganisms and aged intracellular proteins and organelles and sending them to the... (Review)
Review
Autophagy is a catabolic biological process in the body. By targeting exogenous microorganisms and aged intracellular proteins and organelles and sending them to the lysosome for phagocytosis and degradation, autophagy contributes to energy recycling. When cells are stimulated by exogenous pathogenic microorganisms such as viruses, activation or inhibition of autophagy is often triggered. As autophagy has antiviral effects, many viruses may escape and resist the process by encoding viral proteins. At the same time, viruses can also use autophagy to enhance their replication or increase the persistence of latent infections. Here, we give a brief overview of autophagy and DNA viruses and comprehensively review the known interactions between human and animal DNA viruses and autophagy and the role and mechanisms of autophagy in viral DNA replication and DNA virus-induced innate and acquired immunity.
Topics: Adaptive Immunity; Adenoviridae; Animals; Autophagosomes; Autophagy; DNA Viruses; Herpesviridae; Host Microbial Interactions; Humans; Immune Evasion; Immunity, Innate; Lysosomes; Papillomaviridae; Phagocytosis; Signal Transduction; Viral Proteins; Virus Replication
PubMed: 31450758
DOI: 10.3390/v11090776 -
Annual Review of Virology Sep 2018DNA viruses are linked to many infectious diseases and contribute significantly to human morbidity and mortality worldwide. Moreover, DNA viral infections are usually... (Review)
Review
DNA viruses are linked to many infectious diseases and contribute significantly to human morbidity and mortality worldwide. Moreover, DNA viral infections are usually lifelong and hard to eradicate. Under certain circumstances, these viruses can cause fatal disease, especially in children and immunocompromised patients. An efficient innate immune response against these viruses is critical, not only as the first line of host defense against viral infection but also for mounting more specific and robust adaptive immunity against the virus. Recognition of the viral DNA genome is the very first step of this whole process and is crucial for understanding viral pathogenesis as well as for preventing and treating DNA virus-associated diseases. This review focuses on the current state of our knowledge on how human DNA viruses are sensed by the host innate immune system and how viral proteins counteract this immune response.
Topics: DNA Virus Infections; DNA Viruses; Host-Pathogen Interactions; Humans; Immune Evasion; Immunity, Innate
PubMed: 30265633
DOI: 10.1146/annurev-virology-092917-043244 -
Viruses Mar 2022DNA virus infections are often lifelong and can cause serious diseases in their hosts. Their recognition by the sensors of the innate immune system represents the front... (Review)
Review
DNA virus infections are often lifelong and can cause serious diseases in their hosts. Their recognition by the sensors of the innate immune system represents the front line of host defence. Understanding the molecular mechanisms of innate immunity responses is an important prerequisite for the design of effective antivirotics. This review focuses on the present state of knowledge surrounding the mechanisms of viral DNA genome sensing and the main induced pathways of innate immunity responses. The studies that have been performed to date indicate that herpesviruses, adenoviruses, and polyomaviruses are sensed by various DNA sensors. In non-immune cells, STING pathways have been shown to be activated by cGAS, IFI16, DDX41, or DNA-PK. The activation of TLR9 has mainly been described in pDCs and in other immune cells. Importantly, studies on herpesviruses have unveiled novel participants (BRCA1, H2B, or DNA-PK) in the IFI16 sensing pathway. Polyomavirus studies have revealed that, in addition to viral DNA, micronuclei are released into the cytosol due to genotoxic stress. Papillomaviruses, HBV, and HIV have been shown to evade DNA sensing by sophisticated intracellular trafficking, unique cell tropism, and viral or cellular protein actions that prevent or block DNA sensing. Further research is required to fully understand the interplay between viruses and DNA sensors.
Topics: DNA Virus Infections; DNA, Viral; Herpesviridae; Humans; Immunity, Innate; Polyomavirus
PubMed: 35458396
DOI: 10.3390/v14040666 -
Journal of Molecular Evolution Jan 2020Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire... (Review)
Review
Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life. It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus. The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants. In this literature review we try to give a short insight into some general consequences or traits of virus-host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses.
Topics: Adaptation, Physiological; Animals; Biological Evolution; DNA Viruses; Evolution, Molecular; Host Microbial Interactions; Humans; Viruses
PubMed: 31599342
DOI: 10.1007/s00239-019-09913-4 -
Viruses Nov 2023Oncolytic viruses (OVs) have emerged as one of the most promising cancer immunotherapy agents that selectively target and kill cancer cells while sparing normal cells.... (Review)
Review
Oncolytic viruses (OVs) have emerged as one of the most promising cancer immunotherapy agents that selectively target and kill cancer cells while sparing normal cells. OVs are from diverse families of viruses and can possess either a DNA or an RNA genome. These viruses also have either a natural or engineered tropism for cancer cells. Oncolytic DNA viruses have the additional advantage of a stable genome and multiple-transgene insertion capability without compromising infection or replication. Herpes simplex virus 1 (HSV-1), a member of the oncolytic DNA viruses, has been approved for the treatment of cancers. This success with HSV-1 was achievable by introducing multiple genetic modifications within the virus to enhance cancer selectivity and reduce the toxicity to healthy cells. Here, we review the natural characteristics of and genetically engineered changes in selected DNA viruses that enhance the tumor tropism of these oncolytic viruses.
Topics: Humans; Oncolytic Virotherapy; Neoplasms; Herpesvirus 1, Human; Oncolytic Viruses; Tropism; DNA Viruses
PubMed: 38005938
DOI: 10.3390/v15112262 -
Virology Oct 2014The family Marseilleviridae encompasses giant viruses that replicate in free-living Acanthamoeba amoebae. Since the discovery of the founding member Marseillevirus in... (Review)
Review
The family Marseilleviridae encompasses giant viruses that replicate in free-living Acanthamoeba amoebae. Since the discovery of the founding member Marseillevirus in 2007, 7 new marseilleviruses have been observed, including 3 from environmental freshwater, one from a dipteran, and two from symptom-free humans. Marseilleviruses have ≈250-nm-large icosahedral capsids and 346-386-kb-long mosaic genomes that encode 444-497 predicted proteins. They share a small set of core genes with Mimivirus and other large and giant DNA viruses that compose a monophyletic group, first described in 2001. Comparative genomics analyses indicate that the family Marseilleviridae currently includes three lineages and a pan-genome composed of ≈600 genes. Antibodies against marseilleviruses and viral DNA have been observed in a significant proportion of asymptomatic individuals and in the blood and lymph nodes of a child with adenitis; these observations suggest that these giant viruses may be blood borne and question if they may be pathogenic in humans.
Topics: Acanthamoeba; Animals; DNA Viruses; DNA, Viral; Fresh Water; Genome, Viral; Genomics; Humans; Insecta; Phylogeny; Virus Replication
PubMed: 25104553
DOI: 10.1016/j.virol.2014.07.014 -
Current Issues in Molecular Biology 2020Polydnaviruses (PDVs) were originally viewed as large DNA viruses that are beneficial symbionts of parasitoid wasps. Two groups of PDVs were also recognized:... (Review)
Review
Polydnaviruses (PDVs) were originally viewed as large DNA viruses that are beneficial symbionts of parasitoid wasps. Two groups of PDVs were also recognized: bracoviruses (BVs), which are associated with wasps in the family Braconidae, and ichnoviruses (IVs), which are associated with wasps in the family Ichneumonidae. Results to date indicate that BVs are endogenous virus elements (EVEs) that evolved from an ancient betanudivirus. IVs are also likely EVEs but are unrelated to BVs. BVs and IVs are very unusual relative to most known EVEs because they retain many viral functions that benefit wasps in parasitizing hosts. However, BVs and IVs cannot be considered beneficial symbionts because all components of their genomes are fixed in wasps. Recent studies indicate that other nudiviruses have endogenized in insects. Each exhibits a different functional fate from BVs but shares certain architectural features. We discuss options for classifying BVs and other endogenized nudiviruses. We also discuss future directions.
Topics: Biological Evolution; DNA Viruses; Genes, Viral; Genome, Viral; Genomics; Phylogeny; Symbiosis; Virus Physiological Phenomena
PubMed: 31167960
DOI: 10.21775/cimb.034.163 -
ACS Chemical Biology Aug 2023The constant and the sudden emergence of zoonotic human and animal viruses is a significant threat to human health, the world economy, and the world food supply. This...
The constant and the sudden emergence of zoonotic human and animal viruses is a significant threat to human health, the world economy, and the world food supply. This has necessitated the development of broad-spectrum therapeutic strategies to combat these emerging pathogens. Mechanisms that are essential for viral replication and propagation have been successfully targeted in the past to develop broad-spectrum therapeutics that can be readily repurposed to combat new zoonotic pathogens. Because of the importance of viral RNA capping enzymes to viral replication and pathogenesis, as well as their presence in both DNA and RNA viruses, these viral proteins have been a long-standing therapeutic target. Here, we use genome sequencing information and yeast-based platforms (YeRC0M) to identify, characterize, and target viral genome-encoded essential RNA capping enzymes from emerging strains of DNA viruses, i.e., Monkeypox virus and African Swine Fever Virus, which are a significant threat to human and domestic animal health. We first identified and biochemically characterized these viral RNA capping enzymes and their necessary protein domains. We observed significant differences in functional protein domains and organization for RNA capping enzymes from emerging DNA viruses in comparison to emerging RNA viruses. We also observed several differences in the biochemical properties of these viral RNA capping enzymes using our phenotypic yeast-based approaches (YeRC0M) as compared to the previous in vitro studies. Further, using directed evolution, we were able to identify inactivation and attenuation mutations in these essential viral RNA capping enzymes; these data could have implications on virus biocontainment as well as live attenuated vaccine development. We also developed methods that would facilitate high-throughput phenotypic screening to identify broad-spectrum inhibitors that selectively target viral RNA capping enzymes over host RNA capping enzymes. As demonstrated here, our approaches to identify, characterize, and target viral genome-encoded essential RNA capping enzymes are highly modular and can be readily adapted for targeting emerging viral pathogens as well as their variants that emerge in the future.
Topics: Animals; Humans; Swine; Saccharomyces cerevisiae; African Swine Fever Virus; Viruses; RNA, Viral; Virus Replication; DNA Viruses
PubMed: 37498174
DOI: 10.1021/acschembio.3c00243 -
Viruses Nov 2017It is increasingly clear that DNA viruses exploit cellular epigenetic processes to control their life cycles during infection. This review will address epigenetic... (Review)
Review
It is increasingly clear that DNA viruses exploit cellular epigenetic processes to control their life cycles during infection. This review will address epigenetic regulation in members of the polyomaviruses, adenoviruses, human papillomaviruses, hepatitis B, and herpes viruses. For each type of virus, what is known about the roles of DNA methylation, histone modifications, nucleosome positioning, and regulatory RNA in epigenetic regulation of the virus infection will be discussed. The mechanisms used by certain viruses to dysregulate the host cell through manipulation of epigenetic processes and the role of cellular cofactors such as BRD4 that are known to be involved in epigenetic regulation of host cell pathways will also be covered. Specifically, this review will focus on the role of epigenetic regulation in maintaining viral episomes through the generation of chromatin, temporally controlling transcription from viral genes during the course of an infection, regulating latency and the switch to a lytic infection, and global dysregulation of cellular function.
Topics: DNA Methylation; DNA Viruses; Epigenesis, Genetic; Gene Expression Regulation, Viral; Herpesvirus 4, Human; Histone Code; Host-Pathogen Interactions; Humans; Nucleosomes; Plasmids; Protein Processing, Post-Translational; Virus Latency; Virus Physiological Phenomena; Viruses
PubMed: 29149060
DOI: 10.3390/v9110346 -
Cell Host & Microbe May 2016Viral latency can be considered a metastable, nonproductive infection state that is capable of subsequent reactivation to repeat the infection cycle. Viral latent... (Review)
Review
Viral latency can be considered a metastable, nonproductive infection state that is capable of subsequent reactivation to repeat the infection cycle. Viral latent infections have numerous associated pathologies, including cancer, birth defects, neuropathy, cardiovascular disease, chronic inflammation, and immunological dysfunctions. The mechanisms controlling the establishment, maintenance, and reactivation from latency are complex and diversified among virus families, species, and strains. Yet, as examined in this review, common properties of latent viral infections can be defined. Eradicating latent virus has become an important but elusive challenge and will require a more complete understanding of the mechanisms controlling these processes.
Topics: Animals; DNA Viruses; Epigenesis, Genetic; Genes, Viral; Herpesvirus 1, Human; Humans; Virus Diseases; Virus Integration; Virus Latency; Virus Physiological Phenomena; Virus Replication
PubMed: 27173930
DOI: 10.1016/j.chom.2016.04.008