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porcine endogenous retrovirus does not infect human cells using a bioartificial liver model system. 200111267509
valuation of transmission of porcine endogenous retrovirus into patients subjected to hemoperfusion using an extracorporeal bioartificial liver support system. 200111267594
heart valves from pigs and the porcine endogenous retrovirus: experimental and clinical data to assess the probability of porcine endogenous retrovirus infection in human subjects.replacement of heart valves in human subjects has become a routine procedure in cardiac operations. we sought to investigate whether commercially available glutaraldehyde-fixed porcine heart valve prostheses cause porcine endogenous retrovirus infection in human subjects because recent studies revealed that human cells can be infected with porcine endogenous retrovirus.200111279410
detection and characterization of porcine endogenous retrovirus in porcine plasma and porcine factor viii.the pig genome contains porcine endogenous retroviruses (pervs) capable of infecting human cells. detection of infectious retrovirus in porcine peripheral blood mononuclear cells and endothelial cells suggested to us that pig plasma is likely to contain perv. both perv env sequences and viral reverse transcriptase (rt) activity were detected in all plasma samples isolated from four nih minipigs. to detect infectious virus from plasma, we performed a culture assay using three cell lines of feline ...200111312325
sensitive and specific immunological detection methods for porcine endogenous retroviruses applicable to experimental and clinical xenotransplantation.the use of organs from transgenic pigs for xenotransplantation may be associated with the risk of transmission of microorganisms, especially when the transgenic pigs express human proteins influencing complement activation. the porcine endogenous retroviruses (pervs) are of particular concern as they can infect human cells in vitro. however, it is unknown whether pervs can infect transplant recipients in vivo and, if so, whether they are pathogenic. it is therefore essential for experimental and ...200111328583
lack of cross-species transmission of porcine endogenous retrovirus infection to nonhuman primate recipients of porcine cells, tissues, or organs.nonhuman primates (nhps) have been widely used in different porcine xenograft procedures inevitably resulting in exposure to porcine endogenous retrovirus (perv). surveillance for perv infection in these nhps may provide information on the risks of cross-species transmission of perv, particularly for recipients of vascularized organ xenografts for whom data from human clinical trials is unavailable.200111349732
comparison of replication-competent molecular clones of porcine endogenous retrovirus class a and class b derived from pig and human cells.vertically transmitted endogenous retroviruses pose an infectious risk in the course of pig-to-human transplantation of cells, tissues, and organs. two classes of polytropic type c porcine endogenous retroviruses (perv) which are infectious for human cells in vitro are known. recently, we described the cloning and characterization of replication-competent perv-b sequences from productively infected human cells (f. czauderna, n. fischer, k. boller, r. kurth, and r. r. tönjes, j. virol. 74:4028-40 ...200111356953
expression of porcine endogenous retrovirus in peripheral blood leukocytes from ten different breeds.the expression of porcine endogenous retroviruses (perv) was investigated in primary porcine peripheral blood leukocytes (pbl) of ten different pig breeds. the data suggest that perv exists in all porcine pbl. a new retroviral element, a foamy-like pol-related sequence, was also detected in pbl. three types of perv were detected in almost every animal. the breeding of perv-free pigs is likely to be difficult. further studies are required to assess the infectious disease risks associated with xen ...200011429004
porcine endogenous retrovirus is not transmitted in a discordant porcine-to-cynomolgus xenokidney transplantation model with long-term survival of organ recipients. 200010936401
analysis of potential porcine endogenous retrovirus transmission to baboon in vitro and in vivo. 200010936402
study of full-length porcine endogenous retrovirus genomes with envelope gene polymorphism in a specific-pathogen-free large white swine herd.specific-pathogen-free (spf) swine appear to be the most appropriate candidate for pig to human xenotransplantation. still, the risk of endogenous retrovirus transmission represents a major obstacle, since two human-tropic porcine endogenous retroviruses (pervs) had been characterized in vitro (p. le tissier, j. p. stoye, y. takeuchi, c. patience, and r. a. weiss, nature 389:681-682, 1997). here we addressed the question of perv distribution in a french large white spf pig herd in vivo. first, p ...200010954559
infection by porcine endogenous retrovirus after islet xenotransplantation in scid mice.animal donors such as pigs could provide an alternative source of organs for transplantation. however, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection. all pigs contain several copies of porcine endogenous retroviruses (perv), and at least three variants of perv can infect human cell lines in vitro in co-culture, infectivity and pseudotyping experiments. thus, if xenotransplantation of pig tissues results in perv viral replication, the ...200010993079
generation and testing of a highly specific anti-serum directed against porcine endogenous retrovirus nucleocapsid.advances in xenotransplantation offer chances to alleviate the shortage of human donor organs. the discovery that pig endogenous retroviruses (perv) can infect human cells in vitro has stimulated the discussion on infectious risk in xenotransplantation. a molecular and immunologic monitoring of xenograft recipients and of donor animals for putative infection with perv and other microorganisms is inevitable. in this report, we describe the generation and testing of a highly specific anti-serum di ...200011021668
xenotransplantation and the potential risk of xenogeneic transmission of porcine viruses.the clinical success of allotransplantation and the shortage of donor organs have led to a proposal for the use of animal organs as alternative therapeutic materials for humans. in that regard, swine are preferable to non-human primates as a source of donor organs. while applications for clinical trials for xenotransplantation have not yet been received in canada, several trials have already been authorized in the united states. a major concern, however, is the potential for xenogeneic transmiss ...200011041495
design and validation of immunological tests for the detection of porcine endogenous retrovirus in biological materials.the present study details the design and demonstrates function for a series of reagents and methods to allow the detection of exposure to antigens specific for porcine endogenous retrovirus (perv). the detection of perv is carried out by the means of a variety of immunological screening methods including, indirect immunofluorescence, western blotting and enzyme linked immunosorbent assay (elisa) for the detection of antibodies in serum specific for perv gag and env antigens. alternatively, perv- ...200011064112
no evidence for infection of human cells with porcine endogenous retrovirus (perv) after exposure to porcine fetal neuronal cells.recent demonstration of human cell infection in vitro with porcine endogenous retrovirus (perv) has raised safety concerns for new therapies that involve transplantation of pig cells or organs to humans. to assess better the specific risk that may be associated with the transplantation of fetal pig neuronal cells to the central nervous system of patients suffering from intractable neurologic disorders (parkinson's disease, huntington's disease, and epilepsy), we have performed studies to determi ...200011087157
mapping dispersed repetitive loci using semi-specific pcr cloning and somatic cell hybrid mapping.a simple and effective method based upon semi-specific pcr followed by cloning has been developed. chromosomal mapping of the generated fragment on a somatic cell hybrid panel identifies the chromosomal position, and yields a unique sequence tag for the site. using this method, the chromosomal location of one porcine endogenous retrovirus (perv) was determined. the porcine genomic sequences were first amplified by pcr using a perv-specific primer and a porcine short interspersed nuclear element ...200011095699
influence of human fulminant hepatic failure sera on endogenous retroviral expression in pig hepatocytes.a porcine endogenous retrovirus (perv) has been shown to infect human embryonic kidney 293 (hek293) cells in vitro. the perv proviral sequence exists in the genome of all porcine cells, including hepatocytes used in a bioartificial liver (bal). we examined the possibility of perv infection in hek293 cells during exposure to supernatant from cultured pig hepatocytes. pig hepatocytes were cultured in media supplemented with serum from patients in fulminant hepatic failure (fhf) to simulate conditi ...200010648582
liver allotransplantation after extracorporeal hepatic support with transgenic (hcd55/hcd59) porcine livers: clinical results and lack of pig-to-human transmission of the porcine endogenous retrovirus.whole organ extracorporeal perfusion of a genetically modified humanized (transgenic) pig liver has been proposed as a technology that may sustain patients with severe liver failure while awaiting human liver transplantation.200010670638
transplantation of embryonic porcine mesencephalic tissue in patients with pd.to assess the safety and the effect on standardized clinical rating measures of transplanted embryonic porcine ventral mesencephalic (vm) tissue in advanced pd.200010720272
establishment and characterization of molecular clones of porcine endogenous retroviruses replicating on human cells.the use of pig xenografts is being considered to alleviate the shortage of allogeneic organs for transplantation. in addition to the problems overcoming immunological and physiological barriers, the existence of numerous porcine microorganisms poses the risk of initiating a xenozoonosis. recently, different classes of type c porcine endogenous retoviruses (perv) which are infectious for human cells in vitro have been partially described. we therefore examined whether completely intact proviruses ...200010756014
pig endogenous retrovirus--a threat to clinical xenotransplantation?transplantation shows good results for patients with end-stage disease, but there is an increasing lack of organs. xenotransplantation, the transfer of live animal cells, tissues, or organs to another species, offers a potential solution to this shortfall. pig is regarded as the animal of choice for this purpose. meanwhile demonstration of pig endogenous retrovirus (perv) in all porcine herds has caused serious concern with respect to a possible transmission of the virus to humans with a transpl ...200010843410
a polymerase chain reaction-based protocol for the detection of transmission of pig endogenous retroviruses in pig to human xenotransplantation.xenotransplantation of pig organs and tissues to humans bears the risk of infection of immunosuppressed recipients by porcine endogenous retrovirus (perv) released from the transplanted tissue. however, when diagnosing potential perv transmission, it is essential to exclude microchimerism, i.e., persisting pig cells in analyzed bioptic material of xenotransplanted patients, which give rise to false positive perv signals. polymerase chain reaction (pcr) is so far the only suitable method to diagn ...200010852618
[clinical trials using cell xenografts. their place in the treatment of fulminant hepatitis].trials involving xenocells are mainly carried out in the context of treatment for acute liver failure. in fact, in this disease there is no accompanying chronic hepatopathy, and the liver has a significant potential for regeneration. regarding the clinical aspect, several trials have been conducted involving patients with severe liver failure awaiting hepatic transplantation. hepatic xenocells are the treatment of choice, as there is no normal human hepatocyte line available. hepatic xenocells o ...200010868409
no evidence of infection with porcine endogenous retrovirus in recipients of encapsulated porcine islet xenografts.transplantation of pig tissues into humans has the potential for cotransferring pig infections. knowledge of the epidemiology of pig infections transmissible to humans allows the development of risk limitation strategies at the source herd level, but potentially infectious pig endogenous retrovirus (perv) is ubiquitous in all domestic pigs and therefore is not avoidable. using a specific and sensitive rt-pcr and nested pcr for perv nucleic acids with primers, the screening of pigs from new zeala ...200011202575
extended analysis of the in vitro tropism of porcine endogenous retrovirus.we previously reported that mitogenic activation of porcine peripheral blood mononuclear cells resulted in production of porcine endogenous retrovirus(es) (perv[s]) capable of productively infecting human cells (c. wilson et al., j. virol. 72:3082-3087, 1998). we now extend that analysis to show that additional passage of isolated virus, named here perv-nih, through a human cell line yielded a viral population with a higher titer of infectious virus on human cells than the initial isolate. we sh ...200010590090
xenotransplantation.background: over the past 10 years xenotransplantation has generated much interest in the hope that it will enable us to overcome the current lack of human organ donors. this review examines the evolution and current therapeutic strategies that have been developed to overcome the predominant problem of graft rejection. methods: a literature review was undertaken using a medline search from january 1966 to august 1999. results and conclusion: despite the considerable advances that have been made ...199910594496
high throughput detection of retrovirus-associated reverse transcriptase using an improved fluorescent product enhanced reverse transcriptase assay and its comparison to conventional detection methods.the development and application of a novel, sensitive taqman fluorescent probe-based product enhanced rt test (f-pert) for the detection of retrovirus are described. the assay allows discrimination between the amplification signals generated by genuine positive signals that result from retroviral rt activity and the rt-like activity from dna polymerases. the rt-like activity from dna polymerases was suppressed by the addition of activated calf-thymus dna with no reduction in the rt activity. a l ...199910894635
porcine endogenous retrovirus is transmitted neither in vivo nor in vitro from porcine endothelial cells to baboons. 199910083401
development and validation of a western immunoblot assay for detection of antibodies to porcine endogenous retrovirus.reports that pig endogenous retrovirus (perv) infects human cells in vitro have heightened the importance of molecular and serologic monitoring of xenograft recipients for evidence of infection with perv. we report the development and validation of a perv-specific western immunoblot assay for the diagnostic testing of porcine xenografts recipients. this assay is based upon the serological cross-reactivity observed between perv variants capable of infecting human cells in vitro and other mammalia ...199910221475
transfer of porcine endogenous retrovirus across hollow fiber membranes: significance to a bioartificial liver.a porcine endogenous retrovirus (perv) capable of infecting human cells has been identified. this study was designed to determine whether hollow fiber membranes, such as those used in a bioartificial liver, block the transfer of perv.199910342317
polymerase chain reaction assays for the diagnosis of infection with the porcine endogenous retrovirus and the detection of pig cells in human and nonhuman recipients of pig xenografts.pigs offer an unlimited source of xenografts for humans. however, recipients of pig xenografts are inevitably exposed to the porcine endogenous retrovirus (perv), which is carried in the pig germline. the ability of perv to infect human cells in vitro has heightened safety concerns regarding the transmission of perv to pig xenograft recipients.199910440384
search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. the xen 111 study group.pig organs may offer a solution to the shortage of human donor organs for transplantation, but concerns remain about possible cross-species transmission of porcine endogenous retrovirus (perv). samples were collected from 160 patients who had been treated with various living pig tissues up to 12 years earlier. reverse transcription-polymerase chain reaction (rt-pcr) and protein immunoblot analyses were performed on serum from all 160 patients. no viremia was detected in any patient. peripheral b ...199910455044
evidence of absence of porcine endogenous retrovirus (perv) infection in patients treated with a bioartificial liver support system.porcine endogenous retrovirus (perv) genomes are present in all pig cells. in this retrospective study, we assessed perv infectivity in 28 patients treated with an extracorporeal bioartificial liver (hepatassist system) that includes a membrane device containing porcine hepatocytes. all patients tested negative for perv using polymerase chain reaction analysis of peripheral blood mononuclear cells (pbmc) collected up to 5 years after treatment. in vitro results showed that the membrane decreased ...199910491030
type c retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells.as part of the evaluation of porcine cells, tissues, and organs intended for transplantation into humans, we investigated the conditions required to induce expression and release of porcine endogenous retrovirus (poev) from primary cells. pigs contain endogenous retroviral sequences encoding infectious retrovirus, yet little is known about the conditions required to activate the expression and release of poev from primary cells. we show here that mitogenic activation of peripheral blood mononucl ...19989525633
identification of a full-length cdna for an endogenous retrovirus of miniature swine.endogenous retroviruses of swine are a concern in the use of pig-derived tissues for xenotransplantation into humans. the nucleotide sequence of porcine endogenous retrovirus taken from lymphocytes of miniature swine (perv-msl) has been characterized. perv-msl is a type c retrovirus of 8,132 bp with the greatest nucleic acid sequence identity to gibbon ape leukemia virus and murine leukemia virus. constitutive production of perv-msl rna has been detected in normal leukocytes and in multiple orga ...19989557749
porcine endogenous retrovirus (perv) was not transmitted from transplanted porcine endothelial cells to baboons in vivo.the discussion about the clinical risk of zoonoses in xenotransplantation has recently culminated in the demand for a moratorium on clinical organ transplantation using pig donors. the basis for this discussion was a recent report showing a possible trans-species transmission of pig endogenous retrovirus (perv) by in vitro transfer to human cell lines. at present, it remains unclear if this could also happen in vivo or in the setting of xenotransplantation. potential in vivo transfer of perv aft ...19989704386
expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells.the risk of interspecies transmission of retroviruses during xenotransplantation is suggested by reports of pig endogenous retrovirus (perv) released from porcine cell lines productively infecting human cell lines in vitro and of infectious perv being released from pig peripheral blood mononuclear cells after mitogenic stimulation. endothelial cells are the main interface between a xenograft and the recipient's leucocytes and tissues.19989728985
no evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts.the study of whether porcine xenografts can lead to porcine endogenous retrovirus (perv) infection of recipients is critical for evaluating the safety of pig-to-man xenotransplantation. perv is carried in the pig germline, and all recipients of porcine tissues or organs will be exposed to the virus.19989728986
detection of porcine endogenous retrovirus: possible involvement in pig islet xenotransplantation.one requirement prior to xenotransplantation of porcine islets during type 1 diabetes is to eliminate the risk of transmitting infectious agents, particularly retroviruses, even when specific pathogen-free (spf) pigs are used. we developed two sensitive complementary pcr-derived detection tests to assess this risk. this first is intended to detect a novel endogenous retrovirus pol sequence related to a recently described human endogenous retrovirus (herv-l) and to foamy retroviruses. primers for ...19989881242
bortezomib, c1-inhibitor and plasma exchange do not prolong the survival of multi-transgenic galt-ko pig kidney xenografts in baboons.galactosyl-transferase ko (galt-ko) pigs represent a potential solution to xenograft rejection, particularly in the context of additional genetic modifications. we have performed life supporting kidney xenotransplantation into baboons utilizing galt-ko pigs transgenic for human cd55/cd59/cd39/ht. baboons received tacrolimus, mycophenolate mofetil, corticosteroids and recombinant human c1 inhibitor combined with cyclophosphamide or bortezomib with or without 2-3 plasma exchanges. one baboon recei ...025612490
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