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 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 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 Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1086
Author(s):  
Francois Helle ◽  
Lynda Handala ◽  
Marine Bentz ◽  
Gilles Duverlie ◽  
Etienne Brochot
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Rna Viruses ◽  
Viral Transmission ◽  
Viral Fitness ◽  
Host Cells ◽  
Dna Viruses ◽  
Recent Advances ◽  
Viral Particles ◽  
Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

scholarly journals Pacmanvirus, a New Giant Icosahedral Virus at the Crossroads between Asfarviridae and Faustoviruses

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Julien Andreani ◽  
Jacques Yaacoub Bou Khalil ◽  
Madhumati Sevvana ◽  
Samia Benamar ◽  
Fabrizio Di Pinto ◽  
...  
Keyword(s):  
African Swine Fever Virus ◽  
Acanthamoeba Castellanii ◽  
Genomic Analysis ◽  
African Swine Fever ◽  
Fever Virus ◽  
Dna Virus ◽  
Dna Viruses ◽  
Content Type ◽  
Double Stranded Dna ◽  
Protein Locus

ABSTRACT African swine fever virus, a double-stranded DNA virus that infects pigs, is the only known member of the Asfarviridae family. Nevertheless, during our isolation and sequencing of the complete genome of faustovirus, followed by the description of kaumoebavirus, carried out over the past 2 years, we observed the emergence of previously unknown related viruses within this group of viruses. Here we describe the isolation of pacmanvirus, a fourth member in this group, which is capable of infecting Acanthamoeba castellanii. Pacmanvirus A23 has a linear compact genome of 395,405 bp, with a 33.62% G+C content. The pacmanvirus genome harbors 465 genes, with a high coding density. An analysis of reciprocal best hits shows that 31 genes are conserved between African swine fever virus, pacmanvirus, faustovirus, and kaumoebavirus. Moreover, the major capsid protein locus of pacmanvirus appears to be different from those of kaumoebavirus and faustovirus. Overall, comparative and genomic analyses reveal the emergence of a new group or cluster of viruses encompassing African swine fever virus, faustovirus, pacmanvirus, and kaumoebavirus. IMPORTANCE Pacmanvirus is a newly discovered icosahedral double-stranded DNA virus that was isolated from an environmental sample by amoeba coculture. We describe herein its structure and replicative cycle, along with genomic analysis and genomic comparisons with previously known viruses. This virus represents the third virus, after faustovirus and kaumoebavirus, that is most closely related to classical representatives of the Asfarviridae family. These results highlight the emergence of previously unknown double-stranded DNA viruses which delineate and extend the diversity of a group around the asfarvirus members.

scholarly journals Human IFIT3 Protein Induces Interferon Signaling and Inhibits Adenovirus Immediate Early Gene Expression

mBio ◽  
2021 ◽  
Author(s):  
Aniska Chikhalya ◽  
Meike Dittmann ◽  
Yueting Zheng ◽  
Sook-Young Sohn ◽  
Charles M. Rice ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Viruses ◽  
Early Gene ◽  
Immediate Early ◽  
Interferon Signaling ◽  
Dna Virus ◽  
Dna Viruses ◽  
Early Gene Expression ◽  
Partner Proteins ◽  
Induced Proteins

IFITs belong to a family of IFN-induced proteins that have broad antiviral functions, primarily studied with RNA viruses leaving a gap of knowledge on the effects of these proteins on DNA viruses. In this study we show that IFIT3, with its partner proteins IFIT1 and IFIT2, specifically restricts replication of human Ad, a DNA virus, by stimulating IFNβ production via the STING and MAVS pathways.

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 Role of DCP1-DCP2 complex regulated by viral and host microRNAs in DNA virus infection

2018 ◽  
Author(s):  
Yuechao Sun ◽  
Xiaobo Zhang
Keyword(s):  
Virus Infection ◽  
White Spot Syndrome Virus ◽  
Antiviral Immunity ◽  
Underlying Mechanism ◽  
Rnai Pathway ◽  
Dna Virus ◽  
Positive Role ◽  
Host Interactions ◽  
Negative Effect

AbstractThe DCP1-DCP2 complex can regulate the animal antiviral immunity by the decapping of retrovirus RNAs and the suppression of RNAi pathway. However, the influence of DCP1-DCP2 complex on DNA virus infection and the regulation of DCP1-DCP2 complex by microRNAs (miRNAs) remain unclear. In this study, we investigated the role of miRNA-regulated DCP1-DCP2 complex in DNA virus infection. Our results suggested that the DCP1-DCP2 complex played a positive role in the infection of white spot syndrome virus (WSSV), a DNA virus of shrimp. The N-terminal regulatory domain of DCP2 was interacted with the EVH1 domain of DCP1, forming the DCP1-DCP2 complex. Furthermore, a host shrimp miRNA (miR-87) inhibited WSSV infection by targeting the host DCP2 gene and a viral miRNA (WSSV-miR-N46) took a negative effect on WSSV replication by targeting the host DCP1 gene. Therefore, our study provided novel insights into the underlying mechanism of DCP1-DCP2 complex and its regulation by miRNAs in virus-host interactions.The DCP1-DCP2 complex can regulate the animal antiviral immunity by the decapping of retrovirus RNAs and the suppression of RNAi pathway. In the present study, the findings indicated that the silencing of the DCP1-DCP2 complex inhibited the infection of WSSV, a DNA virus of shrimp, suggesting that the DCP1-DCP2 complex facilitated DNA virus infection. Due to the suppressive role of the DCP1-DCP2 complex in RNAi pathway against virus infection, the DCP1-DCP2 complex could promote WSSV infection in shrimp. In this context, our study contributed a novel aspect of the DCP1-DCP2 complex in virus-host interactions. Our study revealed that the host and viral miRNAs could regulate the DCP1-DCP2 complex to affect virus infection. Therefore, our study provided novel insights into the miRNA-mediated regulation of DCP1-DCP2 complex took great effects on RNAi immunity of invertebrates against virus infection.

scholarly journals Inhibition of a Large Double-Stranded DNA Virus by MxA Protein

2008 ◽  
Vol 83 (5) ◽  
pp. 2310-2320 ◽  
Author(s):  
Christopher L. Netherton ◽  
Jennifer Simpson ◽  
Otto Haller ◽  
Thomas E. Wileman ◽  
Haru-Hisa Takamatsu ◽  
...  
Keyword(s):  
Rna Viruses ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Vero Cells ◽  
Dna Virus ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
Late Protein ◽  
B Virus ◽  
Negative Sense

ABSTRACT Increasing evidence points to the importance of the interferon (IFN) response in determining the host range and virulence of African swine fever virus (ASFV). Infection with attenuated strains of ASFV leads to the upregulation of genes controlled by IFN pathways, including myxovirus resistance (Mx) genes that are potent effectors of the antiviral state. Mx gene products are known to inhibit the replication of many negative-sense single-stranded RNA viruses, as well as double-stranded RNA viruses, positive-sense single-stranded RNA viruses, and the reverse-transcribing DNA virus hepatitis B virus. Here, we provide data that extend the known range of viruses inhibited by Mx to include the large double-stranded DNA viruses. Stably transfected Vero cells expressing human MxA protein did not support ASFV plaque formation, and virus replication in these cells was reduced 100-fold compared with that in control cells. In contrast, ASFV replication in cells expressing MxB protein or a mutant MxA protein was similar to that in control Vero cells. There was a drastic reduction in ASFV late protein synthesis in MxA-expressing cells, correlating with the results of previous work on the effect of IFN on viral replication. Strikingly, the inhibition of ASFV replication was linked to the recruitment of MxA protein to perinuclear viral assembly sites, where the protein surrounded the virus factories. Interactions between ASFV and MxA were similar to those seen between MxA and different RNA viruses, suggesting a common inhibitory mechanism.

An Overview of Immune Evasion Strategies of DNA and RNA Viruses

2021 ◽  
Vol 21 ◽  
Author(s):  
Sheikh Saba Naz ◽  
Afsheen Aslam ◽  
Taqdees Malik
Keyword(s):  
Immune System ◽  
Rna Viruses ◽  
Adaptor Proteins ◽  
Genomic Diversity ◽  
Host Immune System ◽  
Granule Formation ◽  
Dna Viruses ◽  
Defense Proteins ◽  
Dna And Rna ◽  
Cytokines And Chemokines

A successful viral infection is due to the effective evasion of viruses from the immune system. The entry of viruses is usually detected by different cellular receptors including PRRs. Recognition of the viral genome leads to the production of interferons through a signaling stream. This review article will give brief information about escaping mechanisms of DNA and RNA viruses from the host immune system. Glimpses of these strategies include viral endonuclease activity, cap snatching of host mRNA, the formation of replication organelles, stress granule formation, membrane modifications, action of proteases, and evasion from ISGs. Moreover, we will discuss the strategies of DNA viruses to inhibit immune responses include Subversion of mRNA, transcriptional factors, Adaptor proteins, PRRs, evasion from T lymphocytes, Genomic Diversity, Theft or seize of host defense proteins, Imitation of host factors like affecting cytokines and chemokines of the host, and suppression or inhibition of apoptosis, Proteasomal degradation of host antiviral proteins by DNA Viruses. This knowledge is pivotal in understanding of different methodologies that viruses have created to escape antiviral cellular reactions of the host as well as an understanding of virus-host interactions and the origin of viral pathogenesis. Also, this knowledge is significant for the design of gene targeting vectors, antiviral vaccines, and the development of effective treatments directed against DNA and RNA viruses.

scholarly journals Deletion of Cytoplasmic Double-Stranded RNA Sensors Does Not Uncover Viral Small Interfering RNA Production in Human Cells

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Susan Schuster ◽  
Lotte E. Tholen ◽  
Gijs J. Overheul ◽  
Frank J. M. van Kuppeveld ◽  
Ronald P. van Rij
Keyword(s):  
Rna Interference ◽  
Antiviral Activity ◽  
Mammalian Cells ◽  
Rna Viruses ◽  
Antiviral Immunity ◽  
Antiviral Effect ◽  
Interferon Response ◽  
Rnai Pathway ◽  
Differentiated Cells ◽  
Positive Sense

ABSTRACT The contribution of the RNA interference (RNAi) pathway in antiviral immunity in vertebrates has been widely debated. It has been proposed that RNAi possesses antiviral activity in mammalian systems but that its antiviral effect is masked by the potent antiviral interferon response in differentiated mammalian cells. In this study, we show that inactivation of the interferon response is not sufficient to uncover antiviral activity of RNAi in human epithelial cells infected with three wild-type positive-sense RNA viruses. Antiviral immunity in insects and plants is mediated by the RNA interference (RNAi) pathway in which viral long double-stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs) by Dicer enzymes. Although this pathway is evolutionarily conserved, its involvement in antiviral defense in mammals is the subject of debate. In vertebrates, recognition of viral RNA induces a sophisticated type I interferon (IFN)-based immune response, and it has been proposed that this response masks or inhibits antiviral RNAi. To test this hypothesis, we analyzed viral small RNA production in differentiated cells deficient in the cytoplasmic RNA sensors RIG-I and MDA5. We did not detect 22-nucleotide (nt) viral siRNAs upon infection with three different positive-sense RNA viruses. Our data suggest that the depletion of cytoplasmic RIG-I-like sensors is not sufficient to uncover viral siRNAs in differentiated cells. IMPORTANCE The contribution of the RNA interference (RNAi) pathway in antiviral immunity in vertebrates has been widely debated. It has been proposed that RNAi possesses antiviral activity in mammalian systems but that its antiviral effect is masked by the potent antiviral interferon response in differentiated mammalian cells. In this study, we show that inactivation of the interferon response is not sufficient to uncover antiviral activity of RNAi in human epithelial cells infected with three wild-type positive-sense RNA viruses.

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