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Biomolecules Jul 2022Although traditionally viewed as streamlined and simple, discoveries over the last century have revealed that viruses can exhibit surprisingly complex physical... (Review)
Review
Although traditionally viewed as streamlined and simple, discoveries over the last century have revealed that viruses can exhibit surprisingly complex physical structures, genomic organization, ecological interactions, and evolutionary histories. Viruses can have physical dimensions and genome lengths that exceed many cellular lineages, and their infection strategies can involve a remarkable level of physiological remodeling of their host cells. Virus-virus communication and widespread forms of hyperparasitism have been shown to be common in the virosphere, demonstrating that dynamic ecological interactions often shape their success. And the evolutionary histories of viruses are often fraught with complexities, with chimeric genomes including genes derived from numerous distinct sources or evolved de novo. Here we will discuss many aspects of this viral complexity, with particular emphasis on large DNA viruses, and provide an outlook for future research.
Topics: Biological Evolution; DNA Viruses; Genome, Viral; Genomics; Phylogeny; Viruses
PubMed: 36008955
DOI: 10.3390/biom12081061 -
Virology May 2015Virus genomes are condensed and packaged inside stable proteinaceous capsids that serve to protect them during transit from one cell or host organism, to the next.... (Review)
Review
Virus genomes are condensed and packaged inside stable proteinaceous capsids that serve to protect them during transit from one cell or host organism, to the next. During virus entry, capsid shells are primed and disassembled in a complex, tightly-regulated, multi-step process termed uncoating. Here we compare the uncoating-programs of DNA viruses of the pox-, herpes-, adeno-, polyoma-, and papillomavirus families. Highlighting the chemical and mechanical cues virus capsids respond to, we review the conformational changes that occur during stepwise disassembly of virus capsids and how these culminate in the release of viral genomes at the right time and cellular location to assure successful replication.
Topics: Capsid Proteins; DNA Viruses; DNA, Viral; Virus Uncoating
PubMed: 25728300
DOI: 10.1016/j.virol.2015.01.024 -
Journal of Clinical Oncology : Official... Nov 2017Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related...
Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation.
Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related mortality from severe viral infections. Adoptively transferred virus-specific T cells (VSTs) generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available off-the-shelf product. Patient and Methods We generated a bank of VSTs that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). The VSTs were administered to 38 patients with 45 infections in a phase II clinical trial. Results A single infusion produced a cumulative complete or partial response rate of 92% (95% CI, 78.1% to 98.3%) overall and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 100% for EBV (n = 2), and 67% for HHV-6 (n = 3). Clinical benefit was achieved in 31 patients treated for one infection and in seven patients treated for multiple coincident infections. Thirteen of 14 patients treated for BKV-associated hemorrhagic cystitis experienced complete resolution of gross hematuria by week 6. Infusions were safe, and only two occurrences of de novo graft-versus host disease (grade 1) were observed. VST tracking by epitope profiling revealed persistence of functional VSTs of third-party origin for up to 12 weeks. Conclusion The use of banked VSTs is a feasible, safe, and effective approach to treat severe and drug-refractory infections after HSCT, including infections from two viruses (BKV and HHV-6) that had never been targeted previously with an off-the-shelf product. Furthermore, the multispecificity of the VSTs ensures extensive antiviral coverage, which facilitates the treatment of patients with multiple infections.
Topics: Adenoviruses, Human; Adult; BK Virus; DNA Virus Infections; DNA Viruses; Female; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Herpesvirus 6, Human; Humans; Immunotherapy, Adoptive; Male; T-Lymphocytes; Transplantation, Homologous; Treatment Outcome
PubMed: 28783452
DOI: 10.1200/JCO.2017.73.0655 -
Annual Review of Virology Sep 2018Viral DNA genomes have limited coding capacity and therefore harness cellular factors to facilitate replication of their genomes and generate progeny virions. Studies of... (Review)
Review
Viral DNA genomes have limited coding capacity and therefore harness cellular factors to facilitate replication of their genomes and generate progeny virions. Studies of viruses and how they interact with cellular processes have historically provided seminal insights into basic biology and disease mechanisms. The replicative life cycles of many DNA viruses have been shown to engage components of the host DNA damage and repair machinery. Viruses have evolved numerous strategies to navigate the cellular DNA damage response. By hijacking and manipulating cellular replication and repair processes, DNA viruses can selectively harness or abrogate distinct components of the cellular machinery to complete their life cycles. Here, we highlight consequences for viral replication and host genome integrity during the dynamic interactions between virus and host.
Topics: DNA Damage; DNA Repair; DNA Replication; DNA Viruses; DNA, Viral; Virus Replication
PubMed: 29996066
DOI: 10.1146/annurev-virology-092917-043534 -
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 -
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 Virology Feb 2014Viruses employ a variety of strategies to usurp and control cellular activities through the orchestrated recruitment of macromolecules to specific cytoplasmic or nuclear... (Review)
Review
Viruses employ a variety of strategies to usurp and control cellular activities through the orchestrated recruitment of macromolecules to specific cytoplasmic or nuclear compartments. Formation of such specialized virus-induced cellular microenvironments, which have been termed viroplasms, virus factories, or virus replication centers, complexes, or compartments, depends on molecular interactions between viral and cellular factors that participate in viral genome expression and replication and are in some cases associated with sites of virion assembly. These virus-induced compartments function not only to recruit and concentrate factors required for essential steps of the viral replication cycle but also to control the cellular mechanisms of antiviral defense. In this review, we summarize characteristic features of viral replication compartments from different virus families and discuss similarities in the viral and cellular activities that are associated with their assembly and the functions they facilitate for viral replication.
Topics: Animals; Cell Nucleus; Cytoplasm; DNA Viruses; Humans; Virus Diseases; Virus Replication
PubMed: 24257611
DOI: 10.1128/JVI.02046-13 -
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 Apr 2023, so called because of its "mimicking microbe", was discovered in 2003 and was the founding member of the first family of giant viruses isolated from amoeba. These giant... (Review)
Review
, so called because of its "mimicking microbe", was discovered in 2003 and was the founding member of the first family of giant viruses isolated from amoeba. These giant viruses, present in various environments, have opened up a previously unexplored field of virology. Since 2003, many other giant viruses have been isolated, founding new families and taxonomical groups. These include a new giant virus which was isolated in 2015, the result of the first co-culture on . This new giant virus was named "Faustovirus". Its closest known relative at that time was African Swine Fever Virus. Pacmanvirus and Kaumoebavirus were subsequently discovered, exhibiting phylogenetic clustering with the two previous viruses and forming a new group with a putative common ancestor. In this study, we aimed to summarise the main features of the members of this group of giant viruses, including Abalone Asfarvirus, African Swine Fever Virus, Faustovirus, Pacmanvirus, and Kaumoebavirus.
Topics: Swine; Animals; Giant Viruses; Phylogeny; African Swine Fever Virus; Viruses; Mimiviridae; DNA Viruses; Genome, Viral
PubMed: 37112995
DOI: 10.3390/v15041015 -
Viruses Apr 2019Parvoviruses, infecting vertebrates and invertebrates, are a family of single-stranded DNA viruses with small, non-enveloped capsids with T = 1 icosahedral symmetry. A... (Review)
Review
Parvoviruses, infecting vertebrates and invertebrates, are a family of single-stranded DNA viruses with small, non-enveloped capsids with T = 1 icosahedral symmetry. A quarter of a century after the first parvovirus capsid structure was published, approximately 100 additional structures have been analyzed. This first structure was that of Canine Parvovirus, and it initiated the practice of structure-to-function correlation for the family. Despite high diversity in the capsid viral protein (VP) sequence, the structural topologies of all parvoviral capsids are conserved. However, surface loops inserted between the core secondary structure elements vary in conformation that enables the assembly of unique capsid surface morphologies within individual genera. These variations enable each virus to establish host niches by allowing host receptor attachment, specific tissue tropism, and antigenic diversity. This review focuses on the diversity among the parvoviruses with respect to the transcriptional strategy of the encoded VPs, the advances in capsid structure-function annotation, and therapeutic developments facilitated by the available structures.
Topics: Animals; Capsid Proteins; Cryoelectron Microscopy; Crystallography, X-Ray; Humans; Models, Molecular; Parvoviridae Infections; Parvovirus; Protein Conformation; Protein Structure, Secondary
PubMed: 31010002
DOI: 10.3390/v11040362