Publications

structural and evolutionary analysis of an orangutan foamy virus.	the full-length proviral genome of a foamy virus infecting a bornean orangutan was amplified, and its sequence was analyzed. although the genome showed a clear resemblance to other published foamy virus genomes from apes and monkeys, phylogenetic analysis revealed that simian foamy virus sfvora was evolutionarily equidistant from foamy viruses from other hominoids and from those from old world monkeys. this finding suggests an independent evolution within its host over a long period of time.	2003	12857929
the replication strategy of foamy viruses.	the replication strategy of foamy viruses diverges in many aspects from what is commonly accepted as the rules of retroviral replication. although many questions on the details of the replication pathway are still unanswered, it appears that foamy viruses have adopted a strategy which functionally bridges the retroviral and the hepadnaviral replication pathways. a number of experimental findings in favour of the view that foamy viruses are reverse transcribing dna viruses which integrate into th ...	2003	12908766
foamy virus transactivation and gene expression.	an overview of the pattern and mechanisms of spuma or foamy virus (fv) gene expression is presented. fvs are complex retroviruses with respect to their genetic outfit and the elements used to control and regulate expression of the viral genome. the increased insight into transcriptional and posttranscriptional mechanisms has revealed that the fvs are distinct, unconventional retroviruses clearly apart from the orthoretroviruses. although less characterized than the orthoretroviruses, fvs have se ...	2003	12908767
proteolytic processing of foamy virus gag and pol proteins.	the foamy viral proteases (fv prs) are set apart from other retroviral processing enzymes by unique features. the first remarkable property is that fv prs are enzymatically active as high-molecular-mass pro-pol proteins. hence there exist multiple forms of active fv prs that likely contribute to cleavage site specificity. a fv pr of low molecular size is not detectable in purified virions, in contrast to prs of other retroviruses that are found in virus particles. because the major part of pol r ...	2003	12908768
particle assembly and genome packaging.	foamy virus (fv) replication is distinct from that of all other retroviruses in many respects, including viral assembly. in fact, the viral assembly pathway is rather similar to that of hepadnaviruses such as hepatitis b virus. foamy virus gag does not contain landmark retroviral assembly domains such as the major homology region, cys-his boxes, or a defined m domain. like hepadnaviruses, the fv gag protein is not cleaved and contains arginine-rich regions at the carboxyl terminus. in addition, ...	2003	12908769
the foamy virus envelope glycoproteins.	the main functions of retroviral glycoproteins are recognition and binding to the cellular virus receptor as well as fusion of viral and cellular lipid membranes to release the viral particle into the cytoplasm of the host cell. foamy viruses (fvs) are a special group of retroviruses with a very broad host range that use a currently unknown cellular receptor for entry. nevertheless, many functions of the fv envelope glycoproteins in the viral replication cycle have been characterized in detail o ...	2003	12908770
foamy virus vectors.	gene therapy is a promising novel treatment for a variety of human diseases. successful application of gene therapy requires the availability of vehicles with the ability to efficiently deliver and express genes. viral vectors are efficient means of transferring a gene of interest into target cells. current available vehicles for gene transfer are either inefficient or potentially unsafe for human gene therapy applications. foamy viruses offer a fresh alternative vector system for gene transfer ...	2003	12908771
replication of primate foamy viruses in natural and experimental hosts.	foamy viruses (fvs) are common apathogenic retroviruses readily spread by horizontal transmission in nonhuman primate and some other mammalian host populations. primate fv infections have been known for half a century, i.e., 15 years before the definition of retroviruses and another 15 years before the detection of primate immune deficiency viruses. the emerging interest in human retroviruses included primate fv, and although the role of human hosts for fv was greatly overestimated temporarily, ...	2003	12908772
human infection with foamy viruses.	virtually all nonhuman primate species investigated thus far including prosimians, new world and old world monkeys and apes all harbor distinct and species-specific clades of simian foamy virus (sfv). however, evidence supporting the existence of a human-specific foamy virus (fv) is not yet available. early reports describing widespread infection of healthy and sick humans with fv could not be confirmed. in contrast, all fv infections documented in humans are of zoonotic origin and are identifie ...	2003	12908773
current developments in the design of onco-retrovirus and lentivirus vector systems for hematopoietic cell gene therapy.	over the past dozen years, the majority of clinical gene therapy trials for inherited genetic diseases and cancer therapy have been performed using murine onco-retrovirus as the gene delivery vector. the earliest systems used were relatively inefficient in both the rates of transduction and expression of the transgene. formidable obstacles inherent in the cell biology and/or the immunology of the target cell systems limited the efficacy of gene therapy for many target diseases. development of no ...	2003	12676350
foamy virus envelope glycoprotein is sufficient for particle budding and release.	foamy viruses (fvs) are classified in the family retroviridae, but recent data have shown that they are not conventional retroviruses. notably, several characteristics of their particle replication strategies are more similar to those of hepatitis b virus (hbv) than those of typical retroviruses. compared to conventional retroviruses, which require only gag proteins for budding and release of virus-like particles (vlps), both fv and hbv require env proteins. in the case of hbv, env (s protein) a ...	2003	12551971
isolation of cytomegalovirus and foamy virus from the drill monkey (mandrillus leucophaeus) and prevalence of antibodies to these viruses amongst wild-born and captive-bred individuals.	drill monkeys (mandrillus leucophaeus) are an endangered species whose indigenous viral flora is largely unknown. we report here the isolation and characterization of both a cytomegalovirus (drcmv) and a foamy virus (sfv-drl) from drill monkeys. phylogenetic analysis of dna sequence data placed the drcmv within a primate cmv clade, and showed that sfv-drl was closely related to baboon foamy viruses. elisa analysis demonstrated that drcmv shared common epitopes with other primate cmvs but was dis ...	2003	12607096
foamy virus envelope glycoprotein-mediated entry involves a ph-dependent fusion process.	in general, enveloped viruses use two different entry strategies and are classified accordingly into ph-dependent and ph-independent viruses. different members of the retrovirus family use one or the other strategy. little is known about the uptake of foamy viruses (fv), a special group of retroviruses, into the target cells. in this study, we examined the ph dependence of fv entry by analyzing fv envelope glycoprotein (env)-mediated infection of target cells with murine leukemia virus or fv vec ...	2003	12663779
scoliosis in an orangutan.	the first case of scoliosis in an orangutan spine is reported.	2003	12671370
the promyelocytic leukemia protein does not mediate foamy virus latency in vitro.	spumaviruses, commonly called foamy viruses, are complex retroviruses that establish life-long persistent infections in the absence of accompanying pathology. depending upon cell type, infection of cells in tissue culture cells can result in either lytic replication, persistence, or latency. the cellular factors that mediate foamy virus (fv) latency are poorly understood. in this study we show that the only known inhibitor of fv replication, the promyelocytic leukemia protein (pml), which binds ...	2003	12525655
establishment of a gfp-based indicator cell line to quantitate feline foamy virus.	to quantitate infectious feline foamy virus (fefv), crandell feline kidney (crfk) cells were transfected with the gfp gene under the control of the fefv long terminal repeat (ltr) for establishing an indicator cell line named ffg cells. the fefv activates promoter activity of the ltr to express green fluorescent protein (gfp) upon infection. the titers determined by gfp-positive ffg cells (gfp-based assay) were higher than those determined by the cytopathic effects-positive crfk cells (cpe-based ...	2003	12711054
comparison of three retroviral vector systems for transduction of nonobese diabetic/severe combined immunodeficiency mice repopulating human cd34+ cord blood cells.	the use of recombinant vectors based on wild-type viruses that are absent in humans and are not associated with any disease in their natural animal hosts or in accidentally infected humans would add an additional level of safety for human somatic gene therapy approaches. these criteria are fulfilled by foamy viruses (fvs), a family of complex retroviruses whose members are widely found among mammals and are apathogenic in all hosts. here, we show by comparison of identically designed vector cons ...	2003	12718762
screening for simian foamy virus infection by using a combined antigen western blot assay: evidence for a wide distribution among old world primates and identification of four new divergent viruses.	simian foamy viruses (sfvs) belong to a genetically and antigenically diverse class of retroviruses that naturally infect a wide range of nonhuman primates (nhps) and can also be transmitted to humans occupationally exposed to nhps. current serologic detection of sfv infection requires separate western blot (wb) testing by using two different sfv antigens [sfv(agm) (african green monkey) and sfv(cpz) (chimpanzee)]. however, this method is labor intensive and validation is limited to only small n ...	2003	12758172
features of the env leader protein and the n-terminal gag domain of feline foamy virus important for virus morphogenesis.	previous studies have shown that foamy virus (fv) particle budding, especially the involvement of the viral env glycoprotein is different from that of other (ortho) retroviruses: the n-terminal env leader protein elp is a constituent of released fv particles. a defined sequence in elp required for particle budding binds to the ma domain of gag. to extend these findings, we show that feline fv elp is a membrane-anchored protein with the n-terminus located inside the particle. thus, the internal/c ...	2003	12781711
application of chimeric feline foamy virus-based retroviral vectors for the induction of antiviral immunity in cats.	in order to define the potential and applicability of replication-competent foamy virus-based vaccine vectors, recombinant feline foamy virus (ffv) vectors encoding defined segments of the feline calicivirus (fcv) capsid protein e domain were constructed. in cell cultures, these ffv-fcv vectors efficiently transduced and expressed a hybrid fusion protein consisting of the essential ffv bet protein and the attached fcv e domains. the stability of the vectors in vitro was inversely correlated to t ...	2003	12829823
non-primate foamy viruses.	foamy viruses (pfvs), also called spumaviruses, are complex retroviruses inducing a characteristic cytopathic effect in cell culture, leading rapidly to cell lysis. these viruses have been isolated mostly in non-human primates, but three non primate pfvs were characterized, namely the bovine foamy virus, the feline foamy virus and more recently the equine foamy virus. in their hosts, pfvs seem to be apathogenic, mirroring an efficient control of virus replication in vivo. comparing the biology o ...	2003	12908774
understanding xenotransplantation risks from nonhuman primate retroviruses.	significant progress in making animal-to-human transplantation a viable adjunct to human organ donation will require a greater understanding of the intricacies of immunologic rejection. recent success in generating cloned knockout piglets increases the possibility that xenotransplantation may find its way into the clinics. nonhuman primates' organs have been used for human transplants in the past and there is reason to believe that if ethical considerations and inherent problems with supply were ...	2003	12934943
feline foamy virus genome and replication strategy.	crucial aspects of the foamy virus (fv) replication strategy have so far only been investigated for the prototypic fv (pfv) isolate, which is supposed to be derived from nonhuman primates. to study whether the unusual features of this replication pathway also apply to more-distantly related fvs, we constructed feline fv (ffv) infectious molecular clones and vectors. it is shown by quantitative rna and dna pcr analysis that ffv virions contain more rna than dna. full-length linear dna was found i ...	2003	14557618
retrotransposition and cell-to-cell transfer of foamy viruses.	a remarkable feature of the prototype foamy virus (pfv) replication pathway has been reported to consist of the ability to retrotranspose intracellularly with high efficiency (m. heinkelein, t. pietschmann, g. jármy, m. dressler, h. imrich, j. thurow, d. lindemann, m. bock, a. moebes, j. roy, o. herchenröder, and a. rethwilm, embo j. 19:3436-3345, 2000). pfv intracellular retrotransposition (irt) was reported to be enhanced by coexpression of fusion-defective envelope protein. to investigate the ...	2003	14557671
demonstration of feline foamy virus in experimentally infected cats by immunohistochemistry.	foamy viruses (fv) are complex retroviruses which are commonly isolated from cats, cattle and non-human primates. the infection is persistent and infected animals have a sustained antibody response. the role of fv in diseases remains unclear, in cats, a possible association with uncharacterized renal symptoms remains to be confirmed. to demonstrate feline fv (ffv) in tissues of experimentally infected cats three polyclonal monospecific antisera from rabbits against three different viral proteins ...	2003	14633220
potential of zoonotic transmission of non-primate foamy viruses to humans.	the zoonotic introduction of an animal pathogen into the human population and the subsequent extension or alteration of its host range leading to the successful maintenance of the corresponding pathogen by human-to-human transmission pose a serious risk for world-wide health care. such a scenario occurred for instance by the introduction of simian immunodeficiency viruses into the human population resulting in the human immunodeficiency viruses (hiv) and the subsequent aids pandemic or the propo ...	2003	14633194
determinants of foamy virus envelope glycoprotein mediated resistance to superinfection.	little is known about the nature of foamy virus (fv) receptor molecules on target cells and their interaction with the viral glycoproteins. similar to other viruses, cellular expression of the fv env protein is sufficient to induce resistance to exogenous fv, a phenomenon called superinfection resistance (sir). in this study we define determinants of the fv env protein essential for mediating sir. fv env requires the extracellular domains of the su and the tm subunits as well as membrane anchora ...	2003	14517077
a cophylogenetic perspective of rna-virus evolution.	the extent to which viruses and their hosts codiverge remains an open question, given that numerous cases of both "cospeciation" and horizontal switching have recently been documented. dna viruses that form persistent infections are thought to be the most likely candidates for phylogenetic congruence. phylogenetic reconciliation analysis was used to compare established phylogenies for four rna viruses and their hosts. the analysis employs a cophylogeny mapping technique, implemented in treemap v ...	2004	12949128
kinetics and characteristics of replication-competent revertants derived from self-inactivating foamy virus vectors.	in this study, self-inactivating (sin) retroviral vectors based on feline foamy virus (ffv) were constructed and analysed. the ffv sin vectors were devoid of the core ffv long terminal repeat promoter plus upstream sequences but contained all structural and regulatory genes. this design allowed sensitive detection of replication-competent revertants (rcrs). the ffv sin vectors efficiently transduced the green fluorescence protein into recipient cells. however, rcrs appeared after serial passages ...	2004	14973540
frequent simian foamy virus infection in persons occupationally exposed to nonhuman primates.	the recognition that aids originated as a zoonosis heightens public health concerns associated with human infection by simian retroviruses endemic in nonhuman primates (nhps). these retroviruses include simian immunodeficiency virus (siv), simian t-cell lymphotropic virus (stlv), simian type d retrovirus (srv), and simian foamy virus (sfv). although occasional infection with siv, srv, or sfv in persons occupationally exposed to nhps has been reported, the characteristics and significance of thes ...	2004	14990698
a potential live vector, foamy virus, directed intra-cellular expression of ovine interferon-tau exhibited the resistance to hiv infection.	interferon-tau (ifn-tau), produced by the embryonic trophectoderm, is a member of type i ifns required for the establishment of pregnancy in the ruminant ungulates. although this ifn possesses antiviral activity similar to other type i ifns, the effectiveness of ifn-tau as an antiviral agent has not been well characterized. to investigate possible antiviral effects of ovine ifn-tau (oifn-tau), oifn-tau-gst fusion protein was expressed in e. coli bl21, from which the purified protein isolated pos ...	2004	15031537
naturally acquired simian retrovirus infections in central african hunters.	hunting and butchering of wild non-human primates infected with simian immunodeficiency virus (siv) is thought to have sparked the hiv pandemic. although siv and other primate retroviruses infect laboratory workers and zoo workers, zoonotic retrovirus transmission has not been documented in natural settings. we investigated zoonotic infection in individuals living in central africa.	2004	15043960
formalin-inactivated bovine rsv vaccine enhances a th2 mediated immune response in infected cattle.	safe rsv vaccine development has challenged the medical community since a formalin-killed rsv vaccine caused disease exacerbation in the 1960s. disease was replicated using the bovine rsv system in one of two studies. the studies differed in viral protein dose and length of time between vaccination and infection. disease exacerbation occurred in study 2 (previously reported). we hypothesized that low protein concentration in study 2's vaccine stimulated a th2/ige response that enhanced disease. ...	2004	15063570
foamy virus--adenovirus hybrid vectors.	to confer adenovirus vectors (adv), the feature of integration into the host cell genome hybrid vectors were characterized in vitro, which express vectors derived from the prototypic foamy virus (fv) in the backbone of a high-capacity adv. fvs constitute a subfamily of retroviruses with a distinct replication pathway and no known pathogenicity. in the absence of envelope glycoprotein, the prototypic fv behaves like a retrotransposon, while it behaves like an exogenous retrovirus in its presence. ...	2004	14724670
transient foamy virus vector production by adenovirus vectors.	the genome of the prototype foamy virus (pfv) has been introduced into an adenoviral/pfv hybrid vector and tested for stable in vitro gene transfer. three different adenoviruses are used to encode: (i) the pfv structural genes gag and pol (ad-gagpoldeltapaci); (ii) the pfv structural gene env (ad-env); and (iii) the pfv vector genome (ad-md9) encoding the transgene (the enhanced green fluorescent protein (egfp) gene). following cotransduction by the three adenoviruses, the target cells become tr ...	2004	14737091
maternally derived humoral immunity to bovine viral diarrhea virus (bvdv) 1a, bvdv1b, bvdv2, bovine herpesvirus-1, parainfluenza-3 virus bovine respiratory syncytial virus, mannheimia haemolytica and pasteurella multocida in beef calves, antibody decline by half-life studies and effect on response to vaccination.	the passive immunity transferred to calves from their dams was investigated in a beef herd to determine half-life of antibody, estimated time to seronegative status and effect on immunization. one hundred two beef calves in a commercial ranch under standard management conditions were utilized. samples were collected at branding (day 0). this was the first possible date to collect samples postcalving. this was approximately 2 months postcalving, and days 95 and 116. the calves were divided into t ...	2004	14741155
cell cycle requirements for transduction by foamy virus vectors compared to those of oncovirus and lentivirus vectors.	retroviral vectors based on foamy viruses (fv) are efficient gene delivery vehicles for therapeutic and research applications. while previous studies have shown that fv vectors transduce quiescent cell cultures more efficiently than oncoviral vectors, their specific cell cycle requirements have not been determined. here we compare the transduction frequencies of fv vectors with those of onco- and lentiviral vectors in nondividing and dividing normal human fibroblasts by several methods. fv vecto ...	2004	14963129
absence of human t-cell lymphotropic virus type i and human foamy virus in thymoma.	the cause of thymoma, a rare malignancy of thymic epithelial cells, is unknown. recent studies have reported the detection of dna from human t-cell lymphotropic virus type i (htlv-i) and human foamy virus (hfv) in small numbers of thymoma tumours, suggesting an aetiologic role for these retroviruses. in the present study, we evaluated 21 us thymoma patients and 20 patients with other cancers for evidence of infection with these viruses. we used the polymerase chain reaction to attempt to amplify ...	2004	15150553
transduction of long-term and mobilized peripheral blood-derived nod/scid repopulating cells by foamy virus vectors.	foamy virus (fv) vectors are a promising gene delivery system for use in hematopoietic stem cell gene therapy. previous fv vector marking studies in the nod/scid xenotransplantation model used umbilical cord blood (ucb)-derived scid repopulating cells (srcs) that were assayed 5-10 weeks posttransplantation. we now report efficient fv vector transduction (>65%) of ucb-derived primitive, long-term srcs engrafted for 18 weeks. in addition, we evaluated gene transfer into mobilized peripheral blood ...	2004	14965380
foamy viruses--a world apart.	foamy viruses (fvs) or spumaviruses were described for the first time in the early 1950s in cell cultures derived from monkey kidneys. later, fvs were isolated in several mammal species such as cats, cattle and horses. highly prevalent in non-human primates they are not naturally present in humans, although several cases of simian-to-human transmissions have been described. interestingly, the replication strategy of fvs differs in many aspects from that of other retroviruses, presenting features ...	2004	15358259
cell-cycle dependence of foamy virus vectors.	retroviruses differ in the extent to which they are dependent on host-cell proliferation for their replication, an aspect of their replication that impacts on their vector potential. foamy viruses offer distinct advantages over other retroviruses for development as vectors for gene therapy. a vector derived from the prototypic foamy virus (pfv), formerly known as human foamy virus (hfv), transduced aphidicolin-arrested cells five- to tenfold more efficiently than one derived from murine leukemia ...	2004	15448354
feline foamy virus tas protein is a dna-binding transactivator.	foamy viruses (fvs) harbour a transcriptional transactivator (tas) and two tas-responsive promoter regions, one in the 5' long terminal repeat (ltr) and the other an internal promoter (ip) in the envelope gene. to analyse the mechanism of transactivation of the fvs, the specificity of feline fv (ffv) tas protein, which is more distantly related to the respective proteins of non-human primate origin, were investigated. ffv tas has been shown specifically to activate gene expression from the cogna ...	2004	15448355
sensitive and specific detection of bovine immunodeficiency virus and bovine syncytial virus by 5' taq nuclease assays with fluorescent 3' minor groove binder-dna probes.	sensitive assays are required to detect bovine retroviruses in donor cattle used for the in vivo preparation of australian tick fever vaccines. 5' taq nuclease assays using 3' minor groove binder dna probes (taqman)mgb) were developed and compared to conventional pcr assays for the sensitive detection of bovine syncytial virus (bsv) and bovine immunodeficiency virus (biv). seven beef and dairy herds were screened to evaluate these tests. comparative sensitivities of pcr tests were determined by ...	2004	14715301
foamy virus integration.	it had been suggested that during integration of spumaretroviruses (foamy viruses) the right (u5) end of the cdna is processed, while the left (u3) remains uncleaved. we confirmed this hypothesis by sequencing two-long terminal repeat (ltr) circle junctions of unintegrated dna. based on an infectious foamy virus molecular clone, a set of constructs harboring mutations at the 5' end of the u3 region in the 3' ltr was analyzed for particle export, reverse transcription, and replication. following ...	2004	14963145
comparative functional characterization of the feline foamy virus transactivator reveals its species specificity.	foamy virus (fv) bel1/tas transactivators act as key regulators of gene expression and directly bind dna bel1 response elements (bres) in both the internal (ip) and 5'ltr promoters. here, we report the mapping and the virus species specificity of the nonhomologous feline foamy virus (ffv) bres in both promoters. the data indicate that ffv bel1 did not bind the primate fv ip.bre and that primate fv bel1 was not capable of binding the ffv ip.bre. in addition, we show that the c-terminal activation ...	2004	14972532
special coverage: 11th retroviruses conference. novel approaches to hiv vaccine are being studied. one possibility is vaccine that slows disease.	dozens of potential hiv vaccine candidates have been studied, and many of the latest additions include novel strategies to elicit hiv antibodies and cytotoxic t-cells, as well as some that may help slow disease progression. here's a look at some of the talk at the 11th conference on retroviruses and opportunistic infections.	2004	15074292
natural simian foamy virus infection in wild-caught gorillas, mandrills and drills from cameroon and gabon.	a survey for the presence of simian foamy retroviruses (sfvs) was performed in 44 wild-caught apes and monkeys, including 27 gorillas, 11 mandrills and six drills, originating from south cameroon or gabon. combined serological and/or nested-pcr assays indicated sfv infection among five gorilla gorilla gorilla, seven mandrillus sphinx and two mandrillus leucophaeus. sequences of a 425 bp fragment of the integrase gene were obtained for 11 animals. phylogenetic studies indicated that strains from ...	2004	15483245
characterization of the polymerase and rnase h activities of human foamy virus reverse transcriptase.	foamy virus (fv) replication, while related to that of orthoretroviruses, differs at a number of steps. several of these differences involve the reverse transcriptase (rt). there appear to be fewer rts present in fv than in orthoretroviruses; we previously proposed that the polymerase of fv rt was more active than orthoretroviral rts to compensate for the numerical difference. here we present further characterization of the rt of fv. the polymerase activity of fv rt was greater than that of huma ...	2004	15163704
simian retroviral infections in human beings.		2004	15246721
simian retroviral infections in human beings.		2004	15246722
role of the c terminus of foamy virus gag in rna packaging and pol expression.	foamy viruses (fv) are complex retroviruses that possess several unique features that distinguish them from all other retroviruses. fv gag and pol proteins are expressed independently of one another, and both proteins undergo single cleavage events. thus, the mature fv gag protein does not consist of the matrix, capsid, and nucleocapsid (nc) proteins found in orthoretroviruses, and the putative nc domain of fv gag lacks the hallmark cys-his motifs or i domains. as there is no gag-pol fusion prot ...	2004	15308736
coactivators p300 and pcaf physically and functionally interact with the foamy viral trans-activator.	foamy virus bel1/tas trans-activators act as key regulators of gene expression and directly bind to bel1 response elements (bre) in both the internal and the 5'ltr promoters leading to strong transcriptional trans-activation. cellular coactivators interacting with bel1/tas are unknown to date.	2004	15350211
persistent infection with primate foamy virus type 1 increases human immunodeficiency virus type 1 cell binding via a bet-independent mechanism.	we report that human t cells persistently infected with primate foamy virus type 1 (pfv-1) display an increased capacity to bind human immunodeficiency virus type 1 (hiv-1), resulting in increased cell permissiveness to hiv-1 infection and enhanced cell-to-cell virus transmission. this phenomenon is independent of hiv-1 receptor, cd4, and it is not related to pfv-1 bet protein expression. increased virus attachment is specifically inhibited by heparin, indicating that it should be mediated by in ...	2004	15452263
the phylogeography of orangutan foamy viruses supports the theory of ancient repopulation of sumatra.	phylogenetic analysis of foamy virus sequences obtained from bornean and sumatran orangutans showed a distinct clustering pattern. one subcluster was represented by both bornean and sumatran orangutan simian foamy viruses (sfv). combined analysis of host mitochondrial dna and sfv phylogeny provided evidence for the hypothesis of the repopulation of sumatra by orangutans from borneo.	2004	15507663
furin-mediated cleavage of the feline foamy virus env leader protein.	the molecular biology of spuma or foamy retroviruses is different from that of the other members of the retroviridae. among the distinguishing features, the n-terminal domain of the foamy virus env glycoprotein, the 16-kda env leader protein elp, is a component of released, infectious virions and is required for particle budding. the transmembrane protein elp specifically interacts with n-terminal gag sequences during morphogenesis. in this study, we investigate the mechanism of elp release from ...	2004	15564468
prototype foamy virus envelope glycoprotein leader peptide processing is mediated by a furin-like cellular protease, but cleavage is not essential for viral infectivity.	analogous to cellular glycoproteins, viral envelope proteins contain n-terminal signal sequences responsible for targeting them to the secretory pathway. the prototype foamy virus (pfv) envelope (env) shows a highly unusual biosynthesis. its precursor protein has a type iii membrane topology with both the n and c terminus located in the cytoplasm. coexpression of fv glycoprotein and interaction of its leader peptide (lp) with the viral capsid is essential for viral particle budding and egress. p ...	2004	15564494
ancient co-speciation of simian foamy viruses and primates.	although parasite-host co-speciation is a long-held hypothesis, convincing evidence for long-term co-speciation remains elusive, largely because of small numbers of hosts and parasites studied and uncertainty over rates of evolutionary change. co-speciation is especially rare in rna viruses, in which cross-species transfer is the dominant mode of evolution. simian foamy viruses (sfvs) are ubiquitous, non-pathogenic retroviruses that infect all primates. here we test the co-speciation hypothesis ...	2005	15772660
the requirements and mechanism for capsid assembly and budding of bovine foamy virus.	little is known about assembly of non-primate foamy virus (fv) such as bovine foamy virus (bfv). to help determine the requirements for assembly of bfv, we constructed bfv-gag expression plasmids containing all or part of the gag gene, with or without modification by addition of myristate (myr). each construct was transfected alone, and with pfenv, into sf-9 insect cells. the results showed that only the entire gag could transit through nucleus, which is required for bfv viral assembly in the cy ...	2005	15834655
characterization of env antigenicity of feline foamy virus (fefv) using fefv-infected cat sera and a monoclonal antibody.	to characterize neutralizing antigenicity in relation to env genotypes of feline foamy virus (fefv), serological analyses were performed using fefv-infected cat sera and several field isolates including two env genotypes (f17- and fuv-types). since three cats from which fefv were isolated were found to have undetectable titers of virus neutralization (vn) antibodies, even to the homologous virus, vn antibodies were further examined with complement supplementation as an enhancement factor. with t ...	2005	15778026
molecular biology. human rna slows down a primate retrovirus.		2005	15845813
a cellular microrna mediates antiviral defense in human cells.	in eukaryotes, 21- to 24-nucleotide-long rnas engage in sequence-specific interactions that inhibit gene expression by rna silencing. this process has regulatory roles involving micrornas and, in plants and insects, it also forms the basis of a defense mechanism directed by small interfering rnas that derive from replicative or integrated viral genomes. we show that a cellular microrna effectively restricts the accumulation of the retrovirus primate foamy virus type 1 (pfv-1) in human cells. pfv ...	2005	15845854
identification of domains in gag important for prototypic foamy virus egress.	sequence motifs (l domains) have been described in viral structural proteins. mutations in these lead to a defect at a late stage in virus assembly and budding. for several viruses, recruitment of an endosomal sorting complexes required for transport 1 subunit (tsg101), a component of the class e vacuolar protein sorting (evps) machinery, is a prerequisite for virion budding. to effect this, tsg101 interacts with the pt/sap l domain. we have identified candidate l-domain motifs, psap, pppi, and ...	2005	15858022
characterization of the functional domains of human foamy virus integrase using chimeric integrases.	retroviral integrases insert viral dna into target dna. in this process they recognize their own dna specifically via functional domains. in order to analyze these functional domains, we constructed six chimeric integrases by swapping domains between hiv-1 and hfv integrases, and two point mutants of hfv integrase. chimeric integrases with the central domain of hiv-1 integrase had strand transfer and disintegration activities, in agreement with the idea that the central domain determines viral d ...	2005	15879710
a novel function for spumaretrovirus integrase: an early requirement for integrase-mediated cleavage of 2 ltr circles.	retroviral integration is central to viral persistence and pathogenesis, cancer as well as host genome evolution. however, it is unclear why integration appears essential for retrovirus production, especially given the abundance and transcriptional potential of non-integrated viral genomes. the involvement of retroviral endonuclease, also called integrase (in), in replication steps apart from integration has been proposed, but is usually considered to be accessory. we observe here that integrati ...	2005	15904533
experimental therapy of allogeneic solid tumors induced in athymic mice with suicide gene-transducing replication-competent foamy virus vectors.	a replication competent foamy virus derived retroviral vector expressing suicide genes has been constructed and characterized in vitro. here we used vectors expressing the purine nucleoside phosphorylase (fov-7/pnp), the nitroreductase (fov-7/ntr), or the thymidine kinase (fov-7/tk) suicide gene in an in vivo athymic (nude) mice/human glioblastoma tumor model. gliomas were induced by subcutanous injection of u87 tumor cells. the virus vector was injected when the tumor became visible. mice with ...	2005	15905857
foamy virus bet proteins function as novel inhibitors of the apobec3 family of innate antiretroviral defense factors.	foamy viruses are a family of complex retroviruses that establish common, productive infections in a wide range of nonhuman primates. in contrast, humans appear nonpermissive for foamy virus replication, although zoonotic infections do occur. here we have analyzed the ability of primate and mouse apobec3g proteins to inhibit the infectivity of primate foamy virus (pfv) virions produced in their presence. we demonstrate that several apobec3 proteins can potently inhibit the infectivity of a pfv-b ...	2005	15994766
isolation of foamy viruses from peripheral blood lymphocytes.	the isolation of a retrovirus from peripheral blood lymphocytes/monocytes can be a difficult task, requiring the fulfillment of three essential parameters. first, this viral agent must infect such cells in vivo. second, these circulating cells should harbor wild-type proviruses. finally, the viral agent has to express, at least when these cells are cultured in vitro, the structural proteins necessary for the production of viral particles. foamy viruses (fvs), also known as spumaviruses, are comp ...	2005	16061971
quantification of hfv-integrated dna in human cells by alu-ltr real-time pcr.	integration is described as a key step in viral replication of all retroviruses. a sensitive and quantitative measure of an integrated molecule is a good way to examine the importance of the integration step and to evaluate efficiency of retroviral vectors for gene transfer or anti-integrase drugs. here, we report a sensitive and quantitative real-time polymerase chain reaction (pcr) technique to measure integrated viral dna in human cells during a foamy virus (hfv) infection. this technique is ...	2005	16061973
mucosal and systemic antibody responses in humans infected with simian foamy virus.	simian foamy virus (sfv) infection and the subsequent immune response are not well characterized. blood plasma, saliva, and urine were obtained from four humans and nine chimpanzees persistently infected with chimpanzee-type sfv for an unknown length of time. sfv-specific immunoglobulin g (igg) antibodies, but not iga antibodies, against the gag and bet proteins were detected, by western blotting, in all sample types from infected humans and chimpanzees. overall, chimpanzee samples had higher an ...	2005	16189020
characterization of prototype foamy virus gag late assembly domain motifs and their role in particle egress and infectivity.	foamy viruses (fv) are unusual among retroviruses since they require both gag and env structural proteins for particle egress. recently significant progress has been made towards the mechanistic understanding of the viral release process, in particular that of retroviruses, and the viral domains and cellular pathways involved. however little is currently known about domains of fv structural proteins and cellular proteins engaged in this process. by mutational analysis of sequence motifs in proto ...	2005	15827161
[comparison of several viral vectors for gene therapy of corneal endothelial cells].	in this paper we compare the transduction efficiency, toxicity, and safety of retroviral vectors [equine infectious anemia virus (eiav), human immunodeficiency virus-1 (hiv-1), human foamy virus (pfv] and adenovirus (ad) for potential use in gene therapy of corneal endothelial cells.	2005	15886987
rna and protein requirements for incorporation of the pol protein into foamy virus particles.	foamy viruses (fvs) generate their pol protein precursor molecule independently of the gag protein from a spliced mrna. this mode of expression raises the question of the mechanism of pol protein incorporation into the viral particle (capsid). we previously showed that the packaging of (pre)genomic rna is essential for pol encapsidation (m. heinkelein, c. leurs, m. rammling, k. peters, h. hanenberg, and a. rethwilm, j. virol. 76:10069-10073, 2002). here, we demonstrate that distinct sequences in ...	2005	15890940
protease-dependent uncoating of a complex retrovirus.	although retrovirus egress and budding have been partly unraveled, little is known about early stages of the replication cycle. in particular, retroviral uncoating, a process during which incoming retroviral cores are altered to allow the integration of the viral genome into host chromosomes, is poorly understood. to get insights into these early events of the retroviral cycle, we have used foamy complex retroviruses as a model. in this report, we show that a protease-defective foamy retrovirus ...	2005	15994819
determination of the relative amounts of gag and pol proteins in foamy virus particles.	we determined the relative ratios of gag and pol molecules in highly purified virions of spumaretroviruses or foamy viruses (fvs) using monoclonal antibodies and bacterially expressed reference proteins. we found that the cleaved p68gag moiety dominates in infectious fvs. furthermore, approximate mean ratios in fv are 16:1 (pr71gag plus p68gag:p85rt),12:1 (p68gag:p85rt), and 10:1 (pr71gag plus p68gag:p40in). thus, the results indicate that fvs have found a way to incorporate approximately as muc ...	2005	16004609
primate-to-human retroviral transmission in asia.	we describe the first reported transmission to a human of simian foamy virus (sfv) from a free-ranging population of nonhuman primates in asia. the transmission of an exogenous retrovirus, sfv, from macaques (macaca fascicularis) to a human at a monkey temple in bali, indonesia, was investigated with molecular and serologic techniques. antibodies to sfv were detected by western blotting of serum from 1 of 82 humans tested. sfv dna was detected by nested polymerase chain reaction (pcr) from the b ...	2005	16022776
the antiretroviral activity of apobec3 is inhibited by the foamy virus accessory bet protein.	genome hypermutation of different orthoretroviruses by cellular cytidine deaminases of the apobec3 family during reverse transcription has recently been observed. lentiviruses like hiv-1 have acquired proteins preventing genome editing in the newly infected cell. here we show that feline foamy virus (ffv), a typical member of the foamy retrovirus subfamily spumaretrovirinae, is also refractory to genome deamination. apobec3-like ffv genome editing in apobec3-positive feline crfk cells only occur ...	2005	15911774
rna interference: more than a research tool in the vertebrates' adaptive immunity.	in recent years, rna silencing, usage of small double stranded rnas of approximately 21 - 25 base pairs to regulate gene expression, has emerged as a powerful research tool to dissect the role of unknown host cell factors in this 'post-genomic' era. while the molecular mechanism of rna silencing has not been precisely defined, the revelation that small rna molecules are equipped with this regulatory function has transformed our thinking on the role of rna in many facets of biology, illustrating ...	2005	15916707
analysis and function of prototype foamy virus envelope n glycosylation.	the prototype foamy virus (pfv) glycoprotein, which is essential for pfv particle release, displays a highly unusual biosynthesis, resulting in posttranslational cleavage of the precursor protein into three particle-associated subunits, i.e., leader peptide (lp), surface (su), and transmembrane (tm). glycosidase digestion of metabolically labeled pfv particles revealed the presence of n-linked carbohydrates on all subunits. the differential sensitivity to specific glycosidases indicated that all ...	2005	15919919
efficient therapeutic gene expression in cultured rat hippocampal neurons mediated by human foamy virus vectors: a potential for the treatment of neurological diseases.	vectors derived from human foamy virus (hfv), with their nonpathogenic nature and a wide tissue tropism, have been successfully used as retroviral gene transfer vehicles. however, transduction of primary hippocampal neurons (hns) with hfv vectors has little been studied. to investigate the potential of hfv-derived vector in gene therapy for neurological diseases, efficient foreign gene expression in cultured rat hns was first demonstrated by successful enhanced green fluorescent protein (egfp) t ...	2005	15956801
ubiquitination of the prototype foamy virus envelope glycoprotein leader peptide regulates subviral particle release.	foamy virus (fv) particle egress is unique among retroviruses because of its essential requirement for gag and env coexpression for budding and particle release. the fv glycoprotein undergoes a highly unusual biosynthesis resulting in the generation of three particle-associated, mature subunits, leader peptide (lp), surface (su), and transmembrane (tm), derived from a precursor protein by posttranslational proteolysis mediated by furin or furinlike proteases. previously at least three lp product ...	2005	16306578
detection of antiviral antibodies using enzyme-linked immunosorbent assay.	following retroviral infection, specific antibodies against viral proteins may be detected in the blood, urine, milk, or saliva of an infected animal. enzyme-linked immunosorbent assay (elisa) is the most commonly used method to screen for antiviral antibodies, as the technique is sensitive, reproducible, relatively inexpensive, and easily adapted to large-scale screening. this chapter describes two independent elisa techniques. the first uses a recombinant biotinylated viral protein antigen exp ...	2005	16061982
construction and analysis of genomic, full-length infectious foamy virus dna clones.	the molecular engineering of recombinant plasmid dna clones containing the full-length and replication-competent feline foamy (retro)virus (ffv) proviral genome is described. the methods used to combine subgenomic ffv dna fragments can be applied to other retrovirus genomes, resulting in full-length, bacterially cloned retroviruses. in addition, techniques used to determine the replication competence of the cloned viral genomes are described. alternative technologies (not described here) are als ...	2005	16061994
molecular characterization of proteolytic processing of the gag proteins of human spumaretrovirus.	molecular characterization of proteolytic processing of the human spumaretrovirus (hsrv) gag proteins and the precise determination of cleavage sites was performed. for in vitro processing of recombinant hsrv gag proteins, a recombinant enzymatically active hsrv protease was employed. recombinant gag proteins and protease were cloned and expressed as hexa-histidine-tagged proteins in pet-32b and pet-22b vectors, respectively, in the e. coli bl21 expression strain. the recombinant proteins were p ...	2005	16061995
retroviral superinfection resistance.	the retroviral phenomenon of superinfection resistance (sir) defines an interference mechanism that is established after primary infection, preventing the infected cell from being superinfected by a similar type of virus. this review describes our present understanding of the underlying mechanisms of sir established by three characteristic retroviruses: murine leukaemia virus (mulv), foamy virus (fv), and human immunodeficiency virus (hiv). in addition, sir is discussed with respect to hiv super ...	2005	16107223
n-terminal gag domain required for foamy virus particle assembly and export.	among the retroviridae, foamy viruses (fvs) exhibit an unusual way of particle assembly and a highly specific incorporation of envelope protein into progeny virions. we have analyzed deletions and point mutants of the prototypic fv gag gene for capsid assembly and egress, envelope protein incorporation, infectivity, and ultrastructure. deletions introduced at the 3' end of gag revealed the first 297 amino acids (aa) to be sufficient for specific env incorporation and export of particulate materi ...	2005	16160174
inhibition of simian immunodeficiency virus by foamy virus vectors expressing sirnas.	viral vectors available for gene therapy are either inefficient or suffer from safety concerns for human applications. foamy viruses are non-pathogenic retroviruses that offer several unique opportunities for gene transfer in various cell types from different species. in this report, we describe the use of simian foamy virus type 1 (sfv-1) vector to examine the efficacy of therapeutic genes. hairpin short-interfering rna (sirna) that targets the simian immunodeficiency virus (siv) rev/env was pl ...	2005	16181654
amino acid preferences for a critical substrate binding subsite of retroviral proteases in type 1 cleavage sites.	the specificities of the proteases of 11 retroviruses representing each of the seven genera of the family retroviridae were studied using a series of oligopeptides with amino acid substitutions in the p2 position of a naturally occurring type 1 cleavage site (val-ser-gln-asn-tyr pro-ile-val-gln; the arrow indicates the site of cleavage) in human immunodeficiency virus type 1 (hiv-1). this position was previously found to be one of the most critical in determining the substrate specificity differ ...	2005	15767422
restriction of foamy viruses by apobec cytidine deaminases.	foamy viruses (fvs) are nonpathogenic retroviruses infecting many species of mammals, notably primates, cattle, and cats. we have examined whether members of the apolipoprotein b-editing catalytic polypeptide-like subunit (apobec) family of antiviral cytidine deaminases restrict replication of simian fv. we show that human apobec3g is a potent inhibitor of fv infectivity in cell culture experiments. this antiviral activity is associated with cytidine editing of the viral genome. both molecular f ...	2006	16378963
expanded tissue targets for foamy virus replication with simian immunodeficiency virus-induced immunosuppression.	foamy viruses (fv) are the oldest known genus of retroviruses and have persisted in nonhuman primates for over 60 million years. fv are efficiently transmitted, leading to a lifelong nonpathogenic infection. transmission is thought to occur through saliva, but the detailed mechanism is unknown. interestingly, this persistent infection contrasts with the rapid cytopathicity caused by fv in vitro, suggesting a host defense against fv. to better understand the tissue specificity of fv replication a ...	2006	16378969
role and mechanism of action of the apobec3 family of antiretroviral resistance factors.		2006	16414984
the dna-binding domain of the yeast spt10p activator includes a zinc finger that is homologous to foamy virus integrase.	the yeast spt10 gene encodes a putative histone acetyltransferase that binds specifically to pairs of upstream activating sequence (uas) elements found only in the histone gene promoters. here, we demonstrate that the dna-binding domain of spt10p is located between residues 283 and 396 and includes a his(2)-cys(2) zinc finger. the binding of spt10p to the histone uas is zinc-dependent and is disabled by a zinc finger mutation (c388s). the isolated dna-binding domain binds to single histone uas e ...	2006	16415340
foamy virus vector integration sites in normal human cells.	foamy viruses (fvs) or spumaviruses are retroviruses that have been developed as vectors, but their integration patterns have not been described. we have performed a large-scale analysis of fv integration sites in unselected human fibroblasts (n = 1,008) and human cd34(+) hematopoietic cells (n = 1,821) by using a bacterial shuttle vector and a comparable analysis of lentiviral vector integration sites in cd34(+) cells (n = 1,331). fv vectors had a distinct integration profile relative to other ...	2006	16428288
feline foamy virus-mediated marker gene transfer: identification of essential genetic elements and influence of truncated and chimeric proteins.	retroviral vectors derived from foamy or spumaretroviruses are considered promising tools for targeted gene delivery and vaccination purposes. in order to fully exploit this potential, we identified essential cis-acting sequences on the feline foamy virus (ffv) genome by constructing and analyzing a series of ffv-based replication-deficient vector genomes. cis-acting sequences essentially required for marker gene transfer were found to be localized at two sites on the ffv genome: (i) in the 5'-u ...	2006	16443252
detection and molecular characterization of foamy viruses in central african chimpanzees of the pan troglodytes troglodytes and pan troglodytes vellerosus subspecies.	foamy viruses are exogenous retroviruses that are highly endemic in non-human primates (nhps). recent studies, mainly performed in north america, indicated frequent simian foamy virus (sfv) infection in persons occupationally exposed to nhps. this zoonotic infection was demonstrated mainly after bites by chimpanzees [pan troglodytes (p. t.)] of the west african p. t. verus subspecies in primatology centers or zoos in the usa.	2006	16556292
genome-wide mapping of foamy virus vector integrations into a human cell line.	integration-site selection by retroviruses and retroviral vectors has gained increased scientific interest. foamy viruses (fvs) constitute a unique subfamily (spumavirinae) of the family retroviridae, for which the integration pattern into the human genome has not yet been determined. to accomplish this, 293 cells were transduced with fv vectors and the integration sites into the cellular genome were determined by a high-throughput method based on inverse pcr. for comparison, a limited number of ...	2006	16603537
modes of transmission and genetic diversity of foamy viruses in a macaca tonkeana colony.	background: foamy viruses are exogenous complex retroviruses that are highly endemic in several animal species, including monkeys and apes, where they cause persistent infection. simian foamy viral (sfv) infection has been reported in few persons occupationally exposed to non-human primates (nhp) in zoos, primate centers and laboratories, and recently in few hunters from central africa. most of the epidemiological works performed among nhp populations concern cross-sectional studies without long ...	2006	16608518
microbiology. bacterial bushwacking through a microtubule jungle.		2006	17095683
foamy virus infection in primates.	foamy viruses (fv), the oldest known genus of retroviridae, are unique among the retroviruses in having no disease association. it is not known why fv are non-pathogenic while infection by their closest relatives can be deadly. this may be related to the estimated 60 million years of coevolution of fv and their primate hosts. we review the current state of knowledge of fv infection, including information about the sites of viral replication and host immune responses, and discuss the role these m ...	2006	16872286
characterization of the prototype foamy virus envelope glycoprotein receptor-binding domain.	the foamy virus (fv) glycoprotein precursor gp130(env) undergoes a highly unusual biosynthesis, resulting in the generation of three particle-associated, mature subunits, leader peptide (lp), surface (su), and transmembrane (tm). little structural and functional information on the extracellular domains of fv env is available. in this study, we characterized the prototype fv (pfv) env receptor-binding domain (rbd) by flow cytometric analysis of recombinant pfv env immunoadhesin binding to target ...	2006	16873272
risk assessment: a model for predicting cross-species transmission of simian foamy virus from macaques (m. fascicularis) to humans at a monkey temple in bali, indonesia.	contact between humans and nonhuman primates (nhps) frequently occurs at monkey temples (religious sites that have become associated with free-ranging populations of nhps) in asia, creating the potential for nhp-human disease transmission. in march 2003 a multidisciplinary panel of experts participated in a workshop designed to model the risk of nhp-human pathogen transmission. the panel developed a risk assessment model to describe the likelihood of cross-species transmission of simian foamy vi ...	2006	16900504