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prevalence of feline immunodeficiency virus and other retroviral infections in sick cats in italy.two hundred and seventy-seven sick pet cats living in italy were tested for antibodies to feline immunodeficiency virus (fiv) and for feline leukemia virus (felv) antigen. overall, 24% of the cats resulted positive for anti-fiv antibody and 18% for felv antigen. fiv was isolated from the peripheral mononuclear blood cells of ten out of 15 seropositive cats examined and from one out of eight saliva samples. no fiv isolations were obtained from six serum samples cultured. feline syncytium forming ...19921317073
human spumaretrovirus-related sequences in the dna of leukocytes from patients with graves disease.viruses, and more particularly retroviruses, have been postulated to play a role in the pathogenesis of autoimmune diseases. in a search for spumaretrovirus infection markers, we screened a group of 29 patients with graves disease and a representative healthy population (23 subjects) as a control. southern blot hybridization under stringent conditions, of patients' dna extracted from peripheral blood lymphocytes, with a spumaretrovirus-specific genomic probe derived from the human spumaretroviru ...19921332028
bovine respiratory syncytial virus fusion protein gene: sequence analysis of cdna and expression using a baculovirus vector.the nucleotide sequence of bovine respiratory syncytial virus (rsv), atcc strain a51908 fusion (f) glycoprotein gene cdna was determined. the amino acid sequence deduced was then compared to those of two different isolates of bovine rsv, strains rb 94 and 391-2, and the a and b subtypes of human rsv, strains 18537 and a2. the bovine rsv f protein is highly conserved between the three isolates, a51908 has 97% amino acid identity to rb 94, and 99% identity to 391-2. the f proteins of both the a an ...19921318950
bacterial expression of the capsid antigen domain and identification of native gag proteins in spumavirus-infected cells.a bacterial expression plasmid containing the central part of the gag gene of the human spumaretrovirus (hsrv) was constructed and expressed in e. coli. the expected protein product consisting of the complete region of the hsrv capsid antigen and part of the matrix protein was expressed in relatively large amounts. polyclonal antisera raised against this recombinant protein were used to identify authentic gag precursors of 78 and 74 kda and processed gag proteins of 60, 58, and 33 kda in hsrv-in ...19921318626
no evidence of spumaretrovirus infection markers in 19 cases of de quervain's thyroiditis. 19921333778
mo-mulv nucleotide sequence exhibits three levels of oligomeric repetitions, suggesting a stepwise molecular evolution.an exhaustive computer-assisted analysis of the moloney murine leukemia virus nucleotide sequence shows numerous deviations in the oligomeric distribution, suggesting three overlapping levels of a stepwise duplicative evolution. (1) the sequence fits the universal rule of tg/ct excess which has been proposed as the construction principle of all sequences, and maintains some degree of symmetry between the two complementary strands. (2) oligomeric repeating units share a core consensus regularly s ...19921336800
no evidence for spumavirus or oncovirus infection in relapsing-remitting multiple sclerosis.polymerase chain reaction analysis was used to investigate the possible role of human spumaretrovirus and oncoretroviruses (human t-cell lymphotropic virus types i [htlv-i] and ii [htlv-ii]) in multiple sclerosis. eleven patients with relapsing-remitting multiple sclerosis in exacerbation and 11 normal blood donors were included in the study. cerebrospinal fluid cells, peripheral blood mononuclear cells, and plasma were cocultured with allogeneic mononuclear cells for 6 weeks. cultured cells wer ...19921333176
[basic understanding of retroviruses].retroviruses contain a reverse transcriptase in the virion that converts viral genomic rna to proviral dna. retroviruses are divided into three groups; oncovirus, lentivirus, and spumavirus. the oncovirus group contains htlv-1, which causes adult t-cell leukemia, encephalomyeloneuropathy, arthritis, and alveolo-bronchopathy. the lentivirus groups contains hiv, which causes acquired immunodeficiency syndrome and dementia. the genomic structures and functions of htlv-1 and hiv have been demonstrat ...19921630036
genomic organization and expression of simian foamy virus type 3 (sfv-3).the complete nucleotide sequence of simian foamy virus type 3 (sfv-3) strain lk-3, isolated from an african green monkey, was determined. in addition to translation frames representing the gag, pol, and env genes, two open reading frames are located in the region between the env gene and the 3' long terminal repeat (ltr). both sfv-3 and sfv-1 encode two open reading frames between env and the 3' ltr, whereas hfv encodes three open reading frames in this region. northern blot analysis of cell cul ...19921310187
sequence analysis of m2 mrna of bovine respiratory syncytial virus obtained from an f-m2 dicistronic mrna suggests structural homology with that of human respiratory syncytial virus.the nucleotide sequences of the f and m2 mrnas of strain a51908 of bovine respiratory syncytial virus (brsv) were determined by sequencing cdna of an intracellular dicistronic mrna. comparison of the f mrna sequence with those of other brsv strains showed that there was extensive sequence identity at both the nucleotide (95% identity) and amino acid (94% identity) levels. alignment of the nucleotide and encoded amino acid sequences of m2 mrna of brsv with those of human respiratory syncytial vir ...19921312130
absence of antibody to human spumaretrovirus in patients with chronic fatigue syndrome. 19921313314
human spumavirus antibodies in sera from african patients.serum samples collected from patients with a wide variety of diseases from african and other countries were tested for antibodies to the human spumaretrovirus (hsrv). a spumaviral env-specific elisa was employed as screening test. out of 3020 human sera screened, 106 were found to be positive (3.2%). while the majority of patients' sera from europe (1581) were negative, 26 were positive (1.6%). sera from healthy adult blood donors (609), from patients with multiple sclerosis (48), graves' diseas ...19921314048
isolation of a spumavirus from a sheep. 19921320857
generation of macaque b lymphoblastoid cell lines with simian epstein-barr-like viruses: transformation procedure, characterization of the cell lines and occurrence of simian foamy virus.two simian epstein-barr-like viruses, a rhesus epstein-barr virus and herpesvirus papio, were used to transform b cells from rhesus or cynomolgus macaques. the resulting cell lines exhibited predominantly a b lymphocyte phenotype and expressed epstein-barr virus antigens. the majority of b lymphoblastoid cell lines from macaques, which were seropositive for simian foamy virus, developed giant cells in culture. the cytopathic agent was identified as a foamy virus and was transmissible to human em ...19921331148
bovine immunodeficiency-like virus encodes factors which trans activate the long terminal repeat.lentiviruses are known to encode factors which trans activate expression from the viral long terminal repeat (ltr); the primary trans activator is the tat gene product. one of the putative accessory genes (tat) of the bovine immunodeficiency-like virus (biv) bears sequence similarity to other lentivirus tat genes. this finding suggests that biv may encode a trans-activating protein capable of stimulating ltr-directed gene expression. to test this hypothesis in vitro, biv ltr-chloramphenicol acet ...19921313891
expression of human foamy virus is differentially regulated during development in transgenic mice.the human foamy virus (hfv) is a recently characterized member of the spumavirus family. although no diseases have been unequivocally associated with hfv infection, expression of hfv regulatory genes in transgenic mice induces a characteristic acute neurodegenerative disease and a myopathy. to better characterize the sequence of events leading to disease, and to gain a better understanding of the underlying pathogenetic mechanisms, we have analyzed in detail the transgene expression pattern duri ...19921316144
transactivation of human immunodeficiency virus type 1 long terminal repeat-directed gene expression by the human foamy virus bel1 protein requires a specific dna sequence.human foamy virus (hfv) encodes the transcriptional transactivator bel1. the bel1 protein transactivates hfv long terminal repeat (ltr)-directed gene expression by recognizing a region in u3. it also transactivates human immunodeficiency virus type 1 (hiv-1) ltr-directed gene expression in transient transfection assays. to identify the specific region in hiv-1 ltr responsible for bel1 action, we examined the effect of bel1 on chloramphenicol acetyltransferase (cat) gene expression in transfected ...19921313928
the bel-1 protein of human foamy virus activates human immunodeficiency virus type 1 gene expression via a novel dna target site.the bel-1 protein of human foamy virus can activate transcription directed by the long terminal repeat (ltr) promoter of human immunodeficiency virus type 1 (hiv-1). the target sequence for bel-1 is shown to lie within the hiv-1 ltr u3 region but does not coincide with any previously described factor-binding site. gene expression directed by an hiv-1 ltr lacking functional sites for the inducible cellular transcription factor nf-kappa b was activated over 100-fold by coexpression of bel-1. these ...19921316494
cis-acting regulatory regions in the long terminal repeat of simian foamy virus type 1.simian foamy virus type 1 (sfv-1), a member of the spumavirinae subfamily of retroviruses, encodes a transcriptional transactivator (taf) that strongly augments gene expression directed by the viral long terminal repeat (ltr) (a. mergia, k. e. s. shaw, e. pratt-lowe, p. a. barry, and p. a. luciw, j. virol. 65:2903-2909, 1991). this report describes cis-acting regulatory elements in the ltr that control viral gene expression. a series of ltr mutants and hybrid promoter constructs have been analyz ...19921309244
human foamy virus: an underestimated neuropathogen?human foamy virus (hfv) is a recently characterized retrovirus which was originally isolated from patients with various neoplastic and degenerative diseases. however, until today it has not been possible to identify hfv as the causative agent of any disease and little is known about its prevalence in human populations. like htlv and hiv, hfv encodes the three structural retroviral genes, gag, pol and env, and an additional region containing three open reading frames, bel-1 to bel-3. bel-1 activa ...19921341948
human foamy virus antigens in thyroid tissue of graves' disease patients.human foamy virus (hfv) is a recently characterized member of the retrovirus subfamily spumaretrovirinae. hfv has a complex structure: it encodes the classical three retroviral structural genes gag, pol and env, but also possesses additional regulatory, so-called bel sequences. foamy viruses have been discussed occasionally as being possibly involved in the pathogenesis of autoimmune thyroiditis. by indirect immunofluorescence we were able to demonstrate the expression of hfv gag proteins on the ...19921336420
a defective human foamy provirus generated by pregenome splicing.foamy viruses are a group of retroviruses of complex structure which were thought to be non-pathogenic. the recent demonstration of neurological diseases in mice transgenic for human foamy virus (hfv) and the high prevalence of hfv sequences in graves' disease question this idea. by pcr, we have detected hfv sequences with a non-random deletion in the bel1 transactivator gene in other autoimmune conditions. sequence analysis revealed that this deleted area corresponds to the excision of a known ...19938223453
expression of the human foamy virus bel-1 transactivator in insect cells.the human foamy virus (hfv) bel-1 transactivator protein was expressed in insect cells by a recombinant baculovirus. for the generation of the recombinant baculovirus, acbel-1, the bel-1 gene of an hfv mutant was used, that bears truncations in the bel-1 overlapping bel-2 open reading frame. acbel-1 infected sf9 cells produced high amounts of recombinant protein of the same electrophoretic mobility (36 kd) as bel-1 expressed in mammalian cells. the baculovirus expressed bel-1 protein was readily ...19938266722
simian foamy virus type 3 (sfv-3) in latently infected vero cells: reactivation by demethylation of proviral dna.cell cultures latently infected with simian foamy virus type 3 (sfv-3) were established by suppressing lytic infection in vero cells with 3'-azido-3'-deoxythymidine (azt) and homologous antibodies (african green monkey serum immune to sfv-3). the resulting cell line, designated vero-l, was shown to contain at least one copy per cell of sfv-3 dna stably integrated at a defined site of the host cell genome. sequencing of 669 bp at the integration site did not identify a coding region and revealed ...19938380669
functional organization of the bel-1 trans activator of human foamy virus.human foamy virus encodes a 300-amino-acid nuclear regulatory protein termed bel-1 that is required for human foamy virus replication in culture. bel-1 is a potent trans-activator of gene expression directed by the homologous hfv long terminal repeat as well as the long terminal repeat of human immunodeficiency virus type 1. we have used mutational analysis to define several discrete functional domains within bel-1. the c-terminal approximately 50 amino acids of bel-1 are shown to be essential f ...19938383217
endonucleolytic cleavages and dna-joining activities of the integration protein of human foamy virus.the bacterial expression plasmids, pet3b and pet16b, that contain the integrase domain of the human foamy virus (hfv) reverse transcriptase were constructed and expressed in escherichia coli. the histidine-tagged hfv in protein was purified to near homogeneity by single-step ni2+ chelate affinity chromatography. hfv-specific proteins of 39 and 120 kda from virus-infected cells reacted with antisera raised against the recombinant in protein. purified recombinant hfv in protein was active as an en ...19937688824
retrovirus infections of the nervous system.mammalian retroviruses of all three subfamilies infect the nervous system. the leukemia viruses (oncovirinae) and lentiviruses (lentivirinae, eg, human immunodeficiency virus) cause serious disease, while the foamy viruses (spumavirinae) have not yet been shown to cause any disease. this review illustrates these diseases by referring particularly to three viruses: the human and murine leukemia viruses (human t-cell leukemia-lymphoma virus type i and murine leukemia virus), and the human immunode ...19938386955
identification of pol-related gene products of human foamy virus.human foamy virus pol gene fragments were molecularly cloned into a procaryotic expression vector. the expression pattern of the cloned fragments and nucleotide sequence analysis of the 5' pol gene region revealed that in hfv the protease (pr) is located in the pol open reading frame. purified recombinant proteins were used to generate antibodies in rats. in immunoblot assay, using infected cells as antigen, a precursor protein with an apparent molecular mass (m(r)) of 127k was identified by ant ...19938390761
regulatory elements in the long terminal repeat (ltr) of simian foamy virus type 3 (sfv-3).simian foamy virus type 3 (sfv-3) is a retrovirus that has a complex genome organization and encodes two open reading frames (orf-1 and orf-2) in addition to the genes coding for gag, pol, and env. in this report, we demonstrate that orf-1 of sfv-3 encodes a transcriptional transactivator designated taf (transactivator of foamy virus) which augments gene expression directed by the viral long terminal repeat (ltr). the taf responsive elements have been mapped to the u3 region of the ltr, between ...19938390763
evaluation of cofactor effect of feline syncytium-forming virus on feline immunodeficiency virus infection.although feline immunodeficiency virus (fiv) and the unrelated retrovirus feline leukemia virus (felv) are associated with acquired immune deficiency in cats, experimental and field evidence indicates that coinfection with both viruses may lead to more serious disease syndrome. a third feline retrovirus, feline syncytium-forming virus (fesfv), which is far more prevalent than either fiv or felv and is considered nonpathogenic in nature, is consistently coisolated from sick, fiv-infected cats. to ...19938391229
functional domains of the simian foamy virus type 1 transcriptional transactivator (taf).the genome of simian foamy virus type 1 encodes a transcriptional transactivator (taf) that dramatically elevates gene expression directed by the viral long terminal repeat. in this report, we describe the functional domains of simian foamy virus type 1 taf. several taf mutants and fusion proteins of taf and the dna-binding domain of the saccharomyces cerevisiae transcriptional transactivator gal4 were used in this study. taf contains two potent activation domains. one of the activation domains ...19938392601
[amyotrophic lateral sclerosis--indications of increased antiretroviral seroreactivity without obvious epidemiology].of 25 male and 13 female patients diagnosed as sporadic cases of amyotrophic lateral sclerosis between 1989 and 1992, 17 had reproducible serum antibodies against human foamy virus (hfv = human spuma retrovirus, hsrv). hfv-positive als patients had higher igg3 concentrations than hfv-negatives (p < 0.05) and competed better on maedi-visna retroviral antigen than hfv-negatives or controls (p < 0.05), but did not differ otherwise. two hfv-positive patients were living in the same building; two oth ...19938392664
inability of retroviral tests to identify persons with chronic fatigue syndrome, 1992.chronic fatigue syndrome (cfs) is characterized by prolonged, debilitating fatigue. although the cause of cfs unknown, cdc and researchers in other organizations have been investigating whether infection with a previously unidentified retrovirus might be an etiologic factor. based on reports suggesting that retroviral infection with a human t-lymphotropic virus type 2 (htlv-ii)-like retrovirus or a spumavirus might be associated with cfs, some research and commercial laboratories developed assay ...19938446093
amyotrophic lateral sclerosis an enigmatic disease with b-cellular and anti-retroviral immune responses.the most frequent sporadic adult motor neuron disease, amyotrophic lateral sclerosis, affects more men, follows no epidemiologic pattern, and was long considered a pure spinal cord disorder. it now becomes evident that the disease is characterized by spinal, cerebral and extra-neuromuscular changes including b-cellular responses and ultrastructural skin alterations. do these parameters identify subgroups or correlate with the male preponderance of the disease?19938252177
transient immunosuppressive effect induced in rabbits and mice by the human spumaretrovirus prototype hfv (human foamy virus).spumaviruses (foamy viruses) constitute one of the three retroviral genera isolated from man. although spumaviruses have not been clearly linked to a given pathology in humans and other infected species, it is well established that they lead in vivo to chronic infections without detectable viral expression. we thought it of interest to investigate certain aspects of the pathology induced in laboratory animals by human foamy virus (hfv). in this work, we demonstrate that hfv infection of rabbits ...19938284516
transcriptional trans activators of human and simian foamy viruses contain a small, highly conserved activation domain.the bel-1 protein of human foamy virus is a potent transcriptional trans activator of its homologous long terminal repeat promoter element. here, we demonstrate that bel-1 can also efficiently activate gene expression when targeted to a heterologous promoter by fusion to the dna-binding motif of the yeast gal4 protein. analysis of a series of deletion mutants of bel-1 generated in this hybrid protein context suggests the presence of a single transcription activation domain that is fully containe ...19938411385
functional dissection of the human spumaretrovirus transactivator identifies distinct classes of dominant-negative mutants.the bel1 gene of human spumaretrovirus (hsrv) codes for a 300-amino-acid nuclear protein, termed bel1, that can strongly activate transcription from the cognate long terminal repeat (ltr) by at least 200-fold. bel1 can also activate human immunodeficiency virus type 1 (hiv-1) ltr expression. by using site-directed mutagenesis, we have identified distinct regions of bel1 essential for hsrv ltr activation. the amino-terminal 55 residues, which comprise a highly acidic region followed by a short ba ...19938380068
human spumaretrovirus in the etiology of sudden hearing loss.the etiology of sudden sensorineural hearing loss, so called sudden deafness, has for long puzzled researchers. recently we have studied the possibility that a hitherto relatively unknown retrovirus group consisting of human spumaretroviridae (hsrv) might be the causative agent of sudden deafness. during the last 3 months we have screened about 30 cases of sudden deafness. in 4 of them antibodies against hsrv were detected. three of them had suffered from a flu-like condition about 2 weeks befor ...19938382898
multiple positive and negative cis-acting elements that mediate transactivation by bel1 in the long terminal repeat of human foamy virus.the bel1 protein of human foamy virus (hfv), a retrovirus, regulates expression of the gene linked to the hfv long terminal repeat (ltr) and is essential for viral gene expression. the mechanism of action of the bel1 protein is unknown, but its action is mediated through the u3 region of the ltr. to determine which u3 sequences are critical for transactivation by bel1, a series of hybrid vectors consisting of a mutant hfv ltr and the chloramphenicol acetyltransferase gene were constructed and te ...19938383244
human foamy virus proteins accumulate in neurons and induce multinucleated giant cells in the brain of transgenic mice.human foamy virus (hfv) is a retrovirus encoding structural genes and, like human immunodeficiency virus and human t cell leukemia virus i, several ancillary reading frames collectively termed the be1 genes. we have previously shown that hfv transgenic mice develop an encephalopathy with neuronal loss in hippocampus and cerebral cortex. we have now raised and characterized rabbit antisera to various recombinant portions of gag, pol, env, and bel-1, the viral trans-activator. immunoreactivity for ...19938386440
human foamy virus polypeptides: identification of env and bel gene products.human foamy virus (hfv) proteins were identified in human cells cultured in vitro by immunoprecipitation and immunoblotting with specific antisera. among several viral polypeptides, four glycoproteins of approximately 160, 130, 70, and 48 kda were identified in hfv-infected cells. gp130 was shown to represent the intracellular env precursor, and gp70 and gp48 were shown to represent the external and transmembrane env proteins, respectively. the nature of gp160, which shares sequences with the en ...19938388512
the foamy virus family: molecular biology, epidemiology and neuropathology.the family of foamy viruses designates a group of retroviruses which share a specific morphology and provoke characteristic cytopathic effects in cultured cells. like htlv and hiv, foamy viruses are complex viruses encoding a number of ancillary genes in addition to gag, pol and env, including a transcriptional transactivator. foamy viruses are endemic in various primate species, and human foamy viruses (hfv) have been isolated from patients with various neoplastic and degenerative diseases. des ...19938389200
the carboxy-terminal transcription enhancement region of the human spumaretrovirus transactivator contains discrete determinants of the activator function.the bel1 gene of human spumaretrovirus (hsrv) encodes a 300-amino-acid nuclear protein termed bel1 that is a potent activator of transcription from the cognate long terminal repeat (ltr). bel1 can also efficiently activate the human immunodeficiency virus type 1 (hiv-1) ltr. we have previously shown that the amino-terminal 227-residue region (minimal activator region) of bel1 can activate the hsrv ltr at low levels and that two distinct domains within the carboxy-terminal 73 residues, from resid ...19938389909
investigation of retroviral involvement in chronic fatigue syndrome.within the last few years significant efforts have been made to identify objective reliable diagnostic markers from individuals with chronic fatigue syndrome (cfs). we report the absence of a previously described retroviral marker (htlv-ii gag) in a blinded study of cfs cases. even with excellent reproducible sensitivities, this marker failed in repeated attempts to distinguish cases from controls. in addition, four other retroviruses (simian t cell leukaemia virus, human spumavirus, bovine leuk ...19938387909
retroviral interference with neuronotrophic signaling in human motor neuron disease?we tested 13/32 patients with non-familial amyotrophic lateral sclerosis (als) positive (41%) for human spuma retrovirus (hsrv) seroreactivity. half the non-als hsrv-positive neurologic patients (12/25) reported multiple fasciculations within the last two years. sera from four hsrv-env negative als patients measurably competed with visna antibodies on maedi-visna antigen. the serologies for bovine leukemia virus, borna disease virus and gm1igm-antibodies remained negative. both visna and foamy v ...19938393394
human foamy virus genome possesses an internal, bel-1-dependent and functional promoter.the human foamy or spumaretrovirus (hsrv) is a complex retrovirus that encodes the three retroviral genes gag, pol, and env and, in addition, at least three bel genes. the hsrv bel-1 protein was identified as a transcriptional trans-activator. hsrv transcription starts in the 5' long terminal repeat at a defined guanine residue. we report here that a second efficiently utilized start site of transcription is contained within a hsrv env dna sequence upstream of the bel genes. bel-specific transcr ...19938394017
antiretroviral therapy in sporadic adult amyotrophic lateral sclerosis.clinical and experimental findings in idiopathic amyothrophic lateral sclerosis (als) would be compatible with a retroviral involvement. in 35 adult patients with non-familial als we observed elevated circulating immune complexes, a decrease in igg3 isotype and enzyme-linked sorbent assay (elisa) serum antibodies against human spuma retrovirus (hsrv), confirmed by specific human foamy virus immunoblots. all 35 were negative for igm or relevant igg anti-ganglioside antibodies. we treated 12 hiv-n ...19938394159
functional analysis of human foamy virus accessory reading frames.foamy viruses belong to the retroviruses which possess a complex genome structure. the human foamy virus (hfv) isolate bears three open reading frames (the so-called bel genes) in the 3' region of the genome which have been reported to give rise to possibly six different proteins via alternative splicing (w. muranyi and r. m. flügel, j. virol. 65:727-735, 1991). in order to analyze the requirements of these proteins for hfv replication in vitro, we constructed a set of single and combinatory bel ...19938394455
possible role of human foamy virus in graves' disease.human foamy virus (hfv) is a member of the retroviral family of spumaretrovirinae. in addition to the three retroviral structural genes, gag, pol and env, hfv also contains regulatory sequences, called bel. foamy viruses have been previously associated with human thyroid disease, notably dequervain's thyroiditis. in indirect immunofluorescence tests we have demonstrated the reactivity of the thyroid glands of 7/7 patients with graves' disease and antibodies to hfv gag proteins. no reactivity was ...19938407236
foamy viruses.foamy viruses share complex genome organization with lentiviruses and certain oncoviruses. the open reading frame 3' of env encodes a transcriptional transactivator. distinct responsive sequences were identified in the long terminal repeats (ltrs) of simian (sfv-1 and sfv-3) and human foamy viruses (hfv). transactivation of heterologous ltrs was described including those of simian and human immunodeficiency viruses. foamy viruses persist for the whole lifetime in infected hosts (primates, cats, ...19938407246
analysis of the role of the bel and bet open reading frames of human foamy virus by using a new quantitative assay.we have constructed a bhk-21-derived indicator cell line containing a single integrated copy of the beta-galactosidase (beta-gal) gene under control of the human foamy virus (hfv) long terminal repeat promoter (from -533 to +20). these foamy virus-activated beta-gal expression (fab) cells can be used in a quantitative assay to measure the infectious titer of hfv. our results show that the fab assay is 50 times more sensitive than determination of the virus titer by the end-point dilution method. ...19938411364
increase in the basal transcriptional activity of the human foamy virus internal promoter by the homologous long terminal repeat promoter in cis.the human foamy or spumaretrovirus hfv is a complex and exogenous retrovirus that encodes several bel genes besides the three classical retroviral genes gag, pol, and env. hfv was recently reported to contain two functionally active promoters that are both strongly trans-activated by the hfv trans-activator protein bel 1. the occurrence of a second internal cap site underscores the complexity of the hfv genome. we have analysed whether there is interference between the hfv long terminal repeat p ...19938414976
identification of human endogenous retroviruses with complex mrna expression and particle formation.retroviruses comprise strains with considerable disease potential in animals and humans. in addition to exogenous strains transmitted horizontally, endogenous proviruses are transmitted through the germ line. some of these endogenous retroviruses can be pathogenic in mice and possibly in other animal species. they may also be considered as mobile genetic elements with the potential to produce mutations. in humans, genomic dna contains numerous endogenous retroviral sequences detected by their pa ...19938506289
the bel1 protein of human foamy virus contains one positive and two negative control regions which regulate a distinct activation domain of 30 amino acids.the bel1 transactivator is essential for the replication of human foamy virus (hfv). to define the functional domains of hfv bel1, we generated random missense mutations throughout the entire coding sequence of bel1. functional analyses of 24 missense mutations have revealed the presence of at least two functional domains in bel1. one domain corresponds to a basic amino acid-rich motif which acts as a bipartite nuclear targeting sequence. a second, central domain corresponds to a presumed effect ...19948139046
transcriptional mapping of the 3' end of the bovine syncytial virus genome.the bovine syncytial virus, a member of the retroviral subfamily spumavirinae, causes a persistent, asymptomatic infection in cattle. nucleotide sequence analysis of the viral genome revealed two overlapping reading frames in the 3' region, traditionally occupied by accessory-function genes in other complex retroviruses. in order to analyze the transcripts from the accessory-gene region, we designed oligonucleotide primers complementary to sequences within the 5' and 3' long terminal repeats (lt ...19948289332
analysis of the 5' long terminal repeat of bovine syncytial virus.four molecular clones of the bovine syncytial virus (bsv) were determined to be replication competent by the initiation of cytopathic infections and production of viable virus following transfection of viral dna into permissive cells. the nucleotide (nt) sequence of the 5' long terminal repeat (ltr) of the infectious clone, bsv-11, was determined and analyzed to identify regions common to retroviral ltrs and elements with the potential for involvement in transcriptional regulation.19948163193
genetic analysis indicates that the human foamy virus bel-1 protein contains a transcription activation domain of the acidic class.human foamy virus encodes a nuclear regulatory protein, termed bel-1, that serves as a potent activator of viral transcription. mutational analysis has identified a small, discrete activation domain within bel-1 that is highly active in both higher and lower eukaryotic cells. here, we demonstrate that the activation domain of bel-1 is highly dependent on the ada2 transcriptional adaptor for biological activity in yeast cells, a property previously shown to be a hallmark of the vp16 class of acid ...19948189518
human spumaretrovirus antibody reactivity in multiple sclerosis.the role of human spumaretrovirus (hsrv) infections in the pathogenesis of multiple sclerosis (ms) was investigated with recombinant hsrv env-specific enzyme-linked immunosorbent assay. the presence of hsrv antibodies was determined in pairs of serum and cerebrospinal fluid (csf) samples from 60 ms patients. in 7 of these patients serial serum and csf samples were obtained in relation to the clinical activity of the disease during a period of 2 years. no increased antibody reactivity was demonst ...19948195818
absence of evidence for infection with the human spuma retrovirus in an outbreak of menière-like vertiginous illness in wyoming, usa. 19948203206
human spumaretrovirus in the etiology of sudden hearing loss. 19948203207
simian foamy virus type 1 contains a second promoter located at the 3' end of the env gene.simian foamy virus type 1 (sfv-1) is a member of a distinct subfamily of retroviruses that possess a complex genome organization as well as complex means of regulating gene expression. this virus encodes a transcriptional transactivator (taf) that dramatically increases gene expression directed by the viral long terminal repeat. in this report, the identification of a second promoter which is significantly transactivated by sfv-1 taf is described. the second promoter is located at the 3' end of ...19948116246
human foamy virus infection in myasthenia gravis. 19947906819
[neurotoxicity of human foamy virus in transgenic mice].human foamy virus (hfv) is a human retrovirus originally isolated from patients with various neoplastic and degenerative diseases. similarly to other human retroviruses, hfv encodes the three structural retroviral genes, gag, pol and env, and an additional region containing three open reading frames, bel-1 to bel-3. bel-1 activates transcription of the long terminal repeat of hfv and also of hiv. until today it has not been possible to identify hfv as the causative agent of any disease. in order ...19947533983
the gene expression of human foamy virus does not require a post-transcriptional transactivator.human foamy virus (hfv) comprises a complex genomic organization of gag, pol, env, and several nonstructural genes such as bel1, bel2, bel3, bet, beo, and bes located between env and 3' ltr. among these viral nonstructural genes, bel1 appears to encode an essential transactivator of ltr-directed gene expression. to investigate the roles of the other nonstructural proteins for the viral replication, a series of proviral mutants were generated and tested for their in vitro replication. the mutatio ...19947522374
the human foamy virus internal promoter directs the expression of the functional bel 1 transactivator and bet protein early after infection.the human foamy virus or spumaretrovirus (hfv) is a complex retrovirus that has the capacity to code not only for the three retroviral genes gag, pol, and env but, in addition, for at least three bel genes. the hfv provirus contains two different and functionally active promoters: the classical retroviral promoter in the 5' long terminal repeat and a recently identified second promoter in the env gene upstream of the bel genes. both promoter/enhancers are strongly dependent on the hfv transcript ...19948289367
evidence for superantigen activity of the bel 3 protein of the human foamy virus.the human foamy virus is a complex retrovirus that codes for several regulatory bel genes in addition to the conventional gag, pol, and env genes. the bel 3 gene is located in the 3' part of the viral genome comparable to that of the superantigen of the mouse mammary tumor virus. superantigens bound to major histocompatibility complex (mhc) class ii molecules have been shown to stimulate t cells in a v beta-specific manner. the recombinant bel 3 protein purified to near homogeneity was assayed i ...19947528260
isolation, cloning, and sequencing of simian foamy viruses from chimpanzees (sfvcpz): high homology to human foamy virus (hfv).several independent isolates of simian foamy viruses (sfv) were recovered from chimpanzee b-cell lines. one isolate, designated sfvcpz, was molecularly cloned and sequenced. in addition, the genome of sfv type 6 (sfv-6), an independent chimpanzee foamy virus isolate, was partially cloned. the sfvcpz provirus is 13,246 base pairs (bp) long. it is flanked by long terminal repeats (ltrs) and encodes the genes gag, pol, env, the transcriptional transactivator taf, and a second 3' open reading frame ...19948184531
nuclear localization of foamy virus gag precursor protein.all foamy viruses give rise to a strong nuclear staining when infected cells are reacted with sera from infected hosts. this nuclear fluorescence distinguishes foamy viruses from all other retroviruses. the experiments reported here indicate that the foamy virus gag precursor protein is transiently located in the nuclei of infected cells and this is the likely reason for the typical foamy virus nuclear fluorescence. by using the vaccinia virus expression system, a conserved basic sequence motif ...19948035493
differential effects of ras and jun family members on complex retrovirus promoter activities.infection by complex retroviruses such as visna-maedi, hiv1, htlv-i and hfv is generally not followed by particle production, but rather by a more or less prolonged latency period. knowledge of the mechanisms triggering an infectious cycle from the latent provirus(es) is of great importance in comprehending the appearance of the disease. it is currently admitted that cellular factors regulate viral expression. in this paper, we report the ability of ras, c-jun, jun-b and jun-d to diversely stimu ...19947709072
reactivity of primate sera to foamy virus gag and bet proteins.in order to establish criteria for the serodiagnosis of foamy virus infections we investigated the extent to which sera from infected individuals of human and primate origin react with structural and non-structural virus proteins in immunoblot assays. using lysates from infected cells as the source of virus antigen, antibodies were preferentially detected against the gag proteins and the non-structural bet protein. both the gag precursor molecules of 70 and 74k apparent m(r) and the cytoplasmic ...19947931149
isolation of a new foamy retrovirus from orangutans.we have isolated a new foamy virus from blood samples taken from two apparently healthy orangutans (pongo pygmaeus). the older orangutan has since died with encephalopathy after a brief acute illness, while the younger one, his grandson, remains well. these animals and 12 other orangutans had specific antibodies to foamy virus as measured by immunofluorescence. the new foamy virus and the antisera showed strong and specific neutralization, with only weak cross-reaction with other simian foamy vi ...19947933094
structure and function of the long terminal repeat of the chimpanzee foamy virus isolates (sfv-6).the complete long terminal repeat (ltr) nucleotide sequence of the chimpanzee foamy virus isolate sfv-6 was determined. its 1761-bp size makes it the longest ltr reported to date among all retroviruses. since the length of its ltr is similar to that of other simian isolates while its sequence homology is closer to that of hfv, sfv-6 genetic structure appears to be intermediate between simian and human foamy viruses. transient expression assays demonstrate that sfv-6 encodes a transactivator of v ...19947998839
characterization of the internal promoter of simian foamy viruses.simian and human foamy viruses (hfv and sfv), genetically related members of the spumavirus genus of retroviruses, have complex genome structures which encode the gag, pol, and env genes for virion proteins as well as additional open reading frames. one of these open reading frames is a viral transactivator, encoded by genes designated taf for sfv and bel-1 for hfv, which augments transcription directed by the long terminal repeat (ltr) through cis-acting targets in the u3 domain of the ltr. rec ...19948035481
identification and characterization of the bel 3 protein of human foamy virus.the human foamy virus (hfv) is a complex retrovirus that contains several regulatory and auxiliary bel genes besides the gag, pol, and env genes. in contrast to the gene products of bel 1 and bel 2/bet that were identified previously, the bel 3 protein has not been described to date. here we report the identification of bel 3 in hfv-infected cells by immunoprecipitation, indirect immunofluorescence, and expression cloning under the control of a strong heterologous promoter. bel 3 was immunopreci ...19947917520
absence of foamy virus dna in graves' disease.a report on the high prevalence of foamy virus dna in lymphocytes from french patients with graves' disease prompted us to investigate a similar cohort of 41 german patients. using pcr amplification and southern blot hybridization, we detected foamy virus dna only in lymphocytes of two accidentally infected humans and five naturally infected monkeys, as well as in dna samples from four graves' disease patients investigated in the french study. however, we failed to detect foamy virus dna in peri ...19947917521
absence of evidence for human spumaretrovirus sequences in patients with graves' disease. 19957712242
markers of foamy virus infections in monkeys, apes, and accidentally infected humans: appropriate testing fails to confirm suspected foamy virus prevalence in humans.foamy viruses (fvs) persist in healthy individuals of various mammalian species, including nonhuman primates. laboratory markers of fv infection are (1) virus in throat epithelium or peripheral blood lymphocytes (pbls), (2) proviral dna sequences in pbls and various solid organs, and (3) antibodies reactive to viral antigens on western blots, in radioimmunoprecipitation tests, and in immunofluorescence assays. using pcr and serological tests, we readily detected fv markers in naturally infected ...19957734189
establishment of carrier-state infection of a feline renal cell line with feline syncytial virus.although feline syncytial virus (fsv) is normally highly cytopathogenic in crandell feline kidney cells, a non-cytopathic persistent infection was established in the cells after cocultivation of the initially infected cells with uninfected cells 4 times. more than 90% of the persistently infected cells were positive for fsv antigen, and electron microscopy showed that the culture produced morphologically normal fsv. virus from the carrier culture was infectious, however, the titer of the virus f ...19957756428
replicating foamy virus-based vectors directing high level expression of foreign genes.replication-competent retroviral vectors (pfov-1 to -3 and -7) were constructed on the basis of an infectious human foamy virus molecular clone which has deletions in the u3 region of the long terminal repeat and in the 3' region of the genome, previously identified to be nonessential for virus replication in vitro. the cat and luciferase indicator genes were expressed as c-terminal fusion proteins to 215 amino acids of the viral bet protein in the pfov-1 vector. introduction of the foot-and-mou ...19957793069
a comparative study of higher primate foamy viruses, including a new virus from a gorilla.few foamy (spuma) retroviruses have been investigated in molecular detail, despite their previous isolation from several mamalian species, including ten neutralization serotypes from various primates. here, we have studied a new gorilla foamy virus (sfv-gg) and investigated its functional and phylogenetic relationship to the human (hfv) and other primate foamy viruses, including that recently described in orangutans (sfv-11). nucleotide sequencing of pcr products obtained from the r/u5 region of ...19957871729
phylogenetic analysis of primate foamy viruses by comparison of pol sequences.the relationship between primate foamy viruses was determined by comparing a 425-bp dna segment obtained by pcr using primers homologous to highly conserved portions of the pol gene. the phylogenetic tree of 14 foamy viruses investigated reflects the relationship between their host species: a cluster of asian old world monkey foamy viruses including simian foamy virus (sfv) prototypes 1 and 2 (isolated from macaca cyclopsis) is separated from african old world foamy viruses including prototype s ...19957886963
active foamy virus proteinase is essential for virus infectivity but not for formation of a pol polyprotein.to analyze proteolytic processing of foamy (spuma) retroviruses, two mutations were generated in the presumed active-site triplet asp-ser-gly in the predicted proteinase (pr) region of the human foamy virus (hsrv). the mutations changed either the presumed catalytic aspartic acid residue to a catalytically incompetent alanine or the adjacent serine to a threonine found in most cellular and retroviral proteases at this position. both mutations were cloned into the full-length infectious hsrv dna ...19957474150
cell cycle dependence of foamy retrovirus infection.in common with oncoviruses but unlike the lentivirus human immunodeficiency virus type 1, foamy (spuma) viruses require host cell proliferation for productive infection. we show that human immunodeficiency virus type 1 replicates in rd-cd4 cells regardless of the growth arrest condition of the cells, while murine leukemia virus is unable to infect growth-arrested rd-cd4 cells or cells progressing through a partial cell cycle that includes s phase but not mitosis. human foamy virus, like murine l ...19957474157
molecular biological characterization of the human foamy virus reverse transcriptase and ribonuclease h domains.foamy viruses form a separate group of retroviruses encoding a pol protein with at least four domains based on comparative sequence alignments. the polymerase and ribonuclease h domains of the human foamy virus (hfv) pol gene were expressed in escherichia coli either individually or in combination. the histidine-tagged hfv fusion proteins were subsequently purified to near homogeneity by affinity ni2+ chelate column chromatography. the polymerase and rnase h activities were characterized by perf ...19957483284
stem cell factor binding to retrovirus primer binding site silencers.using modified nuclear lysis and binding conditions, we have examined the binding of an embryonal carcinoma (ec) cell factor, binding factor a, to a stem cell-specific silencer which acts at the dna level and overlaps the moloney murine leukemia virus (m-mulv) proline primer binding site (pbs). following our protocol, we found that in vitro binding of factor a correlated with the in vivo activity of the m-mulv silencer. factor a bound specifically to the wild-type silencer element at room temper ...19957529329
human foamy virus and familial mediterranean fever in japan. 19957474216
haematological disorders associated with feline retrovirus infections.feline oncornavirus and lentivirus infections have provided useful models to characterize the virus and host cell factors involved in a variety of marrow suppressive disorders and haematological malignancies. exciting recent progress has been made in the characterization of the viral genotypic features involved in felv-associated diseases. molecular studies have clearly defined the causal role of variant felv env gene determinants in two disorders: the t-lymphocyte cytopathicity and the clinical ...19957663052
involvement of a spliced and defective human foamy virus in the establishment of chronic infection.human foamy retrovirus (hfv) is found as two proviruses (hfv and delta hfv) which differ by a splice-induced deletion within the bel1 transactivator gene. the defective delta hfv (which lacks a functional bel1 but harbors an intronless bet gene) is predominantly found in nonlytic infections in vitro as well as in vivo. here, we show that infection of cell lines stably transduced by delta hfv dna with the highly lytic hfv leads to chronic infections characterized by an absence of lysis, a balance ...19957636968
analysis of cross reactivity of retrovirus proteases using a vaccinia virus-t7 rna polymerase-based expression system.we have used the vaccinia virus-t7 rna polymerase-based expression system for studies on the activity of proteases from various retroviruses on homologous and heterologous gag polyproteins in eukaryotic cells. proteases from human immunodeficiency virus (hiv) types 1 and 2, equine infectious anaemia virus, human t cell leukaemia virus type 1 and human spumavirus were produced and were shown to cleave their cognate gag substrates produced in trans. analysis of cross reactivity revealed that lenti ...19957561754
internal transcriptional regulatory elements in hiv-1 and other retroviruses.the transcriptional regulation of retroviruses plays an important role in their pathogenesis. cis-acting elements have been identified in the long terminal repeat (ltr) at the 5' extremity of the integrated provirus. these elements determine the rate and the site of transcription initiation and consist of arrays of binding sites for transcription factors. recent studies have demonstrated the presence of additional regulatory elements, located outside of the ltr, within the transcribed region of ...19957580829
activation of hiv transcription by human foamy virus in transgenic mice.although infection by hiv-1 is the primary cause of aids, cofactorial agents of an infectious nature may be involved in the pathogenesis of the disease. the present work addresses the cofactorial potential of human foamy virus (hfv) in aids. it has been suggested that hfv seroprevalence reaches 5% in east africa, and hfv seroprevalence in east african patients suffering from aids and aids-related complex may be as high as 20%. although the pathogenic potential of hfv in humans has not yet been i ...19957603032
the human foamy virus internal promoter is required for efficient gene expression and infectivity.the human foamy or spumaretrovirus (hfv) is a complex retrovirus that codes for the three retroviral genes gag, pol, and env and the regulatory and accessory bel genes. a particular feature of hfv gene expression was recently described: not only does the hfv provirus contain the classical retroviral long terminal repeat promoter, a second functionally active promoter is present in the env gene upstream of the bel genes (m. löchelt, w. muranyi, and r. m. flügel, 1993, proc. natl. acad. sci. usa 9 ...19957831816
characterization of the human spuma retrovirus integrase by site-directed mutagenesis, by complementation analysis, and by swapping the zinc finger domain of hiv-1.the human spuma retrovirus or foamy virus integrase (hfv in) is an enzymatically active protein consisting of domains similar to other retroviral integrases: an amino-terminal hh-cc finger, a centrally located region with the conserved d, d-35-e protein motif required for catalytic activity and oligomerization, and at least one dna binding domain implicated in the 3' dna processing activity and integrase. recombinant, purified hfv in protein carrying 10 histidine residues displays a site-specifi ...19957852375
human foamy virus infection activates class i major histocompatibility complex antigen expression.we examined the effect of human foamy virus (hfv) infection on the expression of human major histocompatibility complex molecules. our data show that in vitro hfv infection of u373-mg glioblastoma cells results in increased expression of class i human leukocyte antigen (hla) and transcripts. transient transfection assays of plasmids containing the reporter gene chloramphenicol acetyl transferase driven by different 5' deletions of the hla-a11 class i promoter allowed identification of cis-acting ...19957534815
isolation of novel human endogenous retrovirus-like elements with foamy virus-related pol sequence.a new class of reverse transcriptase coding sequences was detected in reverse-transcribed rnas from human placenta by polymerase chain amplification with primers in highly conserved regions of the pol gene of mammalian retroviruses and retrotransposons. using one of these novel sequences as a probe to screen a human genomic library, we isolated retrovirus-like elements bordered by long terminal repeats and having a potential leucine trna primer-binding site. determination of the complete nucleot ...19957543594
mutational analysis of the reverse transcriptase and ribonuclease h domains of the human foamy virus.human foamy or spuma virus (hfv) codes for a distinct set of pol gen products. to determine the minimal requirements for the hfv enzymatic activities, defined residues of the reverse transcriptase (rt) and ribo-nuclease h (rnase h) domain of the hfv pol gene were mutated by site-specific pcr mutagenesis. the mutant gene products were bacterially expressed, purified by ni2+ chelate affinity chromatography and characterised by western blotting. the enzymatic activities of the individual recombinan ...19957544460
human foamy virus dna forms and expression in persistently infected dami megakaryocytic cells.we have characterized human foamy virus (hfv) proviral dna and determined hfv expression in a persistent infection model, the dami megakaryocytic cell line. molecular studies were performed on parental persistently infected cells (dami-p), as well as on derived clones (dami-cl). we report that in these nonlytic and non-hfv producer cells, viral dna was found to be integrated into the cellular genome and that the few free proviral forms detected in dami-p cells were deleted in their 5' ltr. our m ...19957546910
recent insights into the biology of the human foamy virus.human foamy virus (hfv) is a complex retrovirus with structural similarities to hiv and human t cell leukemia virus. there have been considerable advances in understanding the biology of hfv in cell cultures. however, viral behavior in vivo, and even viral detection, are still poorly understood. while hfv-transgenic mice develop neuromuscular disorders, attempts to associate hfv with a specific human disease have given inconclusive results.19957627455
regulation of foamy virus gene expression. 19957648870
identification of an er retrieval signal in a retroviral glycoprotein. 19957664333
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