scholarly journals Giant DNA Virus Mimivirus Encodes Pathway for Biosynthesis of Unusual Sugar 4-Amino-4,6-dideoxy-d-glucose (Viosamine)

2011 ◽  
Vol 287 (5) ◽  
pp. 3009-3018 ◽  
Author(s):  
Francesco Piacente ◽  
Margherita Marin ◽  
Antonio Molinaro ◽  
Cristina De Castro ◽  
Virginie Seltzer ◽  
...  
Keyword(s):  
Dna Virus

scholarly journals β-Catenin Is Required for the cGAS/STING Signaling Pathway but Antagonized by the Herpes Simplex Virus 1 US3 Protein

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Hongjuan You ◽  
Yingying Lin ◽  
Feng Lin ◽  
Mingyue Yang ◽  
Jiahui Li ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Kinase Activity ◽  
Dna Virus ◽  
Host Immune Responses ◽  
Simplex Virus ◽  
Antiviral Innate Immunity ◽  
Hsv 1

ABSTRACT The cGAS/STING-mediated DNA-sensing signaling pathway is crucial for interferon (IFN) production and host antiviral responses. Herpes simplex virus I (HSV-1) is a DNA virus that has evolved multiple strategies to evade host immune responses. Here, we demonstrate that the highly conserved β-catenin protein in the Wnt signaling pathway is an important factor to enhance the transcription of type I interferon (IFN-I) in the cGAS/STING signaling pathway, and the production of IFN-I mediated by β-catenin was antagonized by HSV-1 US3 protein via its kinase activity. Infection by US3-deficienct HSV-1 and its kinase-dead variants failed to downregulate IFN-I and IFN-stimulated gene (ISG) production induced by β-catenin. Consistent with this, absence of β-catenin enhanced the replication of US3-deficienct HSV-1, but not wild-type HSV-1. The underlying mechanism was the interaction of US3 with β-catenin and its hyperphosphorylation of β-catenin at Thr556 to block its nuclear translocation. For the first time, HSV-1 US3 has been shown to inhibit IFN-I production through hyperphosphorylation of β-catenin and to subvert host antiviral innate immunity. IMPORTANCE Although increasing evidence has demonstrated that HSV-1 subverts host immune responses and establishes lifelong latent infection, the molecular mechanisms by which HSV-1 interrupts antiviral innate immunity, especially the cGAS/STING-mediated cellular DNA-sensing signaling pathway, have not been fully explored. Here, we show that β-catenin promotes cGAS/STING-mediated activation of the IFN pathway, which is important for cellular innate immune responses and intrinsic resistance to DNA virus infection. The protein kinase US3 antagonizes the production of IFN by targeting β-catenin via its kinase activity. The findings in this study reveal a novel mechanism for HSV-1 to evade host antiviral immunity and add new knowledge to help in understanding the interaction between the host and HSV-1 infection.

scholarly journals Circular Double-Stranded Forms of TT Virus DNA in the Liver

2000 ◽  
Vol 74 (11) ◽  
pp. 5161-5167 ◽  
Author(s):  
Hiroaki Okamoto ◽  
Masato Ukita ◽  
Tsutomu Nishizawa ◽  
Junichi Kishimoto ◽  
Yuji Hoshi ◽  
...  
Keyword(s):  
Human Beings ◽  
Specific Primer ◽  
Dna Virus ◽  
S1 Nuclease ◽  
Tt Virus ◽  
Double Stranded Dna ◽  
Replicative Intermediates ◽  
Paired Serum ◽  
Genomic Length ◽  
Liver Tissues

ABSTRACT TT virus (TTV) is an unenveloped, circular, and single-stranded DNA virus commonly infecting human beings worldwide. TTV DNAs in paired serum and liver tissues from three viremic individuals were separated by gel electrophoresis and characterized biophysically. TTV DNAs in sera migrated in sizes ranging from 2.0 to 2.5 kb. TTV DNAs in liver tissues, however, migrated at 2.0 to 2.5 kb as well as at 3.5 to 6.1 kb. Both faster- and slower-migrating forms of TTV DNAs in the liver were found to be circular and of the full genomic length of 3.8 kb. TTV DNAs migrating at 2.0 to 2.5 kb, from either serum or liver tissues, were sensitive to S1 nuclease but resistant to restriction endonucleases, and therefore, they were single-stranded. By contrast, TTV DNAs in liver tissues that migrated at 3.5 to 6.1 kb were resistant to S1 nuclease. They migrated at 3.7 to 4.0 kb after digestion with EcoRI, which suggests that they represent circular, double-stranded replicative intermediates of TTV. When TTV DNAs were subjected to strand-specific primer extension and then amplified by PCR with internal primers, those in serum were found to be minus-stranded DNAs while those in liver tissues were found to be a mixture of plus- and minus-stranded DNAs. These results suggest that TTV replicates in the liver via a circular double-stranded DNA.

scholarly journals African Swine Fever Virus Gets Undressed: New Insights on the Entry Pathway

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Germán Andrés
Keyword(s):  
African Swine Fever Virus ◽  
Structural Complexity ◽  
African Swine Fever ◽  
Low Ph ◽  
Fever Virus ◽  
Dna Virus ◽  
Alternative Pathways ◽  
Entry Pathway ◽  
A Genome ◽  
Inner Envelope

ABSTRACT African swine fever virus (ASFV) is a large, multienveloped DNA virus composed of a genome-containing core successively wrapped by an inner lipid envelope, an icosahedral protein capsid, and an outer lipid envelope. In keeping with this structural complexity, recent studies have revealed an intricate entry program. This Gem highlights how ASFV uses two alternative pathways, macropinocytosis and clathrin-mediated endocytosis, to enter into the host macrophage and how the endocytosed particles undergo a stepwise, low pH-driven disassembly leading to inner envelope fusion and core delivery in the cytoplasm.

scholarly journals Hepatitis B Virus Polymerase Disrupts K63-Linked Ubiquitination of STING To Block Innate Cytosolic DNA-Sensing Pathways

2014 ◽  
Vol 89 (4) ◽  
pp. 2287-2300 ◽  
Author(s):  
Yinghui Liu ◽  
Jianhua Li ◽  
Jieliang Chen ◽  
Yaming Li ◽  
Weixia Wang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Innate Immune ◽  
Dna Sensing ◽  
Viral Polymerase ◽  
Dna Virus ◽  
Catalytic Function ◽  
B Virus ◽  
Foreign Dna

ABSTRACTThe cellular innate immune system recognizing pathogen infection is essential for host defense against viruses. In parallel, viruses have developed a variety of strategies to evade the innate immunity. The hepatitis B virus (HBV), a DNA virus that causes chronic hepatitis, has been shown to inhibit RNA helicase RIG-I-mediated interferon (IFN) induction. However, it is still unknown whether HBV could affect the host DNA-sensing pathways. Here we report that in transiently HBV-transfected Huh7 cells, the stably HBV-producing cell line HepAD38, and HBV-infected HepaRG cells and primary human hepatocytes, HBV markedly interfered with IFN-β induction and antiviral immunity mediated by the stimulator of interferon genes (STING), which has been identified as a central factor in foreign DNA recognition and antiviral innate immunity. Screening analysis demonstrated that the viral polymerase (Pol), but not other HBV-encoded proteins, was able to inhibit STING-stimulated interferon regulatory factor 3 (IRF3) activation and IFN-β induction. Moreover, the reverse transcriptase (RT) and the RNase H (RH) domains of Pol were identified to be responsible for the inhibitory effects. Furthermore, Pol was shown to physically associate with STING and dramatically decrease the K63-linked polyubiquitination of STING via its RT domain without altering the expression level of STING. Taken together, these observations suggest that besides its inherent catalytic function, Pol has a role in suppression of IFN-β production by direct interaction with STING and subsequent disruption of its K63-linked ubiquitination, providing a new mechanism for HBV to counteract the innate DNA-sensing pathways.IMPORTANCEAlthough whether and how HBV infection induces the innate immune responses are still controversial, it has become increasingly clear that HBV has developed strategies to counteract the pattern recognition receptor-mediated signaling pathways. Previous studies have shown that type I IFN induction activated by the host RNA sensors could be inhibited by HBV. However, it remains unknown whether HBV as a DNA virus utilizes evasion mechanisms against foreign DNA-elicited antiviral signaling. In recent years, the cytosolic DNA sensor and key adaptor STING has been demonstrated to be essential in multiple foreign DNA-elicited innate immune signalings. Here, for the first time, we report STING as a new target of HBV to antagonize IFN induction and identify the viral polymerase responsible for the inhibitory effect, thus providing an additional molecular mechanism by which HBV evades the innate immunity; this implies that in addition to its inherent catalytic function, HBV polymerase is a multifunctional immunomodulatory protein.

scholarly journals Structural Insight into African Swine Fever Virus A179L-Mediated Inhibition of Apoptosis

2017 ◽  
Vol 91 (6) ◽  
Author(s):  
Suresh Banjara ◽  
Sofia Caria ◽  
Linda K. Dixon ◽  
Mark G. Hinds ◽  
Marc Kvansakul
Keyword(s):  
Crystal Structures ◽  
African Swine Fever Virus ◽  
Three Dimensional ◽  
African Swine Fever ◽  
Fever Virus ◽  
Structural Basis ◽  
Dna Virus ◽  
Content Type ◽  
Antiapoptotic Proteins ◽  
Apoptosis Inhibition

ABSTRACT Programmed cell death is a tightly controlled process critical for the removal of damaged or infected cells. Pro- and antiapoptotic proteins of the Bcl-2 family are pivotal mediators of this process. African swine fever virus (ASFV) is a large DNA virus, the only member of the Asfarviridae family, and harbors A179L, a putative Bcl-2 like protein. A179L has been shown to bind to several proapoptotic Bcl-2 proteins; however, the hierarchy of binding and the structural basis for apoptosis inhibition are currently not understood. We systematically evaluated the ability of A179L to bind proapoptotic Bcl-2 family members and show that A179L is the first antiapoptotic Bcl-2 protein to bind to all major death-inducing mammalian Bcl-2 proteins. We then defined the structural basis for apoptosis inhibition of A179L by determining the crystal structures of A179L bound to both Bid and Bax BH3 motifs. Our findings provide a mechanistic understanding for the potent antiapoptotic activity of A179L by identifying it as the first panprodeath Bcl-2 binder and serve as a platform for more-detailed investigations into the role of A179L during ASFV infection. IMPORTANCE Numerous viruses have acquired strategies to subvert apoptosis by encoding proteins capable of sequestering proapoptotic host proteins. African swine fever virus (ASFV), a large DNA virus and the only member of the Asfarviridae family, encodes the protein A179L, which functions to prevent apoptosis. We show that A179L is unusual among antiapoptotic Bcl-2 proteins in being able to physically bind to all core death-inducing mammalian Bcl-2 proteins. Currently, little is known regarding the molecular interactions between A179L and the proapoptotic Bcl-2 members. Using the crystal structures of A179L bound to two of the identified proapoptotic Bcl-2 proteins, Bid and Bax, we now provide a three-dimensional (3D) view of how A179L sequesters host proapoptotic proteins, which is crucial for subverting premature host cell apoptosis.

scholarly journals DNA Virus Vectors for Vaccine Production in Plants: Spotlight on Geminiviruses

Vaccines ◽  
2014 ◽  
Vol 2 (3) ◽  
pp. 642-653 ◽  
Author(s):  
Kathleen Hefferon
Keyword(s):  
Vaccine Production ◽  
Dna Virus ◽  
Virus Vectors

An empirical test of the mutational landscape model of adaptation using a single-stranded DNA virus

2005 ◽  
Vol 37 (4) ◽  
pp. 441-444 ◽  
Author(s):  
Darin R Rokyta ◽  
Paul Joyce ◽  
S Brian Caudle ◽  
Holly A Wichman
Keyword(s):  
Empirical Test ◽  
Landscape Model ◽  
Dna Virus ◽  
Single Stranded Dna ◽  
Mutational Landscape

scholarly journals Tumores perianais provocados pelo herpes simples

2007 ◽  
Vol 27 (1) ◽  
pp. 93-95
Author(s):  
Sidney Roberto Nadal ◽  
Luis Roberto Manzione Nadal
Keyword(s):  
Herpes Simplex ◽  
Dna Virus

O Herpes simplex (HSV) é um DNA vírus que provoca afecções perianais, sendo considerada a causa mais comum das úlceras na região. Apesar da forma ulcerativa ser a mais conhecida, a literatura relata o aparecimento de lesões tumorais, nodulares ou hipertróficas relacionadas ao vírus. O exame proctológico mostra tumores dolorosos, achatados, com superfície recoberta por ulceração rasa e com bordas bem delimitadas, elevadas e lobuladas, localizados na margem anal e/ou no sulco interglúteo, algumas vezes imitando condilomas virais ou carcinoma. A anamnese revela instalação insidiosa com crescimento lento e progressivo, além da história de tratamentos anteriores para úlceras herpéticas. O diagnóstico diferencial com carcinoma impõe a realização de biópsia para confirmação histológica. Esse exame revela hiperplasia epitelial moderada e denso processo inflamatório com linfócitos e plasmócitos. Células gigantes e multinucleadas são observadas na epiderme. Os testes imunohistoquímicos sugerem o HSV. A opção terapêutica inicial deve ser o tratamento medicamentoso. Importante definir o diagnóstico etiológico para aliviar o desconforto e evitar operação radical desnecessária, e introduzir medicação anti-retroviral nos portadores do HIV para melhora da imunidade.

Transfer of a marine DNA virus fromEctocarpus toFeldmannia (Ectocarpales, Phaeophyceae): aberrant symptoms and restitution of the host

PROTOPLASMA ◽  
1993 ◽  
Vol 175 (3-4) ◽  
pp. 121-125 ◽  
Author(s):  
D. G. M�ller ◽  
Elisa Parodi
Keyword(s):  
Dna Virus

scholarly journals Crystal Structure of African Swine Fever Virus pS273R Protease and Implications for Inhibitor Design

2020 ◽  
Vol 94 (10) ◽  
Author(s):  
Guobang Li ◽  
Xiaoxia Liu ◽  
Mengyuan Yang ◽  
Guangshun Zhang ◽  
Zhengyang Wang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Structural Information ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Hydrolytic Activity ◽  
Viral Disease ◽  
Fever Virus ◽  
Dna Virus ◽  
Core Domain ◽  
The Core

ABSTRACT African swine fever (ASF) is a highly contagious hemorrhagic viral disease of domestic and wild pigs that is responsible for serious economic and production losses. It is caused by the African swine fever virus (ASFV), a large and complex icosahedral DNA virus of the Asfarviridae family. Currently, there is no effective treatment or approved vaccine against the ASFV. pS273R, a specific SUMO-1 cysteine protease, catalyzes the maturation of the pp220 and pp62 polyprotein precursors into core-shell proteins. Here, we present the crystal structure of the ASFV pS273R protease at a resolution of 2.3 Å. The overall structure of the pS273R protease is represented by two domains named the “core domain” and the N-terminal “arm domain.” The “arm domain” contains the residues from M1 to N83, and the “core domain” contains the residues from N84 to A273. A structure analysis reveals that the “core domain” shares a high degree of structural similarity with chlamydial deubiquitinating enzyme, sentrin-specific protease, and adenovirus protease, while the “arm domain” is unique to ASFV. Further, experiments indicated that the “arm domain” plays an important role in maintaining the enzyme activity of ASFV pS273R. Moreover, based on the structural information of pS273R, we designed and synthesized several peptidomimetic aldehyde compounds at a submolar 50% inhibitory concentration, which paves the way for the design of inhibitors to target this severe pathogen. IMPORTANCE African swine fever virus, a large and complex icosahedral DNA virus, causes a deadly infection in domestic pigs. In addition to Africa and Europe, countries in Asia, including China, Vietnam, and Mongolia, were negatively affected by the hazards posed by ASFV outbreaks in 2018 and 2019, at which time more than 30 million pigs were culled. Until now, there has been no vaccine for protection against ASFV infection or effective treatments to cure ASF. Here, we solved the high-resolution crystal structure of the ASFV pS273R protease. The pS273R protease has a two-domain structure that distinguishes it from other members of the SUMO protease family, while the unique “arm domain” has been proven to be essential for its hydrolytic activity. Moreover, the peptidomimetic aldehyde compounds designed to target the substrate binding pocket exert prominent inhibitory effects and can thus be used in a potential lead for anti-ASFV drug development.

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