| crimean-congo hemorrhagic fever, thogoto, dugbe, and jos viruses isolated from ixodid ticks in ethiopia. | from 1974 through 1976, u.s. naval medical research unit no. 5 isolated 25 strain of tick-borne virus in infant mice from 410 pools containing over 6,000 ticks, and one strain from a bird and one strain from a rodent collected in central and southern ethiopia. of these, 17 were identified as known viruses previously found in west central and east africa. there were 8 strains of jos virus from amblyomma ticks; 7 strains of dugbe virus from a bird, a rodent and from ticks; 1 strains of crimean-con ... | 1978 | 98066 |
| a serological survey for thogoto virus in humans, domestic mammals, and rats in egypt. | | 1979 | 541586 |
| [isolation of thogoto virus from amblyomma and boophilus ticks in central africa]. | a survey has been carried out in the cameroons and the central african republic about the role of the ticks in the ecology of arboviruses in central africa. attempts for virus isolation were made for 12,678 amblyomma variegatum, 3,276 boophilus decoloratus and 1,769 boophilus annulatus, by inoculation into suckling mice. from 968 pools which were inoculated, 20 yielded isolates which were identified to thogoto virus. considering previously published results concerning tick-borne virus isolations ... | 1976 | 1037382 |
| identification of viral structural polypeptides of thogoto virus (a tick-borne orthomyxo-like virus) and functions associated with the glycoprotein. | thogoto (tho) virus is a tick-borne virus which shares morphological and genetic features with members of the orthomyxoviridae family although the viral glycoprotein appears to be related to gp64 of baculoviruses. characterization of tho virus was undertaken to clarify its taxonomic position. purified virus preparations contained at least six virus-encoded polypeptides with apparent m(r) values ranging from 29k to 92k. a 75k polypeptide was identified as an envelope-associated glycoprotein by tr ... | 1992 | 1279100 |
| saliva-activated transmission (sat) of thogoto virus: dynamics of sat factor activity in the salivary glands of rhipicephalus appendiculatus, amblyomma variegatum, and boophilus microplus ticks. | thogoto (tho) virus is transmitted from infected to uninfected ticks when co-feeding on uninfected guinea-pigs, even though the guinea-pigs do not develop a detectable viraemia. this form of non-viraemic transmission is potentiated by a factor(s) secreted by the saliva of ticks and hence has been termed saliva-activated transmission (sat). the synthesis of the sat factor by the salivary glands of three ixodid tick species was determined by placing uninfected nymphal ticks on guinea-pigs that wer ... | 1992 | 1326431 |
| saliva activated transmission (sat) of thogoto virus: relationship with vector potential of different haematophagous arthropods. | tick saliva (or salivary gland extract) potentiates the transmission of thogoto (tho) virus to uninfected ticks feeding on a non-viraemic guinea-pig. this phenomenon has been named saliva activated transmission (sat). to investigate the potential of different haematophagous arthropods to mediate sat, guinea-pigs were infested with uninfected r.appendiculatus neumann nymphs and inoculated with tho virus and salivary gland extract (sge) derived from a range of ixodid (metastriate and prostriate) o ... | 1992 | 1330087 |
| the glycoprotein of thogoto virus (a tick-borne orthomyxo-like virus) is related to the baculovirus glycoprotein gp64. | thogoto (tho) virus is a tick-transmitted virus which shares morphological and biochemical characteristics with members of the orthomyxoviridae. the genome of thogoto virus comprises six segments of single-stranded, negative sense rna. the complete nucleotide sequence of the fourth largest rna segment of tho virus has been determined from cdna analyses. this rna segment is 1574 nt long and has a coding capacity for a glycoprotein of 512 amino acids with a predicted molecular weight of 57,550 da. ... | 1992 | 1733105 |
| dhori virus induced lesions in mice. | dhori and thogoto viruses are till now the only recognized tick-borne orthomyxoviruses. like thogoto virus, also dhori is highly hepatotropic for laboratory mice; the lesions in several organs resemble those described for influenza virus. | 1990 | 1983186 |
| non-viraemic transmission of thogoto virus: vector efficiency of rhipicephalus appendiculatus and amblyomma variegatum. | previous studies have demonstrated that thogoto virus is transmitted from infected to uninfected ticks when co-feeding on uninfected guinea-pigs, even though the guinea-pigs do not develop a detectable viraemia. furthermore, tick to tick transmission is potentiated by factors associated with the salivary glands of ticks (saliva activated transmission). the vector efficiency of 2 ixodid tick species, rhipicephalus appendiculatus and amblyomma variegatum, for thogoto virus was assessed using this ... | 1990 | 2096521 |
| a comparative study of the infection thresholds of thogoto virus in rhipicephalus appendiculatus and amblyomma variegatum. | infection thresholds of thogoto virus in 2 ixodid tick species, rhipicephalus appendiculatus and amblyomma variegatum, were compared. thogoto virus has been isolated from naturally infected r. appendiculatus and a. variegatum in central africa, where both commonly parasitize the same hosts. no significant difference was found between the infection thresholds of thogoto virus in the 2 species. the percentage of nymphs of both species infected by feeding on viremic hamsters was directly correlated ... | 1990 | 2166447 |
| the effect of host resistance to tick infestation on the transmission of thogoto virus by ticks. | tick-borne virus transmission was examined using guinea-pigs and hamsters previously infested with ticks. guinea-pigs developed immunity to rhipicephalus appendiculatus after a single exposure to the ticks. nymphal and adult stages that fed on resistant guinea-pigs had increased mortality during feeding, and reduced engorged weights. egg production from female ticks fed on resistant hosts fell by at least 50%. guinea-pigs maintained high levels of immunity to tick infestation for at least 210 da ... | 1990 | 2345364 |
| anatomical basis of thogoto virus infection in bhk cell culture and in the ixodid tick vector, rhipicephalus appendiculatus. | infection by thogoto (tho) virus, a tick-borne virus related to the orthomyxoviruses, has been compared in vertebrate cell culture and in rhipicephalus appendiculatus ticks using infectivity titrations, immunofluorescence, and immune electron microscopy with colloidal gold markers to detect cell surface and intracellular antigens. morphogenesis of tho virus in cell culture was similar to that of influenza virus, with polymorphic virus particles budding at the plasma membrane. in the tick, tho vi ... | 1989 | 2543769 |
| the effect of virus-immune hosts on thogoto virus infection of the tick, rhipicephalus appendiculatus. | thogoto (tho) virus infections of rhipicephalus appendiculatus ticks were examined using tick hosts immune to the virus. in the first set of experiments, ticks were infected by feeding on viraemic hamsters. inter-stadial infection of tho virus was not affected when ticks ingested a virus-immune bloodmeal but there was an effect on persistence of the virus. the incidence of intra-stadial infection was reduced by at least 40% when nymphs partially fed on viraemic hamsters and completed their blood ... | 1989 | 2558460 |
| non-viraemic transmission of thogoto virus: influence of time and distance. | previous studies have demonstrated that thogoto virus is transmitted from infected to uninfected ticks when co-feeding on uninfected guinea-pigs, even though the guinea-pigs do not develop detectable viraemia. the dynamics of this 'non-viraemic transmission' were investigated. the percentage of nymphs (recipients) that acquired virus increased from zero, when co-feeding with infected adults (donors) for 3 d, to 80% for a co-feeding period of 5 d. no statistically significant difference was detec ... | 1989 | 2617637 |
| viral interference in the tick, rhipicephalus appendiculatus. i. interference to oral superinfection by thogoto virus. | interference between arboviruses in a naturally infected tick vector is reported for the first time. rhipicephalus appendiculatus nymphs were dually infected with thogoto (tho) virus, a tick-borne virus, similar to members of the family orthomyxoviridae. in the first series of experiments examining 'inter-stadial' interference, larvae were orally infected with a temperature-sensitive (ts) mutant, and after moulting the nymphs were superinfected with the wild-type (wt) virus. in the second series ... | 1989 | 2778441 |
| viral interference in the tick, rhipicephalus appendiculatus. ii. absence of interference with thogoto virus when the tick gut is by-passed by parenteral inoculation. | genetic reassortment of thogoto (tho) virus has been demonstrated in dually infected rhipicephalus appendiculatus ticks. however previous results showed that oral superinfection is inhibited by interference. to ascertain the site of tho viral interference, ticks were infected parenterally or orally with a temperature-sensitive (ts) mutant of tho virus. infected ticks were then challenged with wild-type (wt) tho virus via parenteral inoculation. intra-stadial superinfection was carried out by par ... | 1989 | 2778442 |
| pathological lesions in mice infected with thogoto virus, a tick-borne orthomyxovirus. | the rna structure of tick-borne thogoto virus was found very closely related to that of the orthomyxovividae family. pathological lesions in the lungs, liver and intestine of white mice inoculated with thogoto virus resemble to those described for influenza virus, however, an important differential characteristic is the high hepatotropism of thogoto virus. thogoto virus infection in the liver of mice seems suitable for the study of virus-induced necrotic lesions. | 1986 | 2876615 |
| reassortment of thogoto virus (a tick-borne influenza-like virus) in a vertebrate host. | reassortment is an important factor in the evolution of segmented genome viruses. for arthropod-borne viruses it is important to determine whether the vertebrate host acts as a site of reassortant virus formation since vertebrates often act as amplifying hosts. mutants of thogoto virus, a tick-borne orthomyxo-like virus, were shown to produce wild-type progeny in a dually infected permissive host (hamster), when hamsters were infected with two mutant viruses either by direct inoculation or by or ... | 1987 | 3553426 |
| a novel mode of arbovirus transmission involving a nonviremic host. | in nature, infected and uninfected arthropod vectors often feed together on an animal. in mimicking this scenario in the laboratory, uninfected vectors were found to acquire virus while cofeeding on the same host as infected vectors. however, the vertebrate host on which they fed did not develop detectable levels of virus in its blood. these observations were made with thogoto virus, an influenza-like virus of medical and veterinary significance. rhipicephalus appendiculatus ticks were used as t ... | 1987 | 3616608 |
| in vivo reassortment of thogoto virus (a tick-borne influenza-like virus) following oral infection of rhipicephalus appendiculatus ticks. | arboviruses with segmented genomes have the potential to reassort in both their vertebrate hosts and arthropod vectors. reassortment of thogoto virus, a tick-borne orthomyxo-like virus, has been demonstrated following dual infection of hamsters by temperature-sensitive mutants. to investigate whether similar events can occur in ticks, rhipicephalus appendiculatus larvae and nymphs were dually infected by interrupted feeding on viraemic hamsters. wild-type reassortant virus was isolated from the ... | 1987 | 3655743 |
| antigenic uniformity of topotype strains of thogoto virus from africa, europe, and asia. | prototype thogoto virus from kenya and thogoto virus isolates from portugal, italy, nigeria, central african republic, cameroon, and iran were cross-tested by hemagglutination inhibition and serum dilution plaque reduction neutralization. considering the broad geographic distribution of these strains, the antigenic differences seen appear to be essentially minor. this uniformity suggests that the distribution of thogoto virus is due to repeated introduction of virus from common sources and that ... | 1987 | 3688319 |
| experimental studies on the transmission cycle of thogoto virus, a candidate orthomyxovirus, in rhipicephalus appendiculatus. | thogoto (tho) virus, a candidate orthomyxovirus, replicated in and was transmitted by larvae, nymphs, and adults of the brown ear tick, rhipicephalus appendiculatus. larvae fed on viremic hamsters (10(7-8) pfu/ml blood) acquired an average of 10(2.5) pfu per tick. following engorgement the titer dropped to 10(1.9) pfu on day 2 but increased by day 6 to 10(3.3) pfu. virus survived transstadially in these ticks as demonstrated by the fact that, on day 10, newly moulted nymphs contained, on average ... | 1986 | 3789274 |
| [ecology of tick-borne arboviruses in the central african republic]. | ticks have been collected on cattle skins for seven consecutive years in bangui, berberati, bangassou and bouar. 150 strains of arboviruses have been isolated from the four following species: amblyomma variegatum: dugbe, jos, thogoto, crimean-congo hemorragic fever (cchf), yellow fever, bhanja and pétévo; boophilus annulatus: dugbe, jos and thogoto; b. decoloratus: dugbe, jos, thogoto and cchf; hyalomma nitidum: cchf. dugbe (112 isolated strains), jos (19 isolates) and thogoto (11 isolates) viru ... | 1985 | 4028317 |
| characterization of thogoto virus isolated from ticks (rhipicephalus bursa) in western sicily, italy. | | 1974 | 4473911 |
| isolation of thogoto virus from rhipicephalus bursa ticks in western sicily. | | 1972 | 4680821 |
| isolation of thogoto virus from ticks in portugal. | an agent pathogenic for mice was isolated from rhipicephalus sanguineus ticks collected from goats from vila vicosa , portugal. the virus was shown serologically to be closely related to or identical with thogoto virus, which had previously been isolated from ticks over a wide geographic area including sicily, the african continent, and iran. | 1984 | 6203388 |
| abortion in sheep caused by thogoto virus. | | 1984 | 6441339 |
| 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 ... | 1995 | 7483270 |
| 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 ... | 1995 | 7645224 |
| the interferon-induced mx protein of chickens lacks antiviral activity. | cdna sequencing revealed that chick mx protein consists of 705 amino acids. its 84 n-terminal amino acids show no significant sequence homology to other mx proteins. they are followed by 514 residues that include a tripartite gtp binding consensus motif. this region shows 50-70% sequence identity to mammalian and duck mx proteins. sequences near the c terminus, including a leucine zipper motif, are also conserved, whereas the intervening 19 amino acids lack sequence similarity. this unique seque ... | 1995 | 7648434 |
| 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 ... | 1995 | 7745744 |
| enhanced virus resistance of transgenic mice expressing the human mxa protein. | mxa is a gtpase that accumulates to high levels in the cytoplasm of interferon-treated human cells. expression of mxa cdna confers to transfected cell lines a high degree of resistance against several rna viruses, including influenza, measles, vesicular stomatitis, and thogoto viruses. we have now generated transgenic mice that express mxa cdna in the brain and other organs under the control of a constitutive promoter. embryonic fibroblasts derived from the transgenic mice were nonpermissive for ... | 1995 | 7769712 |
| 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 ... | 1995 | 7884909 |
| [a new look at transmission and circulation of tick encephalitis virus in nature]. | the author summarizes briefly the results of experiments which provide evidence of non-viraemic transmission of the virus from infected to non-infected ticks during co-feeding on a non-viraemic host. this mode of transmission originally found in the thogoto virus and its vector, the tick rhipicephalus appendiculatus, was proved also in the virus of tick-borne encephalitis and its vector ixodes ricinus. based on this fact some conclusions are drawn revising the accepted view regarding the life cy ... | 1994 | 7953087 |
| 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 ... | 1996 | 8970956 |
| 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 ... | 1996 | 8971034 |
| 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 ... | 1997 | 9060610 |
| 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 ... | 1997 | 9191867 |
| 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 ... | 1997 | 9282786 |
| 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 ... | 1997 | 9343188 |
| 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 ... | 1997 | 9343189 |
| 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 ... | 1998 | 9499090 |
| 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 ... | 1998 | 9519823 |
| tick virus diseases of sheep and goats. | tick-borne viruses affecting sheep and goats can be be locally important diseases. viruses of the tick-borne encephalitis complex occur across europe to north-east asia and are the cause of significant losses in small ruminant production. thogoto virus which can be transmitted by ixodid ticks has been associated with abortion storms in sheep, it may contribute to the large proportion of abortions which are due to unknown causes. nairobi sheep disease is the most pathogenic virus disease known fo ... | 1997 | 9530690 |
| 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 ... | 1998 | 9733885 |
| mxa gtpase: oligomerization and gtp-dependent interaction with viral rnp target structures. | mxa protein is an interferon-induced gtpase of human cells that inhibits the multiplication of several rna viruses, including influenza viruses and bunyaviruses. studies on mxa transgenic mice have shown that mxa is a powerful antiviral agent in vivo. it has been suggested that this cellular protein also protects humans from viral disease, but the mechanism(s) by which mxa exerts its antiviral action is still poorly understood. using an in vitro cosedimentation assay, we now demonstrate that mxa ... | 1998 | 9735310 |
| 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 ... | 1998 | 9770415 |
| 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 ... | 1998 | 9879758 |
| 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 ... | 1999 | 9933640 |
| 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 ... | 1999 | 10051598 |
| 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 ... | 1999 | 10400797 |
| 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 ... | 1999 | 10466973 |
| 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 ... | 1999 | 10486113 |
| 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 ... | 2000 | 10590150 |
| 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 ... | 2000 | 10773317 |
| 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 ... | 2000 | 10933733 |
| 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 ... | 2000 | 11044123 |
| 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 ... | 2000 | 11086115 |
| 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 ... | 2001 | 11315177 |
| 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 ... | 2001 | 11533190 |
| 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 ... | 2001 | 11576460 |
| [the influenza viruses: past, present and future]. | influeza disease is an underestimated public health problem. epidemics spread rapidly from country to country and may affect as many as 500 million people all over the world in a year. the disease, particularly influenza a may kill the patients and the new influenza viruses which appeared in 1957 (asian influenza) and 1968 (hong kong) are estimated to have caused at least 3 000 000 deaths in the world. there are several aspects in virus replication and maturation that have attracted considerable ... | 1996 | 11625150 |
| interferon-induced antiviral mx1 gtpase is associated with components of the sumo-1 system and promyelocytic leukemia protein nuclear bodies. | mx proteins are interferon-induced large gtpases, some of which have antiviral activity against a variety of viruses. the murine mx1 protein accumulates in the nucleus of interferon-treated cells and is active against members of the orthomyxoviridae family, such as the influenza viruses and thogoto virus. the mechanism by which mx1 exerts its antiviral action is still unclear, but an involvement of undefined nuclear factors has been postulated. using the yeast two-hybrid system, we identified ce ... | 2001 | 11716541 |
| 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 ... | 2001 | 11724276 |
| 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 ... | 2002 | 11992001 |
| 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) ... | 2001 | 12171274 |
| interferon-induced mx proteins: dynamin-like gtpases with antiviral activity. | mx proteins are interferon-induced gtpases that belong to the dynamin superfamily of large gtpases. similarities include a high molecular weight, a propensity to self-assemble, a relatively low affinity for gtp, and a high intrinsic rate of gtp hydrolysis. a unique property of mx gtpases is their antiviral activity against a wide range of rna viruses, including bunya- and orthomyxoviruses. the human mxa gtpase accumulates in the cytoplasm of interferon-treated cells, partly associating with the ... | 2002 | 12230469 |
| 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 ... | 2003 | 12552016 |
| two aromatic residues in the pb2 subunit of influenza a rna polymerase are crucial for cap binding. | mrnas are capped at their 5'-end by a unique cap structure containing n7-methyl guanine. recognition of the cap structure is of paramount importance in some of the most central processes of gene expression as well as in some viral processes, such as priming of influenza virus transcription. the recent resolution of the structure of three evolutionary unrelated cap binding proteins, the vaccinia viral protein vp39, the eukaryotic translation factor eif4e, and the nuclear cap-binding protein cbp20 ... | 2003 | 12646557 |
| 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 ... | 2003 | 12932755 |
| thogoto virus: a hitherto underscribed agent isolated from ticks in kenya. | | 1965 | 14329965 |
| 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 ... | 2004 | 15452266 |
| 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 ... | 2004 | 15557243 |
| 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 ... | 2005 | 15582653 |
| persistent gene expression in mouse nasal epithelia following feline immunodeficiency virus-based vector gene transfer. | gene transfer development for treatment or prevention of cystic fibrosis lung disease has been limited by the inability of vectors to efficiently and persistently transduce airway epithelia. influenza a is an enveloped virus with natural lung tropism; however, pseudotyping feline immunodeficiency virus (fiv)-based lentiviral vector with the hemagglutinin envelope protein proved unsuccessful. conversely, pseudotyping fiv with the envelope protein from influenza d (thogoto virus gp75) resulted in ... | 2005 | 16188984 |
| 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 ... | 2005 | 16354811 |
| interferon-induced mx proteins in antiviral host defense. | mx proteins are key components of the antiviral state induced by interferons in many species. they belong to the class of dynamin-like large guanosine triphosphatases (gtpases) known to be involved in intracellular vesicle trafficking and organelle homeostasis. mx gtpases share structural and functional properties with dynamin, such as self-assembly and association with intracellular membranes. a unique property of some mx gtpases is their antiviral activity against a wide range of rna viruses, ... | 2007 | 17570575 |
| 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 ... | 2008 | 18282283 |
| 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 ... | 2008 | 18768974 |
| 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 ... | 2010 | 19812269 |
| 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 ... | 2010 | 20808435 |
| 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 ... | 2010 | 20861272 |
| ticks: physiological aspects with implications for pathogen transmission. | ticks have attracted a great deal of scientific attention primarily because of their role as vectors of numerous pathogens. the majority of tick researchers worldwide focus primarily on microbiological and clinical issues relating to these pathogens, and on methods (pesticidal and biological) for controlling tick populations. unfortunately, it is often forgotten that ticks are also interesting in their own right to the general biologist because of their unusual physiological (and other) adaptati ... | 2010 | 21771507 |
| evolution-guided identification of antiviral specificity determinants in the broadly acting interferon-induced innate immunity factor mxa. | mxa is an interferon-induced dynamin-like gtpase with wide-ranging antiviral activity, which hinges upon detection of unique viral structures that differ across virus families. despite elucidation of its structure, the basis of mxa antiviral specificity remains enigmatic. we used an evolution-guided approach to identify the loop l4 of mxa as a hotspot for recurrent positive selection in primates. further, we show that single amino acid changes in l4 are necessary and sufficient to explain dramat ... | 0 | 23084925 |
| upolu virus and aransas bay virus, two presumptive bunyaviruses, are novel members of the family orthomyxoviridae. | emerging and zoonotic pathogens pose continuing threats to human health and ongoing challenges to diagnostics. as nucleic acid tests are playing increasingly prominent roles in diagnostics, the genetic characterization of molecularly uncharacterized agents is expected to significantly enhance detection and surveillance capabilities. we report the identification of two previously unrecognized members of the family orthomyxoviridae, which includes the influenza viruses and the tick-transmitted tho ... | 2014 | 24574415 |
| arboviruses pathogenic for domestic and wild animals. | the objective of this chapter is to provide an updated and concise systematic review on taxonomy, history, arthropod vectors, vertebrate hosts, animal disease, and geographic distribution of all arboviruses known to date to cause disease in homeotherm (endotherm) vertebrates, except those affecting exclusively man. fifty arboviruses pathogenic for animals have been documented worldwide, belonging to seven families: togaviridae (mosquito-borne eastern, western, and venezuelan equine encephaliliti ... | 2014 | 24751197 |
| ph-dependent conformational changes of a thogoto virus matrix protein reveal mechanisms of viral assembly and uncoating. | orthomyxoviruses are a family of ssrna virus, including influenza virus, infectious salmon anaemia virus and thogoto virus. the matrix proteins of orthomyxoviruses play crucial roles in some essential processes of the viral life cycle. however, the mechanisms of the matrix proteins involved in these processes remain incompletely understood. currently, only the structure and function of the matrix protein from influenza virus have been studied. here, we present the crystal structures of the n-ter ... | 2016 | 27411929 |
| influenza virus susceptibility of wild-derived cast/eij mice results from two amino acid changes in the mx1 restriction factor. | the interferon-regulated mx1 gene of the a2g mouse strain confers a high degree of resistance against influenza a and thogoto viruses. most other laboratory inbred mouse strains carry truncated nonfunctional mx1 alleles and, consequently, exhibit high virus susceptibility. interestingly, cast/eij mice, derived from wild mus musculus castaneus, possess a seemingly intact mx1 gene but are highly susceptible to influenza a virus challenge. to determine whether the enhanced influenza virus susceptib ... | 2016 | 27654285 |
| structural requirements for the antiviral activity of the human mxa protein against thogoto and influenza a virus. | the interferon-induced dynamin-like mxa protein has broad antiviral activity against many viruses, including orthomyxoviruses such as influenza a and thogoto virus and bunyaviruses such as la crosse virus. mxa consists of an n-terminal globular gtpase domain, a connecting bundle signaling element, and the c-terminal stalk that mediates oligomerization and antiviral specificity. we previously reported that the disordered loop l4 that protrudes from the compact stalk is a key determinant of antivi ... | 2014 | 24448803 |
| in vivo conditions enable ifnar-independent type i interferon production by peritoneal cd11b+ cells upon thogoto virus infection. | type i interferons (ifns) crucially contribute to host survival upon viral infections. robust expression of type i ifns (ifn-α/β) and induction of an antiviral state critically depend on amplification of the ifn signal via the type i ifn receptor (ifnar). a small amount of type i ifn produced early upon virus infection binds the ifnar and activates a self-enhancing positive feedback loop, resulting in induction of large, protective amounts of ifn-α. unexpectedly, we found robust, systemic ifn-α ... | 2016 | 27512061 |
| arbovirus and insect-specific virus discovery in kenya by novel six genera multiplex high-resolution melting analysis. | a broad diversity of arthropod-borne viruses (arboviruses) of global health concern are endemic to east africa, yet most surveillance efforts are limited to just a few key viral pathogens. additionally, estimates of arbovirus diversity in the tropics are likely to be underestimated as their discovery has lagged significantly over past decades due to limitations in fast and sensitive arbovirus identification methods. here, we developed a nearly pan-arbovirus detection assay that uses high-resolut ... | 2016 | 27482633 |
| isolation of the thogoto virus from a haemaphysalis longicornis in kyoto city, japan. | ticks transmit viruses responsible for severe emerging and re-emerging infectious diseases, some of which have a significant impact on public health. in japan, little is known about the distribution of tick-borne viruses. in this study, we collected and tested ticks to investigate the distribution of tick-borne arboviruses in kyoto, japan, and isolated the first thogoto virus (thov) to our knowledge from haemaphysalis longicornis in far-eastern asia. the japanese isolate was genetically distinct ... | 2015 | 25957096 |
| role of nucleotide binding and gtpase domain dimerization in dynamin-like myxovirus resistance protein a for gtpase activation and antiviral activity. | myxovirus resistance (mx) gtpases are induced by interferon and inhibit multiple viruses, including influenza and human immunodeficiency viruses. they have the characteristic domain architecture of dynamin-related proteins with an n-terminal gtpase (g) domain, a bundle signaling element, and a c-terminal stalk responsible for self-assembly and effector functions. human mxa (also called mx1) is expressed in the cytoplasm and is partly associated with membranes of the smooth endoplasmic reticulum. ... | 2015 | 25829498 |
| [research advances on thogoto virus of the family orthomyxoviridae]. | thogoto virus belongs to the family orthomyxoviridae. it is a tick-borne arbovirus that can infect both human and animals. thogoto virus's genetic constitution, replication and transcription, and the function of the translated proteins are similar to influenza virus. the studies on thogoto virus are important for us to better understand the conservative sites of influenza virus. moreover, the animal model of thogo-to virus is expected to be an alternative model for highly pathogenic influenza vi ... | 2013 | 24386846 |
| evolution and antiviral specificities of interferon-induced mx proteins of bats against ebola, influenza, and other rna viruses. | bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as ebola and influenza viruses. however, for unknown reasons, viral infections rarely cause clinical symptoms in bats. a tight control of viral replication by the host innate immune defense might contribute to this phenomenon. transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (mx) proteins in bats, but detailed functional aspects have not b ... | 2017 | 28490593 |