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Viruses Mar 2021The SAM and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphohydrolase that plays a crucial role for a variety of different cellular functions. Besides... (Review)
Review
The SAM and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphohydrolase that plays a crucial role for a variety of different cellular functions. Besides balancing intracellular dNTP concentrations, facilitating DNA damage repair, and dampening excessive immune responses, SAMHD1 has been shown to act as a major restriction factor against various virus species. In addition to its well-described activity against retroviruses such as HIV-1, SAMHD1 has been identified to reduce the infectivity of different DNA viruses such as the herpesviruses CMV and EBV, the poxvirus VACV, or the hepadnavirus HBV. While some viruses are efficiently restricted by SAMHD1, others have developed evasion mechanisms that antagonize the antiviral activity of SAMHD1. Within this review, we summarize the different cellular functions of SAMHD1 and highlight the countermeasures viruses have evolved to neutralize the restriction factor SAMHD1.
Topics: DNA Virus Infections; DNA Viruses; Host-Pathogen Interactions; Humans; Retroviridae; Retroviridae Infections; SAM Domain and HD Domain-Containing Protein 1; Viral Interference
PubMed: 33801276
DOI: 10.3390/v13030395 -
Current Issues in Molecular Biology 2021Double-stranded (ds) DNA viruses of the family , commonly known as virophages, are a fascinating group of eukaryotic viruses that depend on a coinfecting giant dsDNA... (Review)
Review
Double-stranded (ds) DNA viruses of the family , commonly known as virophages, are a fascinating group of eukaryotic viruses that depend on a coinfecting giant dsDNA virus of the for their propagation. Instead of replicating in the nucleus, virophages multiply in the cytoplasmic virion factory of a coinfecting giant virus inside a phototrophic or heterotrophic protistal host cell. Virophages are parasites of giant viruses and can inhibit their replication, which may lead to increased survival rates of the infected host cell population. The genomes of virophages are 17-33 kilobase pairs (kbp) long and encode 16-34 proteins. Genetic signatures of virophages can be found in metagenomic datasets from various saltwater and freshwater environments around the planet. Most virophages share a set of conserved genes that code for a major and a minor capsid protein, a cysteine protease, a genome-packaging ATPase, and a superfamily 3 helicase, although the genomes are otherwise diverse and variable. Lavidaviruses share genes with other mobile genetic elements, suggesting that horizontal gene transfer and recombination have been major forces in shaping these viral genomes. Integrases are occasionally found in virophage genomes and enable these DNA viruses to persist as provirophages in the chromosomes of their viral and cellular hosts. As we watch the genetic diversity of this new viral family unfold through metagenomics, additional isolates are still lacking and critical questions regarding their infection cycle, host range, and ecology remain to be answered.
Topics: Capsid; Coinfection; DNA, Viral; Evolution, Molecular; Gene Transfer, Horizontal; Genetic Variation; Genome, Viral; Giant Viruses; Host Microbial Interactions; Host Specificity; Metagenome; Metagenomics; Phylogeny; Virophages; Virus Replication
PubMed: 32089519
DOI: 10.21775/cimb.040.001 -
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 -
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 -
Virologica Sinica Aug 2021Type III interferons (IFNs) represent the most recently discovered group of IFNs. Together with type I IFNs (e.g. IFN-α/β), type III IFNs (IFN-λ) are produced as part... (Review)
Review
Type III interferons (IFNs) represent the most recently discovered group of IFNs. Together with type I IFNs (e.g. IFN-α/β), type III IFNs (IFN-λ) are produced as part of the innate immune response to virus infection, and elicit an anti-viral state by inducing expression of interferon stimulated genes (ISGs). It was initially thought that type I IFNs and type III IFNs perform largely redundant functions. However, it has become evident that type III IFNs particularly play a major role in antiviral protection of mucosal epithelial barriers, thereby serving an important role in the first-line defense against virus infection and invasion at contact areas with the outside world, versus the generally more broad, potent and systemic antiviral effects of type I IFNs. Herpesviruseses are large DNA viruses, which enter their host via mucosal surfaces and establish lifelong, latent infections. Despite the importance of mucosal epithelial cells in the pathogenesis of herpesviruses, our current knowledge on the interaction of herpesviruses with type III IFN is limited and largely restricted to studies on the alphaherpesvirus herpes simplex virus (HSV). This review summarizes the current understanding about the role of IFN-λ in the immune response against herpesvirus infections.
Topics: Antiviral Agents; Herpesviridae; Interferon Type I; Interferons; Simplexvirus; Interferon Lambda
PubMed: 33400088
DOI: 10.1007/s12250-020-00330-2 -
Annual Review of Virology Sep 2021In nature, insects face a constant threat of infection by numerous exogeneous viruses, and their intestinal tracts are the predominant ports of entry. Insects can... (Review)
Review
In nature, insects face a constant threat of infection by numerous exogeneous viruses, and their intestinal tracts are the predominant ports of entry. Insects can acquire these viruses orally during either blood feeding by hematophagous insects or sap sucking and foliage feeding by insect herbivores. However, the insect intestinal tract forms several physical and immunological barriers to defend against viral invasion, including cell intrinsic antiviral immunity, the peritrophic matrix and the mucin layer, and local symbiotic microorganisms. Whether an infection can be successfully established in the intestinal tract depends on the complex interactions between viruses and those barriers. In this review, we summarize recent progress on virus-intestinal tract interplay in insects, in which various underlying mechanisms derived from nutritional status, dynamics of symbiotic microorganisms, and virus-encoded components play intricate roles in the regulation of virus invasion in the intestinal tract, either directly or indirectly.
Topics: Animals; DNA Viruses; Insecta; Intestines
PubMed: 33872516
DOI: 10.1146/annurev-virology-091919-100543 -
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 -
JAMA Network Open Feb 2024Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with...
IMPORTANCE
Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis.
OBJECTIVE
To assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG antibodies to CMV, EBV, HSV-1, or HHV-6. A total of 401 patients younger than 18 years with severe sepsis were enrolled from 9 pediatric intensive care units (PICUs) in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Data were collected from 2015 to 2018. Samples were assayed from 2019 to 2022. Data were analyzed from 2022 to 2023.
MAIN OUTCOMES AND MEASURES
Death while in the PICU.
RESULTS
Among the 401 patients included in the analysis, the median age was 6 (IQR, 1-12) years, and 222 (55.4%) were male. One hundred fifty-four patients (38.4%) were previously healthy, 108 (26.9%) were immunocompromised, and 225 (56.1%) had documented infection(s) at enrollment. Forty-four patients (11.0%) died in the PICU. Viral DNAemia with at least 1 virus (excluding TTV) was detected in 191 patients (47.6%) overall, 63 of 108 patients (58.3%) who were immunocompromised, and 128 of 293 (43.7%) who were not immunocompromised at sepsis onset. After adjustment for age, Pediatric Risk of Mortality score, previously healthy status, and immunocompromised status at sepsis onset, CMV (adjusted odds ratio [AOR], 3.01 [95% CI, 1.36-6.45]; P = .007), HAdV (AOR, 3.50 [95% CI, 1.46-8.09]; P = .006), BKPyV (AOR. 3.02 [95% CI, 1.17-7.34]; P = .02), and HHV-6 (AOR, 2.62 [95% CI, 1.31-5.20]; P = .007) DNAemia were each associated with increased mortality. Two or more viruses were detected in 78 patients (19.5%), with mortality among 12 of 32 (37.5%) who were immunocompromised and 9 of 46 (19.6%) who were not immunocompromised at sepsis onset. Herpesvirus seropositivity was common (HSV-1, 82 of 246 [33.3%]; CMV, 107 of 254 [42.1%]; EBV, 152 of 251 [60.6%]; HHV-6, 253 if 257 [98.4%]). After additional adjustment for receipt of blood products in the PICU, EBV seropositivity was associated with increased mortality (AOR, 6.10 [95% CI, 1.00-118.61]; P = .049).
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that DNAemia for CMV, HAdV, BKPyV, and HHV-6 and EBV seropositivity were independently associated with increased sepsis mortality. Further investigation of the underlying biology of these viral DNA infections in children with sepsis is warranted to determine whether they only reflect mortality risk or contribute to mortality.
Topics: Adolescent; Humans; Male; Child; Infant; Child, Preschool; Female; DNA, Viral; Cohort Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; DNA Viruses; Sepsis; Herpesvirus 1, Human; Cytomegalovirus Infections
PubMed: 38407904
DOI: 10.1001/jamanetworkopen.2024.0383 -
Tumour Virus Research Dec 2023Approximately 20 % of human cancers are associated with virus infection. DNA tumor viruses can induce tumor formation in host cells by disrupting the cell's DNA... (Review)
Review
Approximately 20 % of human cancers are associated with virus infection. DNA tumor viruses can induce tumor formation in host cells by disrupting the cell's DNA replication and repair mechanisms. Specifically, these viruses interfere with the host cell's DNA damage response (DDR), which is a complex network of signaling pathways that is essential for maintaining the integrity of the genome. DNA tumor viruses can disrupt these pathways by expressing oncoproteins that mimic or inhibit various DDR components, thereby promoting genomic instability and tumorigenesis. Recent studies have highlighted the molecular mechanisms by which DNA tumor viruses interact with DDR components, as well as the ways in which these interactions contribute to viral replication and tumorigenesis. Understanding the interplay between DNA tumor viruses and the DDR pathway is critical for developing effective strategies to prevent and treat virally associated cancers. In this review, we discuss the current state of knowledge regarding the mechanisms by which human papillomavirus (HPV), merkel cell polyomavirus (MCPyV), Kaposi's sarcoma-associated herpesvirus (KSHV), and Epstein-Barr virus (EBV) interfere with DDR pathways to facilitate their respective life cycles, and the consequences of such interference on genomic stability and cancer development.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; DNA Tumor Viruses; Neoplasms; Herpesvirus 8, Human; DNA Repair; Carcinogenesis
PubMed: 37918513
DOI: 10.1016/j.tvr.2023.200272