scholarly journals Induction and suppression of NF-kB signalling by a DNA virus of Drosophila

2018 ◽  
Author(s):  
William H. Palmer ◽  
Joep Joosten ◽  
Gijs J. Overheul ◽  
Pascal W. Jansen ◽  
Michiel Vermeulen ◽  
...  
Keyword(s):  
Immune System ◽  
Rna Interference ◽  
Virus Infection ◽  
Immune Responses ◽  
Potent Inhibitor ◽  
Dna Virus ◽  
Dna Viruses ◽  
Antiviral Responses ◽  
Transcription Factor Regulation ◽  
Virus Isolates

AbstractInteractions between the insect immune system and RNA viruses have been best studied in Drosophila, where RNA interference, NF-kB and JAK-STAT pathways underlie antiviral immunity. In response to these immune mechanisms, insect viruses have convergently evolved suppressors of RNA interference that act by diverse mechanisms to permit viral replication. However, interactions between the insect immune system and DNA viruses have received less attention, primarily because few Drosophila-infecting DNA virus isolates are available. Here, we use a recently-isolated DNA virus of Drosophila melanogaster, Kallithea virus, to probe known antiviral immune responses and virus evasion tactics in the context of DNA virus infection. We find that fly mutants for RNA interference and Immune deficiency (Imd), but not Toll, pathways are more susceptible to Kallithea virus infection. We identify the Kallithea virus-encoded protein gp83 as a potent inhibitor of Toll signalling, strongly suggesting that Toll mediates antiviral responses during Kallithea virus infection, but that it is suppressed by the virus. Further, we find that Kallithea gp83 inhibits Toll signalling either through NF-kB transcription factor regulation, or transcriptionally. Together, these results provide a broad description of known antiviral pathways in the context of DNA virus infection and identify the first Toll pathway inhibitor in a Drosophila virus, extending the known diversity of insect virus-encoded immune inhibitors.

scholarly journals Induction and Suppression of NF-κB Signalling by a DNA Virus ofDrosophila

2018 ◽  
Vol 93 (3) ◽  
Author(s):  
William H. Palmer ◽  
Joep Joosten ◽  
Gijs J. Overheul ◽  
Pascal W. Jansen ◽  
Michiel Vermeulen ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Immune System ◽  
Rna Interference ◽  
Virus Infection ◽  
Rna Viruses ◽  
Antiviral Immunity ◽  
Toll Pathway ◽  
Dna Virus ◽  
Dna Viruses ◽  
Content Type

ABSTRACTInteractions between the insect immune system and RNA viruses have been extensively studied inDrosophila, in which RNA interference, NF-κB, and JAK-STAT pathways underlie antiviral immunity. In response to RNA interference, insect viruses have convergently evolved suppressors of this pathway that act by diverse mechanisms to permit viral replication. However, interactions between the insect immune system and DNA viruses have received less attention, primarily because fewDrosophila-infecting DNA virus isolates are available. In this study, we used a recently isolated DNA virus ofDrosophila melanogaster, Kallithea virus (KV; familyNudiviridae), to probe known antiviral immune responses and virus evasion tactics in the context of DNA virus infection. We found that fly mutants for RNA interference and immune deficiency (Imd), but not Toll, pathways are more susceptible to Kallithea virus infection. We identified the Kallithea virus-encoded protein gp83 as a potent inhibitor of Toll signalling, suggesting that Toll mediates antiviral defense against Kallithea virus infection but that it is suppressed by the virus. We found that Kallithea virus gp83 inhibits Toll signalling through the regulation of NF-κB transcription factors. Furthermore, we found that gp83 of the closely related Drosophila innubila nudivirus (DiNV) suppressesD. melanogasterToll signalling, suggesting an evolutionarily conserved function of Toll in defense against DNA viruses. Together, these results provide a broad description of known antiviral pathways in the context of DNA virus infection and identify the first Toll pathway inhibitor in aDrosophilavirus, extending the known diversity of insect virus-encoded immune inhibitors.IMPORTANCECoevolution of multicellular organisms and their natural viruses may lead to an intricate relationship in which host survival requires effective immunity and virus survival depends on evasion of such responses. Insect antiviral immunity and reciprocal virus immunosuppression tactics have been well studied inDrosophila melanogaster, primarily during RNA, but not DNA, virus infection. Therefore, we describe interactions between a recently isolatedDrosophilaDNA virus (Kallithea virus [KV]) and immune processes known to control RNA viruses, such as RNA interference (RNAi) and Imd pathways. We found that KV suppresses the Toll pathway and identified gp83 as a KV-encoded protein that underlies this suppression. This immunosuppressive ability is conserved in another nudivirus, suggesting that the Toll pathway has conserved antiviral activity against DNA nudiviruses, which have evolved suppressors in response. Together, these results indicate that DNA viruses induce and suppress NF-κB responses, and they advance the application of KV as a model to study insect immunity.

scholarly journals Isolation of a natural DNA virus of Drosophila melanogaster, and characterisation of host resistance and immune responses

2017 ◽  
Author(s):  
William H. Palmer ◽  
Nathan Medd ◽  
Philippa M. Beard ◽  
Darren J. Obbard
Keyword(s):  
Drosophila Melanogaster ◽  
Virus Infection ◽  
Immune Responses ◽  
Transcriptional Response ◽  
Fruit Fly ◽  
Model Species ◽  
Dna Virus ◽  
Natural Interaction ◽  
Dna Viruses ◽  
Virus Interaction

AbstractDrosophila melanogaster has played a key role in our understanding of invertebrate immunity. However, both functional and evolutionary studies of host-virus interaction in Drosophila have been limited by a dearth of native virus isolates. In particular, despite a long history of virus research, DNA viruses of D. melanogaster have only recently been described, and none have been available for experimental study. Here we report the isolation and comprehensive characterisation of Kallithea virus, a large double-stranded DNA virus, and the first DNA virus to have been reported from wild populations of D. melanogaster. We find that Kallithea virus infection is costly for adult flies, reaching high titres in both sexes and disproportionately reducing survival in males and movement and late fecundity in females. Using the Drosophila Genetic Reference Panel, we quantify host genetic variance for virus-induced mortality and viral titre and identify candidate host genes that may underlie this variation, including Cdc42-interacting protein 4. Using full transcriptome sequencing of infected males and females, we examine the transcriptional response of flies to Kallithea virus infection, and describe differential regulation of virus-responsive genes. This work establishes Kallithea virus as a new tractable model to study the natural interaction between D. melanogaster and DNA viruses, and we hope it will serve as a basis for future studies of immune responses to DNA viruses in insects.Author SummaryThe fruit fly Drosophila melanogaster is a useful model species to study host-virus interaction and innate immunity. However, few natural viruses of Drosophila have been available for experiments, and no natural DNA viruses of Drosophila melanogaster have been available at all. Although infecting flies with viruses from other insects has been useful to uncover general immune mechanisms, viruses that naturally infect wild flies could help us to learn more about the coevolutionary process, and more about the genes that underlie the host-virus interaction. Here we present an isolate of a DNA virus (named Kallithea Virus) that naturally infects the model species Drosophila melanogaster in the wild. We describe the basic biology of infection by this virus, finding that both male and females flies die from infection, but females are more tolerant of infection than males, while laying lay fewer eggs than uninfected females. We quantify genetic variation for virus resistance in the flies, and we use RNA sequencing to see which genes are expressed in male and female flies in response to infection. These results will form the basis for further research to understand how insects defend themselves against infection by DNA viruses, and how DNA viruses can overcome antiviral defence.

scholarly journals Characterization of Human Antiviral Adaptive Immune Responses during Hepatotropic Virus Infection in HLA-Transgenic Human Immune System Mice

2013 ◽  
Vol 191 (4) ◽  
pp. 1753-1764 ◽  
Author(s):  
Eva Billerbeck ◽  
Joshua A. Horwitz ◽  
Rachael N. Labitt ◽  
Bridget M. Donovan ◽  
Kevin Vega ◽  
...  
Keyword(s):  
Immune System ◽  
Virus Infection ◽  
Immune Responses ◽  
Human Immune System ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Human Immune

scholarly journals PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

2021 ◽  
Vol 17 (9) ◽  
pp. e1009940
Author(s):  
Zhenyu Wang ◽  
Jing Chen ◽  
Xingchen Wu ◽  
Dan Ma ◽  
Xiaohua Zhang ◽  
...  
Keyword(s):  
Virus Infection ◽  
Type I Interferon ◽  
Akt Signaling ◽  
Pcv2 Infection ◽  
Regulation Mechanism ◽  
Type I ◽  
Histone Deacetylase 6 ◽  
Dna Virus ◽  
Dna Viruses ◽  
Interferon Induction

Viruses use diverse strategies to impair the antiviral immunity of host in order to promote infection and pathogenesis. Herein, we found that PCV2 infection promotes the infection of DNA viruses through inhibiting IFN-β induction in vivo and in vitro. In the early phase of infection, PCV2 promotes the phosphorylation of cGAS at S278 via activation of PI3K/Akt signaling, which directly silences the catalytic activity of cGAS. Subsequently, phosphorylation of cGAS at S278 can facilitate the K48-linked poly-ubiquitination of cGAS at K389, which can been served as a signal for recognizing by the ubiquitin-binding domain of histone deacetylase 6 (HDAC6), to promote the translocation of K48-ubiquitinated-cGAS from cytosol to autolysosome depending on the deacetylase activity of HDAC6, thereby eventually resulting in a markedly increased cGAS degradation in PCV2 infection-induced autophagic cells relative to Earle’s Balanced Salt Solution (EBSS)-induced autophagic cells (a typical starving autophagy). Importantly, we found that PCV2 Cap and its binding protein gC1qR act as predominant regulators to promote porcine cGAS phosphorylation and HDAC6 activation through mediating PI3K/AKT signaling and PKCδ signaling activation. Based on this finding, gC1qR-binding activity deficient PCV2 mutant (PCV2RmA) indeed show a weakened inhibitory effect on IFN-β induction and a weaker boost effect for other DNA viruses infection compared to wild-type PCV2. Collectively, our findings illuminate a systematic regulation mechanism by which porcine circovirus counteracts the cGAS-STING signaling pathway to inhibit the type I interferon induction and promote DNA virus infection, and identify gC1qR as an important regulator for the immunosuppression induced by PCV2.

scholarly journals The main DNA viruses significantly affecting pig livestock

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Carlos Díaz ◽  
Vladimír Celer ◽  
Ivo Frébort
Keyword(s):  
Immune System ◽  
Pseudorabies Virus ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Host Immune System ◽  
Dna Virus ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
Porcine Circoviruses

AbstractSwine DNA viruses have developed unique mechanisms for evasion of the host immune system, infection and DNA replication, and finally, construction and release of new viral particles. This article reviews four classes of DNA viruses affecting swine: porcine circoviruses, African swine fever virus, porcine parvoviruses, and pseudorabies virus. Porcine circoviruses belonging to the Circoviridae family are small single-stranded DNA viruses causing different diseases in swine including poly-weaning multisystemic wasting syndrome, porcine dermatitis and nephropathy syndrome, and porcine respiratory disease complex. African swine fever virus, the only member of the Asfivirus genus in the Asfarviridae family, is a large double-stranded DNA virus and for its propensity to cause high mortality, it is currently considered the most dangerous virus in the pig industry. Porcine parvoviruses are small single-stranded DNA viruses belonging to the Parvoviridae family that cause reproductive failure in pregnant gilts. Pseudorabies virus, or suid herpesvirus 1, is a large double-stranded DNA virus belonging to the Herpesviridae family and Alphaherpesvirinae subfamily. Recent findings including general as well as genetic classification, virus structure, clinical syndromes and the host immune system responses and vaccine protection are described for all four swine DNA virus classes.

scholarly journals Therapeutic Approaches for COVID-19 Based on the Interferon-mediated Immune Responses

2021 ◽  
Vol 16 ◽  
Author(s):  
Pouria Mosaddeghi ◽  
Farbod Shahabinezhad ◽  
Zahra Dehghani ◽  
Mitra Farahmandnejad ◽  
Mohammad Javad Taghipour ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Genetic Similarity ◽  
The Body ◽  
Therapeutic Approaches ◽  
Host Immune Responses ◽  
Antiviral Responses ◽  
Interferon Induction ◽  
Optimum Approach ◽  
Novel Virus

Background: As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanism of SARS-CoV-2, the causing agent of COVID-19, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV as well as the comparable pattern of age-mortality relations suggest that some previous findings on SARS could be applicable for COVID-19. Objective: The aim of this study was to investigate the most important signaling pathways activated by coronaviruses to better understand the viral pathogenesis and host immune responses. Method: Here, a systems biology study was conducted on a SARS database. It was followed by a literature review on the cognate subject. Results: It was proved that interferons may possess a crucial role in the defense against coronavirus diseases. The literature supported the validity of the employed approach and the notion that interferon induction could play a key role in the body defense against coronavirus infections. Conclusion: Altogether, administration of interferons or interferon-inducing agents in a prophylactic manner or at early stages of the disease, could mimic the effective antiviral responses against SARS-CoV-2 and reduce the disease severity. At later stages of the disease, however, the balance of the immune reactions would be disrupted and the responses would shift toward immunopathogenic over-reactions, which could be exacerbated by interferon usage. Moderating the activity of the immune system by anti-inflammatory agents, might be the optimum approach in such conditions.

scholarly journals Metagenomic profiling of placental tissue suggests DNA virus infection of the placenta is rare

2021 ◽  
Vol 102 (11) ◽  
Author(s):  
Adam A. Witney ◽  
Sean Aller ◽  
Blair L. Strang
Keyword(s):  
Virus Infection ◽  
Dna Sequences ◽  
Placental Tissue ◽  
Viral Transmission ◽  
Dna Virus ◽  
Viral Dna ◽  
Dna Viruses ◽  
Virus Sequence ◽  
Term Births ◽  
Human Herpesviruses

It is widely recognized that pathogens can be transmitted across the placenta from mother to foetus. Recent re-evaluation of metagenomic studies indicates that the placenta has no unique microbiome of commensal bacteria. However, viral transmission across the placenta, including transmission of DNA viruses such as the human herpesviruses, is possible. A fuller understanding of which DNA virus sequence can be found in the placenta is required. We employed a metagenomic analysis to identify viral DNA sequences in placental metagenomes from full-term births (20 births), pre-term births (13 births), births from pregnancies associated with antenatal infections (12 births) or pre-term births with antenatal infections (three births). Our analysis found only a small number of DNA sequences corresponding to the genomes of human herpesviruses in four of the 48 metagenomes analysed. Therefore, our data suggest that DNA virus infection of the placenta is rare and support the concept that the placenta is largely free of pathogen infection.

scholarly journals Host Noncoding Retrotransposons Induced by DNA Viruses: a SINE of Infection?

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Jessica M. Tucker ◽  
Britt A. Glaunsinger
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Virus Infection ◽  
Rna Polymerase ◽  
Reverse Transcription ◽  
Noncoding Rna ◽  
Rna Polymerase Iii ◽  
Dna Virus ◽  
Dna Viruses ◽  
Gene Regulatory

ABSTRACT Our genomes are dominated by repetitive elements. The majority of these elements derive from retrotransposons, which expand throughout the genome through a process of reverse transcription and integration. Short interspersed nuclear elements, or SINEs, are an abundant class of retrotransposons that are transcribed by RNA polymerase III, thus generating exclusively noncoding RNA (ncRNA) that must hijack the machinery required for their transposition. SINE loci are generally transcriptionally repressed in somatic cells but can be robustly induced upon infection with multiple DNA viruses. Recent research has focused on the gene expression and signaling events that are modulated by SINE ncRNAs, particularly during gammaherpesvirus infection. Here, we review the biology of these SINE ncRNAs, explore how DNA virus infection may lead to their induction, and describe how novel gene regulatory and immune-related functions of these ncRNAs may impact the viral life cycle.

scholarly journals Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 182
Author(s):  
Cindy Chiang ◽  
Guanqun Liu ◽  
Michaela U. Gack
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Deubiquitinating Enzymes ◽  
Viral Pathogens ◽  
Dna Viruses ◽  
E3 Ligases ◽  
Antiviral Responses

Viral dysregulation or suppression of innate immune responses is a key determinant of virus-induced pathogenesis. Important sensors for the detection of virus infection are the RIG-I-like receptors (RLRs), which, in turn, are antagonized by many RNA viruses and DNA viruses. Among the different escape strategies are viral mechanisms to dysregulate the post-translational modifications (PTMs) that play pivotal roles in RLR regulation. In this review, we present the current knowledge of immune evasion by viral pathogens that manipulate ubiquitin- or ISG15-dependent mechanisms of RLR activation. Key viral strategies to evade RLR signaling include direct targeting of ubiquitin E3 ligases, active deubiquitination using viral deubiquitinating enzymes (DUBs), and the upregulation of cellular DUBs that regulate RLR signaling. Additionally, we summarize emerging new evidence that shows that enzymes of certain coronaviruses such as SARS-CoV-2, the causative agent of the current COVID-19 pandemic, actively deISGylate key molecules in the RLR pathway to escape type I interferon (IFN)-mediated antiviral responses. Finally, we discuss the possibility of targeting virally-encoded proteins that manipulate ubiquitin- or ISG15-mediated innate immune responses for the development of new antivirals and vaccines.

Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

2020 ◽  
Vol 15 (7) ◽  
pp. 441-453
Author(s):  
Ana Vazquez-Pagan ◽  
Rebekah Honce ◽  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Pregnant Women ◽  
Disease Severity ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Influenza Virus Infection ◽  
Severe Influenza ◽  
The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

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