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antigenic relationship of human foamy virus to the simian foamy viruses.a foamy virus isolated by achong et al. from a human nasopharyngeal carcinoma was studied to determine its antigenic relationship to the eight known simiam foamy viruses (sfv). using reciprocal cross-immunofluorescent and cross-neutralization techniques, we found the human isolate to be closely related to sfv type 6. in a seroepidemiological survey, neutralizing antibody to the human foamy virus was not detected in the sera of animal caretakers or laboratory personnel who routinely handled a wid ...197878897
human foamy virus: further characterization, seroepidemiology, and relationship to chimpanzee foamy viruses.a foamy virus present in human nasopharyngeal carcinoma tissue was studied for a number of biological properties, including range of cellular susceptibility, growth curve, evolution of cytopathic effect in relation to cellular fusion and intracellular viral distribution, reverse transcriptase activity, and buoyant density. the virus was also studied immunologically and found to be closely related to the chimpanzee foamy viruses, particularly simian foamy virus type 6, with which it shares common ...1978206631
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
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
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
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
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
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
search for retrovirus in the chronic fatigue syndrome.to examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus.19921479030
sequence analysis of the simian foamy virus type 1 genome.we have cloned the simian foamy virus type 1 genome (sfv1) and determined its nucleotide sequence. analysis of this genome reveals, in addition to the usual genes encoding retroviral capsid, reverse transcriptase, and envelope protein (respectively, gag, pol, and env), two open reading frames (orfs) between env and the long terminal repeat with partial homology to the human foamy virus (hfv) bel1 and bel2 genes. the first orf could code for a polypeptide of 312 amino acids (aa) showing 40% homol ...19911647358
progressive encephalopathy and myopathy in transgenic mice expressing human foamy virus genes.transgenic mice carrying the bel region of human foamy retrovirus (hfv) under transcriptional control of its own long terminal repeat expressed the transgene in their central nervous systems and in smooth and striated muscle tissues. the animals developed a progressive degenerative disease of the central nervous system and of the striated muscle. because expression of the transgene was closely correlated with the appearance of structural damage and inflammatory reactions were scanty, the disease ...19911650034
transcription factor ap-1 modulates the activity of the human foamy virus long terminal repeat.the human foamy virus (hfv) contains within the u3 region of its long terminal repeat (ltr) three perfect consensus sequences for the binding of the inducible transcription factor ap-1. results of dnase i footprint protection and gel retardation assays demonstrated that proteins in extracts of hela and bhk-21 cells as well as bacterially expressed jun and fos proteins bind to these ap-1 sites. by conducting transient expression assays using chloramphenicol acetyltransferase plasmids carrying ltr ...19911656100
analysis of splicing patterns of human spumaretrovirus by polymerase chain reaction reveals complex rna structures.mapping of transcripts of the human foamy virus genome was carried out in permissive human embryonic fibroblast cells by northern blot hybridization and s1 nuclease analysis. since several splice sites that are localized within a relatively narrow genomic region were detected, the polymerase chain reaction (pcr) was employed, and cloning and sequencing of the splice site junctions of the corresponding viral cdnas were subsequently performed. all spumavirus transcripts have a common but relativel ...19911846194
the transcriptional transactivator of human foamy virus maps to the bel 1 genomic region.the human foamy virus (hfv) genome possesses three open reading frames (bel 1, 2, and 3) located between env and the 3' long terminal repeat. by analogy to other human retroviruses this region was selected as the most likely candidate to encode the viral transactivator. results presented here confirmed this and showed further that a deletion introduced only into the bel 1 open reading frame of a plasmid derived from an infectious molecular clone of hfv abolished transactivation. in contrast, del ...19911846970
characterization of the transcriptional trans activator of human foamy retrovirus.the human foamy viruses, or spumaviruses, a distinct subfamily of complex human retroviruses, remain poorly understood both in terms of their pathogenic potential and in terms of the regulatory mechanisms that govern their replication. here, we demonstrate that the human spumaretrovirus shares with other complex human retroviruses the property of encoding a transcriptional trans activator of the homologous viral long terminal repeat. this regulatory protein is encoded by the viral bel-1 open rea ...19911850032
identification of the simian foamy virus transcriptional transactivator gene (taf).simian foamy virus type 1 (sfv-1), a member of spumavirus subfamily of retroviruses, encodes a transcriptional transactivator that functions to strongly augment gene expression directed by the viral long terminal repeat (ltr). the objective of this study was to identify the viral gene responsible for transactivation. nucleotide sequences between the env gene and the ltr of sfv-1 were determined. the predicted amino acid sequence revealed two large open reading frames (orfs), designated orf-1 (31 ...19911851862
relationship of the env genes and the endonuclease domain of the pol genes of simian foamy virus type 1 and human foamy virus.we have molecularly cloned and sequenced a portion of the simian foamy virus type 1 (sfv-1); open reading frames representing the endonuclease domain of the polymerase (pol) and the envelope (env) genes were identified by comparison with the human foamy virus (hfv). unlike the hfv genomic organization, the sfv-1 pol gene overlaps the env gene; thus, the open reading frames reported for hfv between pol and env is not present in sfv-1. comparisons of predicted amino acid sequences of hfv and sfv-1 ...19902152825
identification of the major immunogenic structural proteins of human foamy virus.we have identified the major immunogenic structural proteins of the human foamy virus (hfv), a distinct member of the foamy virus subfamily of retroviridae. radiolabelled viral proteins were immunoprecipitated from hfv-infected cells by foamy virus antisera of human and non-human primate origin. precipitated viral proteins were in the range of 31k to 170k. labelling of proteins with [14c]glucosamine or with [35s]methionine in the presence of tunicamycin, as well as endo-beta-n-acetylglycosaminid ...19902161055
simian foamy virus type 1 is a retrovirus which encodes a transcriptional transactivator.simian foamy viruses, members of the spumavirus subfamily of retroviruses, are found in a variety of nonhuman primates and, as yet, remain to be characterized with respect to genetic structure and regulation of viral gene expression. the genome of simian foamy virus type 1 (sfv-1), an isolate from rhesus macaques, has been molecularly cloned, and the role of the viral long terminal repeat (ltr) in transcriptional control has been investigated. the sfv-1 ltr is 1,621 base pairs long, and sequence ...19902370676
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
human foamy virus and familial mediterranean fever in japan. 19957474216
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
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
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
[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
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
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
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
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
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
regulation of foamy virus gene expression. 19957648870
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
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
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
human foamy virus bel1 transactivator contains a bipartite nuclear localization determinant which is sensitive to protein context and triple multimerization domains.the bel1 protein of human foamy virus is a 300-amino-acid nuclear regulatory protein which transactivates the gene expression directed by the homologous long terminal repeat and the human immunodeficiency virus type 1 long terminal repeat. while previous reports suggested that the single basic domain of bel1 from residues 211 to 222 and/or 209 to 226 is necessary and sufficient for efficient nuclear localization (l. k. venkatesh, c. yang, p. a. theodorakis, and g. chinnandurai, j. virol. 67:161- ...19957815546
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
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
human foamy virus infection in myasthenia gravis. 19947906819
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
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
[present status of retroviruses in human infectious disease].retroviruses have been shown to be oncogenic in many animals for decades. in humans, retroviruses became worth of interest no sooner than in the early eighties. hiv is at the moment the last one of the well studied human retroviruses. besides, htlv-1, the prevalence of which is geographically restricted, is associated with adult t-cell leukemia/lymphoma, and with chronic myelopathies. this virus, as well as the closely related and rarer htlv-2, is transmitted sexually, probably perinatally, and ...19947939298
retroviral synthetic peptide serum antibodies in human sporadic amyotrophic lateral sclerosis.we examined 101 sera from 32 adult sporadic amyotrophic lateral sclerosis (als) patients, including nine with positive enzyme-linked immunosorbent assay (elisa) serum antibodies against human spuma retrovirus (hsrv) [human foamy virus (hfv)] envelope (env) and/or capsid (gag) proteins, for peptide seroreactivity. synthetic peptides 10 to 14 amino acids in length were selected from hsrv (3), maedi-visna virus (1), human nerve growth factor-beta (1), and human amyloid-beta sequences (1). eighteen ...19948008625
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
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
retroviruses and inflammatory myopathies in humans and primates.the human immunodeficiency virus (hiv), the human t cell lymphotropic virus (htlv-1), the human foamy retrovirus and the simian immunodeficiency viruses have been associated with the development of an inflammatory myopathy in humans and primates. the myopathy caused by hiv and htlv-1 is not due to direct infection of the muscle by these viruses, but rather due to an immunopathologic process triggered by the viruses, mediated by autoaggressive cd8+ cells in the context of mhc-class i antigen expr ...19938156147
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
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
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
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
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
bel-1 transactivator responsive sequences in the long terminal repeat of human foamy virus.cis-regulatory elements in the long terminal repeat (ltr) of human foamy virus (hfv) were identified by using ltr mutants to transiently express the chloramphenicol acetyl-transferase gene after co-transfection with an expression plasmid for the virus bel-1 (transactivator) gene. the r-u5 region and an element in the 5' u3 region were found to negatively influence hfv gene expression. the complete bel-1 responsive region was mapped to extend from nucleotide position -471 to position -93 relative ...19938356798
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
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
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
[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
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
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
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
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
foamy virus vectors.human foamy virus (hfv) is a retrovirus of the spumavirus family. we have constructed vectors based on hfv that encode neomycin phosphotransferase and alkaline phosphatase. these vectors are able to transduce a wide variety of vertebrate cells by integration of the vector genome. unlike vectors based on murine leukemia virus, hfv vectors are not inactivated by human serum, and they transduce stationary-phase cultures more efficiently than murine leukemia virus vectors. these properties, as well ...19968523528
the human foamy virus pol gene is expressed as a pro-pol polyprotein and not as a gag-pol fusion protein.it has been reported recently that the human foamy virus (hfv) pol polyprotein of 120 kda is synthesized in the absence of the active hfv aspartic protease. to gain more information on how the 120-kda pro-pol protein is synthesized, mutant hfv genomes were constructed and the resulting proviruses were analyzed with respect to hfv pol expression and infectivity. hfv proviruses that contain termination codons in the nucleocapsid domain of gag and thus lack a gag-pol overlap region assumed to be re ...19968551561
productive persistent infection of hematopoietic cells by human foamy virus.human foamy virus can establish persistent infections in human hematopoietic cell lines, such as h92.1.7 (erythroblastoid cells), jurkat (cd4+ t cells), and u937 (myeloid-monocytic cells). the infection is characterized by constant production of infectious viruses (for > 2 1/2 years) with no cytopathic effects on the host cells. electron microscopy of the infected cells showed a viral morphology similar to that observed for particles produced after acute infection. we have detected, in addition ...19968551590
the transcriptional transactivator of simian foamy virus 1 binds to a dna target element in the viral internal promoter.the transcriptional transactivator (tas) of simian foamy virus type 1 strongly augments gene expression directed by both the promoter in the viral long terminal repeat and the newly discovered internal promoter located within the env gene. a region of 121 bp, located immediately 5' to the tata box in the internal promoter, is required for transactivation by tas. the present study aimed to identify the precise tas-responsive target(s) in this region and to determine the role of tas in transcripti ...19968552631
infectious proviral clones of chimpanzee foamy virus (sfvcpz) generated by long pcr reveal close functional relatedness to human foamy virus.infectious proviral clones of simian foamy virus isolated from chimpanzee (sfvcpz) were generated by long pcr. two overlapping fragments representing the complete provirus were amplified from genomic dna of infected cells. four 8.8-kbp amplimers extending from base 1 of the provirus into the env gene and five 4.45-kbp amplimers reaching from env to the end of the 3'-ltr were cloned into pcr ii. subsequently, the proviral fragments were combined in a chessboard manner to generate 20 plasmids cont ...19958553577
human foamy virus replication: a pathway distinct from that of retroviruses and hepadnaviruses.human foamy virus (hfv) is the prototype of the spumavirus genus of retroviridae. in all other retroviruses, the pol gene products, including reverse transcriptase, are synthesized as gag-pol fusion proteins and are cleaved to functional enzymes during viral budding or release. in contrast, the pol protein of hfv is translated from a spliced messenger rna and lacks gag domains. infectious hfv particles contain double-stranded dna similar in size to full-length provirus, suggesting that reverse t ...19968599113
analysis of the determinants of neurotropism and neurotoxicity of hfv in transgenic mice.the bel-1 protein of human foamy virus (hfv) is a transactivator acting on the u3 region of the long terminal repeat and on an internal promoter (ip) immediately upstream of the bel genes. an hfv transgene called delta gpe, containing both promoters and all bel genes, is expressed in the central nervous system and induces neurodegeneration in mice. to dissect the role of individual promoters and bel genes on transgene expression and neurotoxicity we generated transgenic mice with a construct ter ...19968607263
regulation of expression and pathogenic potential of human foamy virus in vitro and in transgenic mice. 19968608720
in vitro infection of primary and retrovirus-infected human leukocytes by human foamy virus.the infectivity of human foamy virus (hfv) was examined in primary and cultured human leukocytes. cell-free infectious viral stocks of hfv were prepared from the human kidney cell line 293 transfected with an infectious molecular clone of hfv. hfv productively infects a variety of human myeloid and lymphoid cell lines. in addition, primary cell cultures enriched for human cd4+, monocytes and brain-derived microglial cells, were readily infected by hfv. interestingly, while infected primary cd4+ ...19968627751
the human foamy virus bel-1 transcription factor is a sequence-specific dna binding protein.the bel-1 transcriptional transactivator encoded by human foamy virus (hfv) can efficiently activate gene expression directed by both the hfv long terminal repeat (ltr) and internal (int) promoter elements. by dna footprinting and gel retardation analysis, we demonstrate that bel-1 can specifically bind to discrete sites in both the ltr and int promoter elements in vitro. however, transactivation of the hfv ltr by bel-1 was observed to require not only the promoter-proximal bel-1 binding site id ...19968648727
lymphocytes are the major reservoir for foamy viruses in peripheral blood.simian and human foamy virus (fv) dna can be readily detected in peripheral blood leukocytes. however, it is unknown which leukocyte populations harbor the virus in vivo. we, therefore, analyzed blood samples from nine african green monkeys, four chimpanzees, and two humans for the presence of foamy virus proviral dna in different facs-purified leukocyte populations, using a highly sensitive nested polymerase chain reaction (pcr). the cd8+ lymphocytes were pcr positive in all 15 samples and the ...19968661433
transactivation of the two promoters of sfv-3 by different mechanisms.simian foamy virus type 3 (sfv-3), a member of the spumavirus genus of retroviruses, has a complex genome organization and encodes two open reading frames (orfs), in addition to the structural genes gag, pol, and env. orf-1 encodes a viral transcriptional transactivator designated taf (transactivator of foamy viruses) which augments transcription from the viral long terminal repeat (ltr). it was recently shown that human foamy virus, as well as the simian viruses sfv-1 and sfv-3, contains a seco ...19968661448
inactivation of murine leukemia virus by compounds that react with the zinc finger in the viral nucleocapsid protein.all retroviral nucleocapsid (nc) proteins, except those of spumaretroviruses, contain one or two copies of the conserved sequence motif c-x2-c-x4-h-x4-c. the conserved cysteine and histidine residues coordinate a zinc ion in each such motif. rice et al. (w. g. rice, j. g. supko, l. malspeis, r. w. buckheit, jr., d. clanton, m. bu, l. graham, c. a. schaeffer, j. a. turpin, j. domagala, r. gogliotti, j. p. bader, s. m. halliday, l. coren, r. c. sowder ii, l. 0. arthur, and l. e. henderson, science ...19968764002
the simian foamy virus type 1 transcriptional transactivator (tas) binds and activates an enhancer element in the gag gene.simian and human foamy viruses (sfv and hfv) encode a transcriptional transactivator, tas, which governs the levels of viral transcripts initiated by both the promoter in the long terminal repeat (ltr) and the internal promoter (ip) located within the env gene of these viruses. tas-responsive target elements,(tre) ltr in the ltr and (tre) ip in the env gene, are located 5' of the tata box in both viral promoters and function as orientation- and position-independent enhancers. we have identified ...19968794326
molecular biology of the human foamy virus.foamy viruses also known as spumaretroviruses are complex retroviruses infecting cell lines with no apparent specific cellular tropism and induce the formation of multinucleated cells with numerous vacuoles. far less well characterized than oncoviruses and lentiviruses, this class of viruses is thought to be innocuous in vivo. however, several important discoveries on foamy viruses brought new insights in the field of retrovirology.19968797732
expression of human foamy virus reverse transcriptase involves a spliced pol mrna.in human foamy virus (hfv) the reverse transcriptase is expressed independently of the gag protein as a 127-kda pol precursor molecule. evaluating the mechanism of pol expression we identified a spliced mrna which uses the main 5' splice donor and a splice acceptor site located in the gag gene. the significance of this spliced transcript for hfv pol expression was studied by constructing a virus with a mutated splice acceptor site. this virus was unable to express detectable pol proteins after t ...19968862427
isolation and characterization of infectious full-length dna clones of chimpanzee foamy viruses sfv6 and sfv7: evidence for a taf-dependent internal promoter.we have cloned complete viral genomes directly from hirt supernatant dnas of simian foamy virus types 6 and 7 (sfv6 and sfv7) -infected cells. these clones were shown to be infectious by transfection into cells and subsequent infection of susceptible cells either by cocultivation or by passage of cell-free supernatants. the presence of virus particles, suggested by a typical cytopathic effect, was confirmed by electron microscopy. these viruses were characterized at different levels of the repli ...19968882337
in vitro studies on interferon-inducing capacity and sensitivity to ifn of human foamy virus.we demonstrate in this article that human foamy virus (hfv) fails to induce interferon (ifn) production in two different human tissue culture cell lines: u373-mg and av3. we also show the effect of human alpha-, beta- and gamma ifn on the multiplication cycle of hfv. treatment of cells with 100 iu/ml of any ifn led to strong inhibition of an hfv-induced cytopathic effect. this effect was associated with a significant diminution of reverse transcriptase activity in supernatant fluids of ifn-treat ...19968882338
no evidence of antibody to human foamy virus in widespread human populations.the first human foamy virus (hfv) to be described was isolated from nasopharyngeal carcinoma tissue from a kenyan patient. early seroepidemiology concluded that there was a significant infection rate, particularly among africans. awareness of foamy viruses as potential vectors has stimulated interest in the natural seroprevalence of hfv infection. we, therefore, investigated the prevalence of hfv infection in more than 5000 human sera collected from diverse populations. to maximize the chances o ...19968893055
inhibition of the in vitro infectivity and cytopathic effect of human foamy virus by dideoxynucleosides.human foamy virus (hfv) is a human retrovirus that has not been clearly associated with human disease. in this study, we tested the capacity of nucleoside derivatives to inhibit the infectivity and cytopathic effect of hfv in t-lymphoblastoid cells in vitro. h9 cells showed a dramatic cytopathic effect 3 weeks after exposure to hfv. at this time, viral infection was demonstrated by detection of viral antigens by immunofluorescence staining, release of reverse transcriptase activity (rt) in the s ...19968893056
transduction of hematopoietic cells by foamy virus vectors.foamy viruses are retroviruses of the spumavirus family that are often isolated from primary cultures of primate cells. we previously constructed vectors based on human foamy virus (hfv) and found that they were able to transduce a wide variety of vertebrate cells by integration of the vector genome. here we show that several types of hematopoietic cells are efficiently transduced by an hfv vector that encodes alkaline phosphatase (ap). these cell types include transformed cell lines and primary ...19968896436
analysis of west african hunters for foamy virus infections.foamy viruses are a genus of complex retroviruses that infect a wide variety of mammals. however, a clear association with any disease process has yet to be proven for these viruses. a higher human seroprevalence was reported in african populations, perhaps due to exposure to simian foamy viruses (sfv) endemic in primates. however, the earlier serologic surveys were not confirmed by studies employing nucleic acid amplification. foamy virus infections of humans clearly do occur as rare zoonoses a ...19968959250
the carboxyl terminus of the human foamy virus gag protein contains separable nucleic acid binding and nuclear transport domains.the gag protein of human foamy virus (hfv) lacks cys-his boxes present in the nucleocapsid (nc) domains of other retroviruses; instead it contains three glycine-arginine-rich motifs (gr boxes). we have expressed the carboxyl end of hfv gag containing the gr boxes (the nc domain equivalent) and analyzed its nucleic acid binding properties. our results show that the nc domain of hfv gag binds with high affinity to both rna and dna, in a sequence-independent manner, as determined by filter binding ...19968970944
characterization of the spliced pol transcript of feline foamy virus: the splice acceptor site of the pol transcript is located in gag of foamy viruses.foamy viruses, or spumaviruses, are distinct members of the retroviridae. here we have characterized the long terminal repeat of the feline, or cat, foamy virus by determining the locations of the transcriptional start site and the poly(a) addition site. the splice donor and splice acceptor sites of the subgenomic mrna responsible for pro-pol protein expression were identified by nucleotide sequencing of the corresponding cdnas. the leader exon of the feline foamy virus is 57 nucleotides long. t ...19968971036
nuclear targeting of incoming human foamy virus gag proteins involves a centriolar step.the pathways used in the transport of retroviral genomes to the nucleus are poorly identified. analyzing the intracellular localization of incoming foamy viruses, we have found that the gag antigens and the viral genome accumulate in a distinct perinuclear domain identified as the centrosome. colchicine treatment completely abolished pericentriolar targeting of human foamy virus (hfv) proteins, suggesting a role for microtubules in the transport of the incoming viral proteins to the centrioles. ...19978995637
expression and maturation of human foamy virus gag precursor polypeptides.in this report, we address the processing of the gag polypeptides of human foamy virus previously reported to be atypical. in the cytoplasm or the nucleus of infected cells as well as in free virus particles, two gag precursor polypeptides were identified at approximately 72 and 68 kda, p72 giving rise to p68 by a maturation process. efficient maturation of gag precursors was observed only in two situations: (i) during the early steps of virus adsorption and (ii) under experimental conditions, i ...19978995691
characterization of human foamy virus proteins expressed by recombinant vaccinia viruses.we report the generation of recombinant vaccinia viruses (vvs) expressing the gag, pol, bel-1, and bet open reading frames of human foamy virus (hfv), and the establishment of a transient, vv-t7 rna polymerase-directed expression system for the hfv env gene. the correct expression of the hfv proteins was demonstrated by radioimmunoprecipitation using monospecific rabbit antisera, by analysis of the subcellular distribution (for vvgag, vvpol, vvbel-1, and vvbet), and by the ability to induce sync ...19979100994
long-term persistent infection of domestic rabbits by the human foamy virus.human foamy virus (hfv) belongs to the spumaretrovirus group of the retroviridae taxonomic family. attempts to associate hfv or other foamy viruses to a specific pathology still remain unsuccessful. however, viral gene expression as well as tissue-specific tropism in an in vivo context remain poorly analyzed. to address this issue, we have infected domestic rabbits with a single dose of hfv and followed them at the biological and molecular levels for 5 years. no apparent pathology was detectable ...19979123833
protein composition and morphology of human foamy virus intracellular cores and extracellular particles.characterization of human foamy virus (hfv) gag-encoded precursors and the search for a gag-pol polyprotein and mature proteins derived from proteolytic processing were carried out in hfv-infected cells and with purified preassembled cores and extracellular virus by western blotting and radioimmunoprecipitation using antisera against synthetic peptides corresponding to putative gag and protease proteins. precursor proteins, pr78gag/74gag and pr135pol, were found in the nucleus of epithelial and ...19979123838
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