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Frontiers in Immunology 2021
Topics: Animals; DNA Virus Infections; DNA Viruses; DNA, Viral; Humans; Immunity, Innate
PubMed: 34276645
DOI: 10.3389/fimmu.2021.644310 -
Nature Communications Oct 2017Many double-stranded DNA viruses, such as Epstein-Barr virus, can establish persistent infection, but the underlying virus-host interactions remain poorly understood....
Many double-stranded DNA viruses, such as Epstein-Barr virus, can establish persistent infection, but the underlying virus-host interactions remain poorly understood. Here we report that in human airway epithelial cells Epstein-Barr virus induces TRIM29, a member of the TRIM family of proteins, to inhibit innate immune activation. Knockdown of TRIM29 in airway epithelial cells enhances type I interferon production, and in human nasopharyngeal carcinoma cells results in almost complete Epstein-Barr virus clearance. TRIM29 is also highly induced by cytosolic double-stranded DNA in myeloid dendritic cells. TRIM29 mice have lower adenovirus titers in the lung, and are resistant to lethal herpes simplex virus-1 infection due to enhanced production of type I interferon. Mechanistically, TRIM29 induces K48-linked ubiquitination of Stimulator of interferon genes, a key adaptor in double-stranded DNA-sensing pathway, followed by its rapid degradation. These data demonstrate that Epstein-Barr virus and possible other double-stranded DNA viruses use TRIM29 to suppress local innate immunity, leading to the persistence of DNA virus infections.Proteins of the TRIM family have regulatory functions in immune signaling, often via ubiquitination of target proteins. Here, the authors show that TRIM29 is induced upon infection with DNA viruses, resulting in degradation of STING, decreased interferon signaling and increased pathogenicity in mice.
Topics: Animals; Cell Line; DNA Virus Infections; DNA Viruses; DNA-Binding Proteins; Dendritic Cells; Epstein-Barr Virus Infections; Gene Silencing; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Immunity, Innate; Interferon Type I; Mice, Knockout; Respiratory Mucosa; Transcription Factors
PubMed: 29038422
DOI: 10.1038/s41467-017-00101-w -
Virology Journal May 2023Promyelocytic leukemia nuclear bodies (PM NBs), often referred to as membraneless organelles, are dynamic macromolecular protein complexes composed of a PML protein core... (Review)
Review
Promyelocytic leukemia nuclear bodies (PM NBs), often referred to as membraneless organelles, are dynamic macromolecular protein complexes composed of a PML protein core and other transient or permanent components. PML NBs have been shown to play a role in a wide variety of cellular processes. This review describes in detail the diverse and complex interactions between small and medium size DNA viruses and PML NBs that have been described to date. The PML NB components that interact with small and medium size DNA viruses include PML protein isoforms, ATRX/Daxx, Sp100, Sp110, HP1, and p53, among others. Interaction between viruses and components of these NBs can result in different outcomes, such as influencing viral genome expression and/or replication or impacting IFN-mediated or apoptotic cell responses to viral infection. We discuss how PML NB components abrogate the ability of adenoviruses or Hepatitis B virus to transcribe and/or replicate their genomes and how papillomaviruses use PML NBs and their components to promote their propagation. Interactions between polyomaviruses and PML NBs that are poorly understood but nevertheless suggest that the NBs can serve as scaffolds for viral replication or assembly are also presented. Furthermore, complex interactions between the HBx protein of hepadnaviruses and several PML NBs-associated proteins are also described. Finally, current but scarce information regarding the interactions of VP3/apoptin of the avian anellovirus with PML NBs is provided. Despite the considerable number of studies that have investigated the functions of the PML NBs in the context of viral infection, gaps in our understanding of the fine interactions between viruses and the very dynamic PML NBs remain. The complexity of the bodies is undoubtedly a great challenge that needs to be further addressed.
Topics: Adenoviridae; Nuclear Proteins; Promyelocytic Leukemia Nuclear Bodies; Promyelocytic Leukemia Protein; Transcription Factors; Viruses; DNA Viruses
PubMed: 37127643
DOI: 10.1186/s12985-023-02049-4 -
Microbiology and Molecular Biology... Jun 2023Immune recognition of viral genome-derived double-stranded RNA (dsRNA) molecules and their subsequent processing into small interfering RNAs (siRNAs) in plants,... (Review)
Review
Immune recognition of viral genome-derived double-stranded RNA (dsRNA) molecules and their subsequent processing into small interfering RNAs (siRNAs) in plants, invertebrates, and mammals trigger specific antiviral immunity known as antiviral RNA interference (RNAi). Immune sensing of viral dsRNA is sequence-independent, and most regions of viral RNAs are targeted by virus-derived siRNAs which extensively overlap in sequence. Thus, the high mutation rates of viruses do not drive immune escape from antiviral RNAi, in contrast to other mechanisms involving specific virus recognition by host immune proteins such as antibodies and resistance (R) proteins in mammals and plants, respectively. Instead, viruses actively suppress antiviral RNAi at various key steps with a group of proteins known as viral suppressors of RNAi (VSRs). Some VSRs are so effective in virus counter-defense that potent inhibition of virus infection by antiviral RNAi is undetectable unless the cognate VSR is rendered nonexpressing or nonfunctional. Since viral proteins are often multifunctional, resistance phenotypes of antiviral RNAi are accurately defined by those infection defects of VSR-deletion mutant viruses that are efficiently rescued by host deficiency in antiviral RNAi. Here, we review and discuss infection defects of VSR-deficient RNA and DNA viruses resulting from the actions of host antiviral RNAi in model systems.
Topics: Animals; RNA Interference; Antiviral Agents; RNA, Small Interfering; RNA, Viral; DNA Viruses; RNA Viruses; Mammals
PubMed: 37052496
DOI: 10.1128/mmbr.00035-22 -
Virus Research May 2019En Bloc transmission of viruses allow multiple genomes to collectivelly penetrate and initiate infection in the same cell, often resulting in enhanced infectivity. Given... (Review)
Review
En Bloc transmission of viruses allow multiple genomes to collectivelly penetrate and initiate infection in the same cell, often resulting in enhanced infectivity. Given the quasispecies (mutant cloud) nature of RNA viruses and many DNA viruses, en bloc transmission of multiple genomes provides different starting points in sequence space to initiate adaptive walks, and has implications for modulation of viral fitness and for the response of viral populations to lethal mutagenesis. Mechanisms that can enable multiple viral genomes to be transported en bloc among hosts has only recently been gaining attention. A growing body of research suggests that extracellular vesicles (EV) are highly prevalent and robust vehicles for en bloc delivery of viral particles and naked infectious genomes among organisms. Both RNA and DNA viruses appear to exploit these vesicles to increase their multiplicity of infection and enhance virulence.
Topics: Animals; DNA Viruses; Extracellular Vesicles; Genome, Viral; Humans; Membrane Lipids; Mice; Quasispecies; RNA Viruses; Virion; Virus Diseases; Virus Replication; Viruses
PubMed: 30928427
DOI: 10.1016/j.virusres.2019.03.023 -
Viruses Jan 2023Scientific progress in understanding, preventing, treating, and managing viral infections and associated diseases exemplifies the extent to which research on small DNA...
Scientific progress in understanding, preventing, treating, and managing viral infections and associated diseases exemplifies the extent to which research on small DNA tumor viruses has impacted human health [...].
Topics: Humans; DNA Viruses; Virus Diseases; DNA Tumor Viruses
PubMed: 36680299
DOI: 10.3390/v15010259 -
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 -
Frontiers in Cellular and Infection... 2022
Topics: Humans; Neoplasms; DNA Viruses
PubMed: 36569205
DOI: 10.3389/fcimb.2022.1103505 -
International Journal of Molecular... May 2018Virus infected host cells serve as a central immune ecological niche during viral infection and replication and stimulate the host immune response via molecular... (Review)
Review
Virus infected host cells serve as a central immune ecological niche during viral infection and replication and stimulate the host immune response via molecular signaling. The viral infection and multiplication process involves complex intracellular molecular interactions between viral components and the host factors. Various types of host cells are also involved to modulate immune factors in delicate and dynamic equilibrium to maintain a balanced immune ecosystem in an infected host tissue. Antiviral host arsenals are equipped to combat or eliminate viral invasion. However, viruses have evolved with strategies to counter against antiviral immunity or hijack cellular machinery to survive inside host tissue for their multiplication. However, host immune systems have also evolved to neutralize the infection; which, in turn, either clears the virus from the infected host or causes immune-mediated host tissue injury. A complex relationship between viral pathogenesis and host antiviral defense could define the immune ecosystem of virus-infected host tissues. Understanding of the molecular mechanism underlying this ecosystem would uncover strategies to modulate host immune function for antiviral therapeutics. This review presents past and present updates of immune-ecological components of virus infected host tissue and explains how viruses subvert the host immune surveillances.
Topics: Antiviral Agents; DNA Viruses; Host-Pathogen Interactions; Humans; Immunity, Innate; Virus Diseases; Virus Replication; Viruses
PubMed: 29734779
DOI: 10.3390/ijms19051379 -
Virologica Sinica Apr 2019RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by... (Review)
Review
RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules (SG) and GW182/DCP-specific RNA processing bodies (PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude mRNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. Virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.
Topics: Animals; Cytoplasmic Granules; DNA Viruses; Gene Expression Regulation; Host Microbial Interactions; Humans; Immunity, Innate; Mice; RNA; RNA Viruses; RNA, Messenger; RNA, Viral; Virus Replication
PubMed: 31037644
DOI: 10.1007/s12250-019-00122-3