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immune protection conferred by the baculovirus-related glycoprotein of thogoto virus (orthomyxoviridae).the coding region of segment 4 of thogoto (tho) virus, a tick-borne member of the orthomyxoviridae, was expressed in a baculovirus system under the control of the polyhedrin promoter. this construct expressed authentic envelope glycoprotein as determined by size and antigenic reactivity with a panel of monoclonal antibodies (mabs). immunization of hamsters with spodoptera frugiperda (sf21) cells infected with the recombinant baculovirus induced neutralizing and protective antibodies against viru ...19957483270
mx1 but not mxa confers resistance against tick-borne dhori virus in mice.the interferon-induced nuclear mx1 protein is responsible for innate resistance of mice to influenza virus. it has been unclear why mice are equipped with a powerful and specific defense mechanism against influenza viruses for which they are not natural hosts. here, we show that dhori virus, an influenza-like virus transmitted by ticks and known to infect small mammals, is sensitive to the mx1 resistance mechanism. influenza virus-susceptible balb/c and c57bl/6 mice (lacking a functional mx1 gen ...19957645224
human mxa protein inhibits tick-borne thogoto virus but not dhori virus.thogoto and dhori viruses are tick-borne orthomyxoviruses infecting humans and livestock in africa, asia, and europe. here, we show that human mxa protein is an efficient inhibitor of thogoto virus but is inactive against dhori virus. when expressed in the cytoplasm of stably transfected cell lines, mxa protein interfered with the accumulation of thogoto viral rna and proteins. likewise, mxa(r645), a mutant mxa protein known to be active against influenza virus but inactive against vesicular sto ...19957745744
tick-borne thogoto virus infection in mice is inhibited by the orthomyxovirus resistance gene product mx1.we show that tick-transmitted thogoto virus is sensitive to interferon-induced nuclear mx1 protein, which is known for its specific antiviral action against orthomyxoviruses. influenza virus-susceptible balb/c mice (lacking a functional mx1 gene) developed severe disease symptoms and died within days after intracerebral or intraperitoneal infection with a lethal challenge dose of thogoto virus. in contrast, mx1-positive congenic, influenza virus-resistant balb.a2g-mx1 mice remained healthy and s ...19957884909
amblyomma variegatum (acari: ixodidae): mechanism and control of arbovirus secretion in tick saliva.saliva is considered to be the conduit by which pathogens are transmitted from blood-sucking arthropod vectors to their vertebrate hosts, but supporting evidence for this is fragmentary. to determine if thogoto (tho) virus, a tick-borne member of the influenza virus family, is transmitted via tick saliva, and whether virus replication is a prerequisite for such transmission, two experimental conditions were compared: (1) "biological transmission" and (2) "mechanical transmission." in (1), tho vi ...19968631383
thogoto and dhori virus replication is blocked by inhibitors of cellular polymerase ii activity but does not cause shutoff of host cell protein synthesis.tick-transmitted thogoto and dhori viruses share structural and genetic properties with the influenza viruses. here, we compare different steps of their replication cycle in mammalian cells in comparison with influenza a virus. viral antigens of both viruses accumulated in the nuclei of infected cells, suggesting a nuclear phase of viral replication. furthermore, as observed with influenza viruses, transcription of thogoto and dhori viruses was inhibited by alpha-amanitin and actinomycin d, sugg ...19968856036
nucleoprotein viral rna and mrna of thogoto virus: a novel "cap-stealing" mechanism in tick-borne orthomyxoviruses?tick-borne thogoto virus (thov) represents the prototype virus of a new genus in the orthomyxoviridae family. its genome consists of six segments of negative-sense, single-stranded rna. we have cloned and sequenced the fifth genomic segment, which codes for the viral nucleoprotein (np). the deduced amino acid sequence shows 43% similarity to the np of dhori virus, a related tick-transmitted orthomyxovirus, and about 14% sequence similarity to those of the influenza viruses. to reveal the mechani ...19968970956
the 5' ends of thogoto virus (orthomyxoviridae) mrnas are homogeneous in both length and sequence.thogoto (tho) virus is a tick-borne member of the orthomyxoviridae whose genome consists of six segments of linear, negative sense, single-stranded rna. to gain insight into the mechanism by which viral mrna transcripts are initiated, poly(a)+ rna isolated from tho virus-infected cells was characterized by (i) primer extension experiments, (ii) immunoprecipitation studies with an anticap monoclonal antibody, (iii) direct sequencing analysis of the isolated rna, and (iv) cloning and sequencing of ...19968971034
dominant-negative mutants of human mxa protein: domains in the carboxy-terminal moiety are important for oligomerization and antiviral activity.human mxa protein is an interferon-induced 76-kda gtpase that exhibits antiviral activity against several rna viruses. wild-type mxa accumulates in the cytoplasm of cells. tmxa, a modified form of wild-type mxa carrying a foreign nuclear localization signal, accumulates in the cell nucleus. here we show that mxa protein is translocated into the nucleus together with tmxa when both proteins are expressed simultaneously in the same cell, demonstrating that mxa molecules form tight complexes in liv ...19979060610
conserved vrna end sequences of thogoto-orthomyxovirus suggest a new panhandle structure.panhandles are dsrna structures formed by conserved sequences at the 5' and 3' ends of the influenza virus genomic rna. they consist of two stems separated by a flexible bulge and serve as promoter for the viral polymerase. in the outer stem, melting of base pairs is a prerequisite for initiation of transcription. we compared the terminal sequences of thogoto virus (thov), a tick-borne orthomyxovirus, with those of influenza virus. despite their overall similarity, the first u downstream of the ...19979191867
the fourth genus in the orthomyxoviridae: sequence analyses of two thogoto virus polymerase proteins and comparison with influenza viruses.the tick-borne thogoto virus (thov) is the type species of a newly recognized fourth genus, thogotovirus, in the family orthomyxoviridae. because of the distant relationship of thov with the influenza viruses, determination of its genomic information can potentially be used to identify important domains in influenza virus proteins. we have determined the complete nucleotide sequence of the second longest rna segment of thov. the molecule comprises 2212 nucleotides with a single large open readin ...19979282786
in vitro polymerase activity of thogoto virus: evidence for a unique cap-snatching mechanism in a tick-borne orthomyxovirus.the tick-borne thogoto virus (thov) is the type species of a new genus in the family orthomyxoviridae. its genome comprises six segments of single-stranded, negative-sense rna. each segment possesses conserved regions of semicomplementary nucleotides at the 3' and 5' termini which strongly resemble those of influenza virus. an in vitro polymerase assay based on reconstituted thov viral cores was developed, and activity was shown to rely on an interaction between the conserved 3'- and 5'-terminal ...19979343188
striking conformational similarities between the transcription promoters of thogoto and influenza a viruses: evidence for intrastrand base pairing in the 5' promoter arm.in the accompanying report, we describe an in vitro polymerase assay based on reconstituted thogoto virus (thov) cores which provided evidence of a double-stranded vrna promoter consisting of both the 3' and 5' sequences of vrna (m. b. leahy, j. t. dessens, and p. a. nuttall, j. virol. 71:8347-8351, 1997). this system was used to investigate further the thov vrna promoter structure by using short, synthetic vrna promoters. the results obtained show that interstrand base pairing between residues ...19979343189
mx1 sensitivity: batken virus is an orthomyxovirus closely related to dhori virus.batken virus, isolated from mosquitoes and ticks, was tentatively classified as a member of the family bunyaviridae. here we show that batken virus is inhibited by the interferon-induced mx1 protein of mice which selectively blocks the growth of orthomyxoviruses, including thogoto and dhori viruses. furthermore, we show that batken virus multiplication is characterized by accumulation of viral proteins in the nucleus and by budding of viral particles from the cell surface. serological cross-reac ...19979349464
an endonuclease switching mechanism in the virion rna and crna promoters of thogoto orthomyxovirus.an in vitro assay was developed to investigate endonuclease activity of thogoto virus, a tick-borne orthomyxovirus. endonuclease activity relied on an interaction between the 3' and 5' termini of virion rna (vrna) and not those of crna. evidence was obtained that cap structures are cleaved directly from cap donors and that cleavage does not occur after pyrimidines. a 5' hook structure, present in the vrna promoter but not the crna promoter, was introduced into crna promoter mutants. these mutant ...19989499090
the thogoto orthomyxovirus crna promoter functions as a panhandle but does not stimulate cap snatching in vitro.the crna promoter of thogoto virus, a tick-borne orthomyxovirus, was investigated using an in vitro polymerase assay based on purified viral cores and synthetic oligoribonucleotides corresponding to the 3' and 5' ends of crna. in vitro polymerase activity relied on an interaction between the 3' and 5' ends of crna and was apg primer-dependent. mutational analysis of the promoter showed that interstrand base-pairing of residues 11 and 12 of the 3' promoter arm with residues 10 and 11 of the 5' pr ...19989519823
displaced tick-parasite interactions at the host interface.reciprocal interactions of parasites transmitted by blood-sucking arthropod vectors have been studied primarily at the parasite-host and parasite-vector interface. the third component of this parasite triangle, the vector-host interface, has been largely ignored. now there is growing realization that reciprocal interactions between arthropod vectors and their vertebrate hosts play a pivotal role in the survival of arthropod-borne viruses, bacteria, and protozoa. the vector-host interface is the ...19989695111
mx1-based resistance to thogoto virus in a2g mice is bypassed in tick-mediated virus delivery.the interferon-induced mouse mx1 protein has intrinsic antiviral activity against orthomyxoviruses, including thogoto virus. thus, mx1(+) a2g mice are apparently resistant to infection following needle- or tick-borne virus challenge. however, tick-borne challenge and, to a lesser degree, injection of virus mixed with tick salivary gland extract resulted in virus transmission to uninfected ticks feeding on the a2g mice. the data indicate that immunomodulatory components in tick saliva can overcom ...19989733885
a classical bipartite nuclear localization signal on thogoto and influenza a virus nucleoproteins.we have previously shown that the nucleoprotein (np) of thogoto virus (thov), a tick-borne member of the orthomyxoviridae family, accumulates in the cell nucleus. here we demonstrate that thov np contains a motif (krxxxxxxxxxktkk) at amino acid positions 179-193 that represents a classical bipartite nuclear localization signal (nls). this sequence motif (named cnls) was able to translocate a cytoplasmic 80-kda reporter protein into the nucleus. targeted mutations substituting lysines for alanine ...19989770415
in vivo reconstitution of active thogoto virus polymerase: assays for the compatibility with other orthomyxovirus core proteins and template rnas.tick-borne thogoto virus (thov), the prototype of a new genus in the orthomyxoviridae family, contains six single-stranded rna segments of negative polarity. four of them encode gene products that correspond to the influenza virus pb1, pb2, pa and np core proteins. here we describe an in vivo system in which the expression of a thov model rna is driven by thov core proteins synthesized from cloned cdnas. our results demonstrated the biological activity of our cloned genes and showed that the thr ...19989879758
gtp-bound human mxa protein interacts with the nucleocapsids of thogoto virus (orthomyxoviridae).human mxa protein is an interferon-induced member of the dynamin superfamily of large gtpases. mxa inhibits the multiplication of several rna viruses, including thogoto virus, an influenza virus-like orthomyxovirus transmitted by ticks. previous studies have indicated that gtp binding is required for antiviral activity, but the mechanism of action is still unknown. here, we have used an in vitro cosedimentation assay to demonstrate, for the first time, a gtp-dependent interaction between mxa gtp ...19999933640
interferon-induced human mxa gtpase blocks nuclear import of thogoto virus nucleocapsids.interferon-induced human mxa protein belongs to the dynamin superfamily of large gtpases. it exhibits antiviral activity against a variety of rna viruses, including thogoto virus, an influenza virus-like orthomyxovirus transmitted by ticks. here, we report that mxa blocks the transport of thogoto virus nucleocapsids into the nucleus, thereby preventing transcription of the viral genome. this interaction can be abolished by a mab that neutralizes the antiviral activity of mxa. our results reveal ...199910051598
human mxa protein protects mice lacking a functional alpha/beta interferon system against la crosse virus and other lethal viral infections.the human mxa protein is part of the antiviral state induced by alpha/beta interferon (ifn-alpha/beta). mxa inhibits the multiplication of several rna viruses in cell culture. however, its antiviral potential in vivo has not yet been fully explored. we have generated mxa-transgenic mice that lack a functional ifn system by crossing mxa-transgenic mice constitutively expressing mxa with genetically targeted (knockout) mice lacking the beta subunit of the ifn-alpha/beta receptor (ifnar-1(-/-) mice ...199910400797
isolation of thogoto virus (orthomyxoviridae) from the banded mongoose, mongos mungo (herpestidae), in uganda.small wild vertebrates were trapped during an investigation into possible vertebrate reservoirs of o'nyong-nyong (onn) fever virus in uganda in 1997. antibody neutralization test results and virus isolation attempts were negative for onn virus, confirming the work of earlier investigators, who also failed to find evidence for a nonhuman onn virus reservoir. in the course of these onn virus studies, thogoto virus was isolated from one of eight banded mongooses (mongos mungo). this is the first is ...199910466973
pb2 polymerase subunit of thogoto virus (orthomyxoviridae family).thogoto virus (thov) represents a new genus in the family orthomyxoviridae. the three polymerase subunits pb1, pb2, and pa initiate transcription by a unique cap-stealing mechanism that involves the cleavage of only the m(7)gpppam structure from cellular hnrnas. here, we report the cloning of the longest genomic segment of thov coding for pb2. it comprises 2,375 nucleotides encoding a single large open reading frame flanked by the conserved terminal regions typical for orthomyxoviruses. the dedu ...199910486113
mxa gtpase blocks reporter gene expression of reconstituted thogoto virus ribonucleoprotein complexes.human mxa protein accumulates in the cytoplasm of interferon-treated cells and inhibits the multiplication of several rna viruses, including thogoto virus (thov), a tick-borne orthomyxovirus that transcribes and replicates its genome in the cell nucleus. the antiviral mechanism of mxa was investigated by using two alternative minireplicon systems in which recombinant viral ribonucleoprotein complexes (vrnps) of thov were reconstituted from cloned cdnas. a chloramphenicol acetyltransferase report ...200010590150
rescue of synthetic rnas into thogoto and influenza a virus particles using core proteins purified from thogoto virus.the ribonucleoprotein (rnp) complexes of thogoto virus (thov), a tick-borne orthomyxovirus, have been purified from detergent-lysed virions. the purified rnps were then disrupted by centrifugation through a cscl-glycerol gradient to obtain fractions highly enriched in nucleoprotein (np) and virtually devoid of viral genomic rna. when these np-enriched fractions were incubated with a synthetic thov-like rna, and the mixtures were transfected into thov-infected cells, the synthetic rna was express ...200010773317
a monomeric gtpase-negative mxa mutant with antiviral activity.mxa is a large, interferon-induced gtpase with antiviral activity against rna viruses. it forms large oligomers, but whether oligomerization and gtpase activity are important for antiviral function is not known. the mutant protein mxa(l612k) carries a lysine-for-leucine substitution at position 612 and fails to form oligomers. here we show that monomeric mxa(l612k) lacks detectable gtpase activity but is capable of inhibiting thogoto virus in transiently transfected vero cells or in a thogoto vi ...200010933733
thogoto virus matrix protein is encoded by a spliced mrna.thogoto virus (thov) is a tick-transmitted orthomyxovirus with a segmented, negative-stranded rna genome. in this study, we investigated the coding strategy of rna segment 6 and found that it contains 956 nucleotides and codes for the matrix (m) protein. the full-length cdna contains a single, long reading frame that lacks a stop codon but has coding capacity for a putative 35-kda protein. in contrast, the m protein of thov has an apparent molecular mass of 29 kda as assessed by polyacrylamide g ...200011044123
formation of virus-like particles from cloned cdnas of thogoto virus.thogoto virus (thov) is the type species of tick-transmitted orthomyxoviruses. here, we describe the generation of virus-like particles (vlp) of thov from cloned cdnas. to synthesize the six structural proteins of thov in mammalian cells, we used t7-controlled expression plasmids and a recombinant vaccinia virus producing t7 rna polymerase. a minireplicon encoding a reporter gene flanked by thov promoter sequences was expressed by the cellular rna polymerase i. the recombinant proteins were func ...200011086115
intra-stadial tick-borne thogoto virus (orthomyxoviridae) transmission: accelerated arbovirus transmission triggered by host death.haematophagous insect vectors of arthropod-borne viruses (arboviruses) feed repeatedly. consequently, they can transmit arboviruses to more than one host during the same developmental stage (intra-stadial transmission). by contrast, ixodid ticks generally feed only once at each parasitic stage (larva, nymph, and adult) and hence they have only one opportunity for tickborne virus transmission per stadium (inter-stadial transmission). under natural conditions, tick-infested hosts may die (from dis ...200111315177
rescue of recombinant thogoto virus from cloned cdna.thogoto virus (thov) is a tick-transmitted orthomyxovirus with a genome consisting of six negative-stranded rna segments. to rescue a recombinant thov, the viral structural proteins were produced from expression plasmids by means of a vaccinia virus expressing the t7 rna polymerase. genomic virus rnas (vrnas) were generated from plasmids under the control of the rna polymerase i promoter. using this system, we could efficiently recover recombinant thov following transfection of 12 plasmids into ...200111533190
interferon-induced rat mx proteins confer resistance to rift valley fever virus and other arthropod-borne viruses.mx proteins belong to the interferon (ifn)-induced antiviral defense. the rat genome contains three mx genes, ratmx1, ratmx2, and ratmx3. the mx gene products differ in their subcellular localization and antiviral specificity. the nuclear ratmx1 protein confers resistance to influenza a virus, and the cytoplasmic ratmx2 is active against vesicular stomatitis virus (vsv), whereas the cytoplasmic ratmx3 protein is antivirally inactive. to investigate the antiviral potential of the rat mx proteins ...200111576460
antigenic variation among isolates of infectious salmon anaemia virus correlates with genetic variation of the viral haemagglutinin gene.infectious salmon anaemia virus (isav), an orthomyxovirus-like virus, is an important fish pathogen in marine aquaculture. virus neutralization of 24 isav isolates in the to cell line using rabbit antisera to the whole virus and comparative sequence analysis of their haemagglutinin (ha) genes have allowed elaboration on the variation of isav isolates. the 24 viruses were neutralized to varying degrees, revealing two major antigenic groups, one american and one european. sequence analysis of the ...200111714961
phylogeny of thogoto virus.thogoto virus is a tick-borne member of the family orthomyxoviridae. previously, based on the similarity in antigenic relationship by cross-neutralization test, all virus strains were concluded to have derived from the same origin. in this study, we obtained partial gene sequences of 4 genes (pb1-like protein, pa-like protein, glycoprotein, and nucleoprotein) of 8 thogoto virus strains isolated in africa, asia, and europe and studied the genetic variation and phylogeny. unrooted phylogenetic tre ...200111724276
pseudotyping autographa californica multicapsid nucleopolyhedrovirus (acmnpv): f proteins from group ii npvs are functionally analogous to acmnpv gp64.gp64, the major envelope glycoprotein of budded virions of the baculovirus autographa californica multicapsid nucleopolyhedrovirus (acmnpv), is involved in viral attachment, mediates membrane fusion during virus entry, and is required for efficient virion budding. thus, gp64 is essential for viral propagation in cell culture and in animals. recent genome sequences from a number of baculoviruses show that only a subset of closely related baculoviruses have gp64 genes, while other baculoviruses ha ...200211992001
salivary fluid secretion in the ixodid tick rhipicephalus appendiculatus is inhibited by thogoto virus infection.adult rhipicephatus appendiculatus ticks, infected with thogoto (tho) virus or control, were fed on guinea pigs and removed at intervals throughout the feeding cycle. salivary fluid secretion was measured by an in vitro technique. the salivary glands of infected, partially-fed ticks secreted fluid in vitro at about 75% the rate of controls, but the difference between infected and controls among engorged ticks was not statistically significant. basal and da-stimulated levels of cyclic amp (camp) ...200112171274
[the isolation of dhori viruses (orthomyxoviridae, thogotovirus) and crimean-congo hemorrhagic fever virus (bunyaviridae, nairovirus) from the hare (lepus europaeus) and its ticks hyalomma marginatum in the middle zone of the volga delta, astrakhan region, 2001].in august, 2001, in the middle zone of the delta of the volga river, the astrakhan region, during investigation of the natural foci of west nile fever and crimean--congo hemorrhagic fever (cchf), the material from the hare (lepus europaeus, pallas, 1778 (lagomorpha, leporidae) and collected from it the ticks hyalomna marginatum koch 1844, was obtained. 4 strains of dhori virus (orthomyxoviridae, thogotovirus) and 2 strains of cchf virus (bunyaviridae, nairovirus) were isolated. this is the first ...200212271723
novel gene product of thogoto virus segment 6 codes for an interferon antagonist.thogoto virus (thov) is a tick-transmitted orthomyxovirus with a genome of six negative-stranded rna segments. the sixth segment encodes two different transcripts: a spliced transcript that is translated into the matrix protein (m) and an unspliced transcript. here, we report that the unspliced transcript encodes an elongated form of m named ml. a thov isolate deficient in ml expression was an efficient interferon inducer, whereas ml-expressing wild-type strains were poor interferon inducers. th ...200312552016
trafficking of viral genomic rna into and out of the nucleus: influenza, thogoto and borna disease viruses.most rna viruses that lack a dna phase replicate in the cytoplasm. however, several negative-stranded rna viruses such as influenza, thogoto, and borna disease viruses replicate their rnas in the nucleus, taking advantage of the host cell's nuclear machinery. a challenge faced by these viruses is the trafficking of viral components into and out of the nucleus through the nuclear membrane. the genomic rnas of these viruses associate with proteins to form large complexes called viral ribonucleopro ...200312921991
rhipicephalus appendiculatus (acari: ixodidae): dynamics of thogoto virus infection in female ticks during feeding on guinea pigs.engorged nymphs (rhipicephalus appendiculatus) were inoculated parenterally with thogoto (tho) virus (approximately 1 microl per nymph; 10(6)-10(7) pfu/ml). the adult females which resulted were used as the source of infected ticks for this study. hemolymph, salivary glands, synganglion, gut, ovary, and malpighian tubules were collected on each day of the blood meal and titrated for tho virus by plaque assay. the percent of tissues infected with virus was 16% or less on the day of attachment. pe ...200312932755
[circulation of west nile virus (flaviviridae, flavivirus) and some other arboviruses in the ecosystems of volga delta, volga-akhtuba flood-lands and adjoining arid regions (2000-2002)].comprehensive virological, serological as well as genetic studies of the ecology of west nile virus (wnv) as well as of some other arboviruses were undertaken in different ecosystems in the territories of the astrakhan region and of the kalmyk republic. the main carriers (mosquitoes, ticks, birds and mammals) were defined as involved in the circulation of viruses within the natural and anthropogenic biocenosis. phylogenetic examinations of isolated strains and samples, which were positive in rt- ...200415188655
orthomyxovirus replication, transcription, and polyadenylation.efficient in vitro and in vivo systems are now in place to study the role of viral proteins in replication and/or transcription, the regulation of these processes, polyadenylation of viral mrnas, the viral promoter structures, or the significance of noncoding regions for virus replication. in this chapter, we review the status of current knowledge of the orthomyxovirus rna synthesis.200415298169
thogoto virus lacking interferon-antagonistic protein ml is strongly attenuated in newborn mx1-positive but not mx1-negative mice.the thogoto virus ml protein suppresses interferon synthesis in infected cells. nevertheless, a virus mutant lacking ml remained highly pathogenic in standard laboratory mice. it was strongly attenuated, however, in mice carrying the interferon-responsive mx1 gene found in wild mice, demonstrating that enhanced interferon synthesis is protective only if appropriate antiviral effector molecules are present. our study shows that the virulence-enhancing effects of some viral interferon antagonists ...200415452266
functional comparison of the two gene products of thogoto virus segment 6.the sixth genomic segment of thogoto virus (thov) encodes two proteins, the viral matrix protein (m) and an accessory protein with an interferon (ifn)-antagonistic function named ml. m and ml are shown in this study to be structural components of the virion. using an in vivo system based on the reconstitution of functional thov ribonucleoprotein complexes from cloned cdnas, it was demonstrated that m has an inhibitory effect on the viral rna-dependent rna polymerase (rdrp) and is essential for t ...200415557243
thogoto virus ml protein suppresses irf3 function.the thogoto virus (thov) is a member of the family orthomyxoviridae. it prevents induction of alpha/beta interferons (ifn) in cell culture and in vivo via the action of the viral ml protein. phenotypically, the effect of thov ml resembles that of the ns1 protein of influenza a virus (fluav) in that it blocks the expression of ifn genes. ifn expression depends on ifn regulatory factor 3 (irf3). upon activation, irf3 forms homodimers and accumulates in the nucleus where it binds the transcriptiona ...200515582653
araguari virus, a new member of the family orthomyxoviridae: serologic, ultrastructural, and molecular characterization.this paper reports the results of serologic, structural, biochemical, and genetic studies indicating that araguari virus, a previously unassigned viral agent, is a member of the family orthomyxoviridae and genus thogotovirus. araguari virus has six rna fragments; biologically, it shares several properties with other viruses in the family orthomyxoviridae. nucleotide sequencing of the rna segments 4 (glycoprotein) and 5 (nucleoprotein) of araguari virus aligned with the orthomyxoviruses, showing ...200516354811
dhori virus (orthomyxoviridae: thogotovirus) infection in mice: a model of the pathogenesis of severe orthomyxovirus infection.after intranasal, subcutaneous, or intraperitoneal infection with dhori virus (dhov), adult mice developed a fulminant and uniformly fatal illness with many of the clinical and pathologic findings seen in mice infected with h5n1 highly pathogenic avian influenza a virus. histopathologic findings in lungs of dhov-infected mice consisted of hemorrhage, inflammation, and thickening of the interstitium and the alveolar septa and alveolar edema. extra-pulmonary findings included hepatocellular necros ...200717426188
functional analysis of the transmembrane (tm) domain of the autographa californica multicapsid nucleopolyhedrovirus gp64 protein: substitution of heterologous tm domains.gp64, the major envelope glycoprotein of the autographa californica multicapsid nucleopolyhedrovirus (acmnpv) budded virion, is important for host cell receptor binding and mediates low-ph-triggered membrane fusion during entry by endocytosis. in the current study, we examined the functional role of the acmnpv gp64 transmembrane (tm) domain by replacing the 23-amino-acid gp64 tm domain with corresponding tm domain sequences from a range of viral and cellular type i membrane proteins, including o ...200818216100
proteomics computational analyses suggest that baculovirus gp64 superfamily proteins are class iii penetrenes.members of the baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group i nucleopolyhedroviruses (npv) form the gp64 superfamily. the structure of these viral penetrenes has not been determined. the gp64 superfamily includes the glycoprotein (gp) encoded by members of the thogotovirus genus of the orthomyxoviridae. the entry proteins of other ...200818282283
[in vitro activity of russian ribavirin on the models of crimean-congo hemorrhagic fever virus, rift valley fever virus, and tahyna and dhori viruses].the high activity of ribavirin made by effective biotechnology in russia was established in in vitro experiments using the models crimean-congo hemorrhagic fever virus, rift valley fever virus, and tahyna and dhori viruses, which suggests that it is promising in using the drug in the treatment of infection with these viruses.200818318134
dhori virus (orthomyxoviridae: thogotovirus) infection of mice produces a disease and cytokine response pattern similar to that of highly virulent influenza a (h5n1) virus infection in humans.mice infected with dhori virus (dhov) develop a fulminant, systemic, and uniformly fatal illness that has many of the clinical and pathologic findings seen in h5n1 influenza a virus infection. however, the role of host's immune response in dhov infection remains unclear. in this study, the concentrations of 23 inflammatory cytokines and chemokines were measured in the liver, lungs, and sera of mice during the course of dhov infection. liver function, level of viremia, and hematologic response we ...200818385368
[isolation of influenza virus a (orthomyxoviridae, influenza a virus), dhori virus (orthomyxoviridae, thogotovirus), and newcastle's disease virus (paromyxoviridae, avulavirus) on the malyi zhemchuzhnyi island in the north-western area of the caspian sea].the paper presents the results of the 2003 and 2006 environmental virological monitoring surveys on the malyi zhemchuzhnyi island where a large breeding colony of sea gull (laridae) is located. in the past several years, expansion of cormorants (phalacrocorax carbo) has enhanced the intensity of populational interactions. the investigators isolated 13 strains of influenza a virus (orthomyxoviridae, influenza a virus) subtype h13n1 (from sea gulls (n = 4), cormorants (n = 9) 1 strain of dhori vir ...200818590134
[serological monitoring of arbovirus infections in the estuary of the kuban river (the 2006-2007 data)].solid-phase enzyme immunoassay, neutralization test, and the hemagglutination-inhibition test were used to study the sera from human beings (152 samples), agricultural animals (n = 77), hares (n = 3), and wild birds (n = 69), collected in 2006-2007 in the kuban river estuary (temryuk district, krasnodar territory). there were specific antibodies against viruses of west nile (wh), tick-borne encephalitis (tbe) (flaviviridae, flavivirus), sindbis (togaviridae, alphavirus), the antigenic complex of ...200818756814
the interferon antagonist ml protein of thogoto virus targets general transcription factor iib.the ml protein of thogoto virus, a tick-transmitted orthomyxovirus, is a splice variant of the viral matrix protein and antagonizes the induction of antiviral type i interferon (ifn). here we identified the general rna polymerase ii transcription factor iib (tfiib) as an ml-interacting protein. overexpression of tfiib neutralized the inhibitory effect of ml on irf3-mediated promoter activation. moreover, a recombinant virus expressing a mutant ml protein unable to bind tfiib was severely impaire ...200818768974
the pre-transmembrane domain of the autographa californica multicapsid nucleopolyhedrovirus gp64 protein is critical for membrane fusion and virus infectivity.the envelope glycoprotein, gp64, of the baculovirus autographa californica multicapsid nucleopolyhedrovirus (acmnpv) is a class iii viral fusion protein that mediates ph-triggered membrane fusion during virus entry. viral fusion glycoproteins from many viruses contain a short region in the ectodomain and near the transmembrane domain, referred to as the pre-transmembrane (ptm) domain. in some cases, the ptm domain is rich in aromatic amino acids and plays an important role in membrane fusion. al ...200919692475
thogoto virus ml protein is a potent inhibitor of the interferon regulatory factor-7 transcription factor.the tick-transmitted orthomyxovirus thogoto virus (thov) encodes the ml protein acting as a viral suppressor of the host interferon (ifn) system. here, we describe that type i ifn is strongly induced in primary mouse embryo fibroblasts as well as plasmacytoid dendritic cells upon infection with a thov mutant lacking the ml gene. however, wild-type thov encoding ml suppresses induction of ifn by preventing the activation of members of the ifn regulatory factor (irf) family. we found that reporter ...201019812269
temporal and spatial resolution of type i and iii interferon responses in vivo.although the action of interferons (ifns) has been extensively studied in vitro, limited information is available on the spatial and temporal activation pattern of ifn-induced genes in vivo. we created bac transgenic mice expressing firefly luciferase under transcriptional control of the mx2 gene promoter. expression of the reporter with regard to onset and kinetics of induction parallels that of mx2 and is thus a hallmark for the host response. substantial constitutive expression of the reporte ...201020573823
interspecies and intraspecies transmission of influenza a viruses: viral, host and environmental factors.influenza a viruses are enveloped viruses belonging to the family orthomyxoviridae that encompasses four more genera: influenza b, influenza c, isavirus and thogotovirus. type a viruses belong to the only genus that is highly infectious to a variety of mammalian and avian species. they are divided into subtypes based on two surface glycoproteins, the hemagglutinin (ha) and neuraminidase (na). so far, 16 ha and 9 na subtypes have been identified worldwide, making a possible combination of 144 sub ...201020591213
the cytoplasmic location of chicken mx is not the determining factor for its lack of antiviral activity.chicken mx belongs to the mx family of interferon-induced dynamin-like gtpases, which in some species possess potent antiviral properties. conflicting data exist for the antiviral capability of chicken mx. reports of anti-influenza activity of alleles encoding an asn631 polymorphism have not been supported by subsequent studies. the normal cytoplasmic localisation of chicken mx may influence its antiviral capacity. here we report further studies to determine the antiviral potential of chicken mx ...201020808435
thogoto virus infection induces sustained type i interferon responses that depend on rig-i-like helicase signaling of conventional dendritic cells.type i interferon (ifn-α/β) induction upon viral infection contributes to the early antiviral host defense and ensures survival until the onset of adaptive immunity. many viral infections lead to an acute, transient ifn expression which peaks a few hours after infection and reverts to initial levels after 24 to 36 h. robust ifn expression often is conferred by specialized plasmacytoid dendritic cells (pdc) and may depend on positive-feedback amplification via the type i ifn receptor (ifnar). her ...201020861272
[taxonomic structure of orthomyxoviridae: current views and immediate prospects].analysis of taxonomic structure of orthomyxoviridae was undertaken in view of its anticipated evolution. four concepts of circulation of influenza a viruses in the biosphere are discussed, viz. anthrponose, zooanthroponose, metastrongilose, and protozoan. all of them may be considered in the framework of the general zooantroponose concept. influenza b and c viruses can not be regarded as strictly anthroponose. comparative molecular-genetic analysis of the genus thogotovirus provides a basis for ...201121786592
Genomic and antigenic characterization of Jos virus.Jos virus (JOSV), originally isolated in Jos, Nigeria in 1967, has remained unclassified despite cultivation in tissue culture, development of animal models of infection and implementation of seroprevalence surveys for infection. Here we report genetic, ultrastructural and serologic evidence that JOSV is an orthomyxovirus distinct from but phylogenetically related to viruses of the genus Thogotovirus.201121994326
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