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Infection, Genetics and Evolution :... Apr 2020Polyomaviruses (PyVs) are small DNA viruses that infect several species, including mammals, birds and fishes. Their study gained momentum after the report of previously... (Review)
Review
Polyomaviruses (PyVs) are small DNA viruses that infect several species, including mammals, birds and fishes. Their study gained momentum after the report of previously unidentified viral species in the past decade, and especially, since the description of the first polyomavirus clearly oncogenic for humans. The aim of this work was to review the most relevant aspects of the evolution and molecular epidemiology of polyomaviruses, allowing to reveal general evolutionary patterns and to identify some unaddressed issues and future challenges. The main points analysed included: 1) the species and genera assignation criteria; 2) the hypotheses, mechanisms and timescale of the ancient and recent evolutionary history of polyomaviruses; and 3) the molecular epidemiology of human viruses, with special attention to JC, BK and Merkel cell polyomaviruses.
Topics: Animals; Evolution, Molecular; Humans; Phylogeny; Polyomavirus; Polyomavirus Infections; Tumor Virus Infections
PubMed: 31870972
DOI: 10.1016/j.meegid.2019.104150 -
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 -
Annual Review of Entomology Jan 2021Of the approximately 1,200 plant virus species that have been described to date, nearly one-third are single-stranded DNA (ssDNA) viruses, and all are transmitted by... (Review)
Review
Of the approximately 1,200 plant virus species that have been described to date, nearly one-third are single-stranded DNA (ssDNA) viruses, and all are transmitted by insect vectors. However, most studies of vector transmission of plant viruses have focused on RNA viruses. All known plant ssDNA viruses belong to two economically important families, and , and in recent years, there have been increased efforts to understand whether they have evolved similar relationships with their respective insect vectors. This review describes the current understanding of ssDNA virus-vector interactions, including how these viruses cross insect vector cellular barriers, the responses of vectors to virus circulation, the possible existence of viral replication within insect vectors, and the three-way virus-vector-plant interactions. Despite recent breakthroughs in our understanding of these viruses, many aspects of plant ssDNA virus transmission remain elusive. More effort is needed to identify insect proteins that mediate the transmission of plant ssDNA viruses and to understand the complex virus-insect-plant three-way interactions in the field during natural infection.
Topics: Animals; DNA, Single-Stranded; Geminiviridae; Insect Vectors; Insecta; Nanoviridae; Plants
PubMed: 32931313
DOI: 10.1146/annurev-ento-060920-094531 -
Recent Results in Cancer Research.... 2021Human papillomaviruses (HPVs) are small DNA viruses that infect basal epithelial cells and are the causative agents of cervical, anogenital, as well as oral cancers....
Human papillomaviruses (HPVs) are small DNA viruses that infect basal epithelial cells and are the causative agents of cervical, anogenital, as well as oral cancers. High-risk HPVs are responsible for nearly half of all virally induced cancers. Viral replication and amplification are intimately linked to the stratified epithelium differentiation program. The E6 and E7 proteins contribute to the development of cancers in HPV positive individuals by hijacking cellular processes and causing genetic instability. This genetic instability induces a robust DNA damage response and activating both ATM and ATR repair pathways. These pathways are critical for the productive replication of high-risk HPVs, and understanding how they contribute to the viral life cycle can provide important insights into HPV's role in oncogenesis. This review will discuss the role that differentiation and the DNA damage responses play in productive replication of high-risk HPVs as well as in the development of cancer.
Topics: Alphapapillomavirus; DNA Repair; Humans; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus Infections; Virus Replication
PubMed: 33200365
DOI: 10.1007/978-3-030-57362-1_7 -
Journal of Medical Virology Jan 2023Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING)...
Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway has been identified as a DNA-sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studies have identified oncogenes E7 and E1A of the DNA tumor viruses, human papillomavirus 18 (HPV18) and adenovirus, respectively, as inhibitors of the cGAS-STING pathway. However, the function of STING in infected cells and the mechanism by which HPV18 E7 antagonizes STING-induced Interferon beta production remain unknown. We report that HPV18 E7 selectively antagonizes STING-triggered nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation but not IRF3 activation. HPV18 E7 binds to STING in a region critical for NF-κB activation and blocks the nuclear accumulation of p65. Moreover, E7 inhibition of STING-triggered NF-κB activation is related to HPV pathogenicity but not E7-Rb binding. HPV18 E7, severe acute respiratory syndrome coronavirus-2 open reading frame 3a, human immunodeficiency virus-2 viral protein X, and Kaposi's sarcoma-associated herpesvirus KSHV viral interferon regulatory factor 1 selectively inhibited STING-triggered NF-κB or IRF3 activation, suggesting a convergent evolution among these viruses toward antagonizing host innate immunity. Collectively, selective suppression of the cGAS-STING pathway by viral proteins is likely to be a key pathogenic determinant, making it a promising target for treating oncogenic virus-induced tumor diseases.
Topics: Humans; NF-kappa B; Interferon-beta; Human papillomavirus 18; Nucleotidyltransferases; COVID-19; Immunity, Innate; DNA; DNA Viruses; Oncogene Proteins
PubMed: 36377393
DOI: 10.1002/jmv.28310 -
International Journal of Molecular... Apr 2021Viral infections cause a host of fatal diseases and seriously affect every form of life from bacteria to humans. Although most viral infections can receive appropriate... (Review)
Review
Viral infections cause a host of fatal diseases and seriously affect every form of life from bacteria to humans. Although most viral infections can receive appropriate treatment thereby limiting damage to life and livelihood with modern medicine and early diagnosis, new types of viral infections are continuously emerging that need to be properly and timely treated. As time is the most important factor in the progress of many deadly viral diseases, early detection becomes of paramount importance for effective treatment. Aptamers are small oligonucleotide molecules made by the systematic evolution of ligands by exponential enrichment (SELEX). Aptamers are characterized by being able to specifically bind to a target, much like antibodies. However, unlike antibodies, aptamers are easily synthesized, modified, and are able to target a wider range of substances, including proteins and carbohydrates. With these advantages in mind, many studies on aptamer-based viral diagnosis and treatments are currently in progress. The use of aptamers for viral diagnosis requires a system that recognizes the binding of viral molecules to aptamers in samples of blood, serum, plasma, or in virus-infected cells. From a therapeutic perspective, aptamers target viral particles or host cell receptors to prevent the interaction between the virus and host cells or target intracellular viral proteins to interrupt the life cycle of the virus within infected cells. In this paper, we review recent attempts to use aptamers for the diagnosis and treatment of various viral infections.
Topics: Animals; Antiviral Agents; Aptamers, Nucleotide; DNA Viruses; Humans; RNA Viruses; Viral Proteins; Virion; Virus Diseases
PubMed: 33920628
DOI: 10.3390/ijms22084168 -
Frontiers in Immunology 2020IFI16, hnRNPA2B1, and nuclear cGAS are nuclear-located DNA sensors that play important roles in initiating host antiviral immunity and modulating tumorigenesis. IFI16... (Review)
Review
IFI16, hnRNPA2B1, and nuclear cGAS are nuclear-located DNA sensors that play important roles in initiating host antiviral immunity and modulating tumorigenesis. IFI16 triggers innate antiviral immunity, inflammasome, and suppresses tumorigenesis by recognizing double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), damaged nuclear DNA, or cooperatively interacting with multiple tumor suppressors such as p53 and BRCA1. hnRNPA2B1 initiates interferon (IFN)-α/β production and enhances STING-dependent cytosolic antiviral signaling by directly binding viral dsDNA from invaded viruses and facilitating -methyladenosine (mA) modification of cGAS, IFI16, and STING mRNAs. Nuclear cGAS is recruited to double-stranded breaks (DSBs), suppresses DNA repair, and promotes tumorigenesis. This review briefly describes the nuclear functions of IFI16, hnRNPA2B1, and cGAS, and summarizes the transcriptional, post-transcriptional, and post-translational regulation of these nuclear DNA sensors.
Topics: Cell Transformation, Viral; DNA Virus Infections; DNA Viruses; DNA, Viral; Heterogeneous-Nuclear Ribonucleoprotein Group A-B; Humans; Interferon-alpha; Interferon-beta; Nuclear Proteins; Nucleotidyltransferases; Phosphoproteins; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases
PubMed: 33505405
DOI: 10.3389/fimmu.2020.624556 -
Annual Review of Virology Sep 2019Persistent viral infections require a host cell reservoir that maintains functional copies of the viral genome. To this end, several DNA viruses maintain their genomes... (Review)
Review
Persistent viral infections require a host cell reservoir that maintains functional copies of the viral genome. To this end, several DNA viruses maintain their genomes as extrachromosomal DNA minichromosomes in actively dividing cells. These viruses typically encode a viral protein that binds specifically to viral DNA genomes and tethers them to host mitotic chromosomes, thus enabling the viral genomes to hitchhike or piggyback into daughter cells. Viruses that use this tethering mechanism include papillomaviruses and the gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. This review describes the advantages and consequences of persistent extrachromosomal viral genome replication.
Topics: Chromosomes; DNA Replication; DNA Viruses; DNA, Viral; Genome, Viral; Herpesvirus 4, Human; Herpesvirus 8, Human; Host Microbial Interactions; Humans; Papillomaviridae; Virus Replication
PubMed: 31283444
DOI: 10.1146/annurev-virology-092818-015716 -
Nature Reviews. Microbiology Oct 2020Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas... (Review)
Review
Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. However, viruses have evolved countermeasures that prevent the epigenetic silencing of their genes during lytic replication, and they can also take advantage of epigenetic silencing to establish latent infections. By contrast, the various covalent modifications added to RNAs, termed epitranscriptomic modifications, can positively regulate mRNA translation and/or stability, and both DNA and RNA viruses have evolved to utilize epitranscriptomic modifications as a means to maximize viral gene expression. As a consequence, both chromatin and RNA modifications could serve as novel targets for the development of antivirals. In this Review, we discuss how host epigenetic and epitranscriptomic processes regulate viral gene expression at the levels of chromatin and RNA function, respectively, and explore how viruses modify, avoid or utilize these processes in order to regulate viral gene expression.
Topics: Animals; Antiviral Agents; Chromatin; DNA Viruses; Epigenesis, Genetic; Eukaryotic Cells; Gene Expression Regulation, Viral; Histones; Host-Pathogen Interactions; Humans; Promoter Regions, Genetic; Protein Biosynthesis; RNA Processing, Post-Transcriptional; RNA Viruses; Transcriptome; Virus Latency; Virus Replication
PubMed: 32533130
DOI: 10.1038/s41579-020-0382-3 -
Annual Review of Virology Sep 2020Multipartite virus genomes are composed of several segments, each packaged in a distinct viral particle. Although this puzzling genome architecture is found in ∼17% of... (Review)
Review
Multipartite virus genomes are composed of several segments, each packaged in a distinct viral particle. Although this puzzling genome architecture is found in ∼17% of known viral species, its distribution among hosts or among distinct types of genome-composing nucleic acid remains poorly understood. No convincing advantage of multipartitism has been identified, yet the maintenance of genomic integrity appears problematic. Here we review recent studies shedding light on these issues. Multipartite viruses rapidly modify the copy number of each segment/gene from one host species to another, a putative benefit if host switches are common. One multipartite virus functions in a multicellular way: The segments do not all need to be present in the same cell and can functionally complement across cells, maintaining genome integrity within hosts. The genomic integrity maintenance during host-to-host transmission needs further elucidation. These features challenge several virology foundations and could apply to other multicomponent viral systems.
Topics: DNA Viruses; Genome, Viral; Humans; Virion; Virus Replication; Viruses
PubMed: 32991271
DOI: 10.1146/annurev-virology-010220-063346