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 ... | 1998 | 9525633 |
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 ... | 1998 | 9557749 |
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 ... | 1998 | 9704386 |
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. | 1998 | 9728985 |
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. | 1998 | 9728986 |
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 ... | 1998 | 9881242 |
porcine endogenous retrovirus is transmitted neither in vivo nor in vitro from porcine endothelial cells to baboons. | | 1999 | 10083401 |
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 ... | 1999 | 10221475 |
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. | 1999 | 10342317 |
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. | 1999 | 10440384 |
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 ... | 1999 | 10455044 |
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 ... | 1999 | 10491030 |
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 ... | 2000 | 10590090 |
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 ... | 1999 | 10594496 |
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 ... | 2000 | 10648582 |
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. | 2000 | 10670638 |
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. | 2000 | 10720272 |
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 ... | 2000 | 10756014 |
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 ... | 2000 | 10843410 |
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 ... | 2000 | 10852618 |
[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 ... | 2000 | 10868409 |
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 ... | 1999 | 10894635 |
porcine endogenous retrovirus is not transmitted in a discordant porcine-to-cynomolgus xenokidney transplantation model with long-term survival of organ recipients. | | 2000 | 10936401 |
analysis of potential porcine endogenous retrovirus transmission to baboon in vitro and in vivo. | | 2000 | 10936402 |
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 ... | 2000 | 10954559 |
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 ... | 2000 | 10993079 |
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 ... | 2000 | 11021668 |
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 ... | 2000 | 11041495 |
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- ... | 2000 | 11064112 |
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 ... | 2000 | 11087157 |
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 ... | 2000 | 11095699 |
susceptibility of the porcine endogenous retrovirus to reverse transcriptase and protease inhibitors. | porcine xenografts may offer a solution to the shortage of human donor allografts. however, all pigs contain the porcine endogenous retrovirus (perv), raising concerns regarding the transmission of perv and the possible development of disease in xenotransplant recipients. we evaluated 11 antiretroviral drugs licensed for human immunodeficiency virus type 1 (hiv-1) therapy for their activities against perv to assess their potential for clinical use. fifty and 90% inhibitory concentrations (ic(50) ... | 2001 | 11134319 |
evidence of porcine endogenous retroviruses in porcine factor viii and evaluation of transmission to recipients with hemophilia. | since 1984, unheated porcine clotting factor viii (hyate:c) has been used to treat severe bleeding episodes in persons with hemophilia who have antibodies to human clotting factor. we document the presence of porcine endogenous retrovirus (perv) in plasma samples of pigs and in clinical lots of hyate:c. both gag and pol perv rna sequences were detected by reverse-transcriptase (rt) polymerase chain reaction in 13 of 13 lots of hyate:c tested. among 10 of these lots, rt activity also was detected ... | 2001 | 11170992 |
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 ... | 2000 | 11202575 |
identification of novel porcine endogenous betaretrovirus sequences in miniature swine. | pcr amplification of genomic dna from miniature swine peripheral blood lymphocytes, using primers corresponding to highly conserved regions of the polymerase (pol) gene, allowed the identification of two novel porcine endogenous retrovirus (perv) sequences, pmsn-1 and pmsn-4. phylogenetic analyses of the nucleotide sequences of pmsn-1 and pmsn-4 revealed them to be most closely related to betaretroviruses. the identification of pervs belonging to the betaretrovirus genus shows that endogenous re ... | 2001 | 11222699 |
multiple groups of novel retroviral genomes in pigs and related species. | in view of the concern over potential infection hazards in the use of porcine tissues and organs for xenotransplantation to humans, we investigated the diversity of porcine endogenous retrovirus (perv) genomes in the dna of domestic pigs and related species. in addition to the three known envelope subgroups of infectious gamma retroviruses (perv-a, -b, and -c), classed together here as perv group gamma 1, four novel groups of gamma retrovirus (gamma 2 to gamma 5) and four novel groups of beta re ... | 2001 | 11222700 |
monitoring xenotransplant recipients for infection by perv. | concerns have been raised over the possibility of transmission of porcine endogenous retrovirus (perv) to porcine xenograft recipients. | 2001 | 11239511 |
porcine endogenous retroviruses: in vitro host range and attempts to establish small animal models. | using transgenic pigs as the source of cells or organs for xenotransplantation is associated with the risk of porcine endogenous retrovirus (perv) transmission. multiple proviruses are integrated into the genome of all pigs, and virus particles, some of which are able to infect human cells, are released from normal pig cells. in order to evaluate the potential risk posed by the transmission of pervs, in vitro infection studies were performed as a basis for small animal as well as non-human prima ... | 2001 | 11257189 |
analysis of potential porcine endogenous retrovirus (perv) transmission in a whole-organ xenotransplantation model without interfering microchimerism. | the question whether porcine xenografts can lead to porcine endogenous retrovirus (perv) infection of recipients is critical for the evaluation of the safety of pig-to-man xenotransplantation. unfortunately, polymerase chain reaction (pcr)-based analysis of potential perv infections in nonhuman-primate whole-organ xenotransplantation models is hampered by false positive results due to chimeric porcine cells. to avoid the inherent analytical problem of xenomicrochimerism, we developed a non-life- ... | 2001 | 11263553 |
altered infectivity of porcine endogenous retrovirus by "protective" avian antibodies: implications for pig-to-human xenotransplantation. | | 2001 | 11267019 |
porcine endogenous retrovirus does not infect human cells using a bioartificial liver model system. | | 2001 | 11267509 |
valuation of transmission of porcine endogenous retrovirus into patients subjected to hemoperfusion using an extracorporeal bioartificial liver support system. | | 2001 | 11267594 |
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. | 2001 | 11279410 |
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 ... | 2001 | 11312325 |
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 ... | 2001 | 11328583 |
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. | 2001 | 11349732 |
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 ... | 2001 | 11356953 |
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 ... | 2000 | 11429004 |
the number of a u3 repeat box acting as an enhancer in long terminal repeats of polytropic replication-competent porcine endogenous retroviruses dynamically fluctuates during serial virus passages in human cells. | the organization and transcriptional regulation of porcine endogenous retrovirus (perv) long terminal repeats (ltrs) are unknown. we have studied the activity of ltrs from replication-competent molecular clones by performing luciferase reporter assays. the ltrs differ in the presence and number of 39-bp repeats located in u3 that confer strong promoter activity in human, simian, canine, feline, and porcine cell lines, whereas for ltrs devoid of the repeats, the promoter strength was significantl ... | 2001 | 11435573 |
the porcine endogenous retrovirus long terminal repeat contains a single nucleotide polymorphism that confers distinct differences in estrogen receptor binding affinity between perv a and perv b/c subtypes. | porcine endogenous retroviruses (perv) have been shown to have zoonotic potential, both in vitro and in vivo. once integrated into the host cell genome activation of the proviral genes is ultimately dependent upon transactivation of the long terminal repeat (ltr). currently there is no direct evidence of host cell transcription factors interacting with perv ltrs. using comparative genomics we discovered a potentially functional single nucleotide polymorphism (snp) within the u5 region downstream ... | 2001 | 11448161 |
identification of a novel type c porcine endogenous retrovirus: evidence that copy number of endogenous retroviruses increases during host inbreeding. | different classes of porcine endogenous retroviruses (pervs), which have the potential to infect humans during xenotransplantation, have been isolated from the pig genome. because vertebrate genomes may contain numerous endogenous retrovirus sequences, the pig genome was examined for additional endogenous retroviruses, resulting in the isolation of a novel, complete endogenous retrovirus genome, designated perv-e. the gag, pol and env genes of perv-e are closely related to those of human endogen ... | 2001 | 11457988 |
characterization of a porcine lung epithelial cell line suitable for influenza virus studies. | we established a porcine lung epithelial cell line designated st. jude porcine lung cells (sjpl) and demonstrated that all tested influenza a and b viruses replicated in this cell line. the infectivity titers of most viruses in sjpl cells were comparable to or better than those in mdck cells. the propagation of influenza viruses from clinical samples in sjpl cells did not lead to antigenic changes in the hemagglutinin molecule. the numbers of both sia2-3gal and sia2-6gal receptors on sjpl cells ... | 2001 | 11533214 |
mapping full-length porcine endogenous retroviruses in a large white pig. | xenotransplantation may bridge the widening gap between the shortage of donor organs and the increasing number of patients waiting for transplantation. however, a major safety issue is the potential cross-species transmission of porcine endogenous retroviruses (perv). this problem could be resolved if it is possible to produce pigs that do not contain replication-competent copies of this virus. in order to determine the feasibility of this, we have determined the number of potentially replicatio ... | 2001 | 11711616 |
porcine endogenous retroviruses (pervs): generation of specific antibodies, development of an immunoperoxidase assay (ipa) and inhibition by azt. | xenotransplantation may be associated with the risk of transmission of microorganisms. in particular, the porcine endogenous retroviruses (perv) have raised concerns as in vitro experiments show susceptibility of human cells for perv infection. however, it remains unclear whether pervs are able to infect transplant recipients in vivo and whether they are pathogenic. it is therefore essential that the risks are evaluated and for this purpose specific and sensitive screening methods for pervs have ... | 2001 | 11737857 |
in vivo analysis of porcine endogenous retrovirus expression in transgenic pigs. | xenotransplantation offers a potential solution to the shortage of donor organs for allotransplantation. in vitro studies that demonstrate the transmission of porcine endogenous retroviruses (perv) from porcine cells to human cells and cell lines have raised concerns regarding the potential transmission of perv to both xenograft recipients and their contacts (1-4). while no evidence of infection has been detected in any patients who have been treated with a variety of different porcine tissues ( ... | 2001 | 11773903 |
human cd59 incorporation into porcine endogenous retrovirus particles: implications for the use of transgenic pigs for xenotransplantation. | transgenic pigs have been engineered to express human cd59 (hcd59) in order to suppress hyperacute rejection of xenotransplants in human recipients. in this study, porcine endogenous retrovirus (perv) was produced in a porcine cell line expressing hcd59 in order to examine the effect of this complement control protein on perv neutralization by human sera. hcd59 was found to be incorporated into perv particles produced from engineered st-iowa cells. perv incorporation of hcd59 resulted in a drama ... | 2002 | 11799196 |
porcine endogenous retrovirus transmission characteristics of an inbred herd of miniature swine. | here we report the identification of inbred miniature swine that failed to produce human-tropic replication-competent porcine endogenous retroviruses (htrc pervs), using in vitro coculture assays. when htrc pervs were isolated from transmitting animals, all were recombinant viruses, with the receptor-binding domain of perv-a combining with perv-c-related sequences. | 2002 | 11861871 |
clinical and laboratory evaluation of the safety of a bioartificial liver assist device for potential transmission of porcine endogenous retrovirus. | the potential risk of transmission of porcine endogenous retroviruses (perv) from xenogeneic donors into humans has been widely debated. because we were involved in a phase i/ii clinical trial using a bioartificial liver support system (blss), we proceeded to evaluate the biosafety of this device. | 2002 | 11884940 |
productive infection of a mink cell line with porcine endogenous retroviruses (pervs) but lack of transmission to minks in vivo. | porcine endogenous retroviruses (pervs) are considered a special risk for xenotransplantation because they are an integral part of the porcine genome and are able to infect cells of numerous species including humans in vitro. among these cells, the mink lung epithelial cell line mv1lu could be productively infected with perv. provirus integration was detected by pcr, expression of viral proteins was shown by immunostaining and reverse transcriptase was detected in cell supernatants. perv produce ... | 2002 | 11890525 |
development and perspectives of bioartificial liver support. | bioartificial liver support systems containing adsorbent devices, xenogeneic whole liver perfusion, and hybrid bioartificial liver are anticipated to be effective for the treatment of severe hepatic failure. at present, whole liver perfusion and the hybrid bioartificial liver are two mainstreams in the field of the bioartificial liver, but it is still unclear whether either of them has significant beneficial effects in hepatic failure patients. we developed a new system of xenogeneic direct hemo ... | 2002 | 11941991 |
molecular and enzymatic characterization of the porcine endogenous retrovirus protease. | the protease of the porcine endogenous retrovirus (perv) subtypes a/b and c was recombinantly expressed in escherichia coli as proteolytically active enzyme and characterized. the perv gag precursor was also recombinantly produced and used as the substrate in an in vitro enzyme assay in parallel with synthetic nonapeptide substrates designed according to cleavage site sequences identified in the perv gag precursor. the proteases of all perv subtypes consist of 127 amino acid residues with an m(r ... | 2002 | 12097607 |
microchimerism and transmission of porcine endogenous retrovirus from a pig cell line or specific pathogen-free pig islets to mouse tissues and human cells during xenografts in nude mice. | pig islets could transmit porcine endogenous retroviruses (perv) to diabetic patients. our previous work showed that pig islets expressed low levels of perv mrna and were not likely to transmit perv to human cells in vitro. the real risk of infection during pig tissue xenografts can only be evaluated by in vivo experiments. | 2002 | 12107737 |
virus safety in xenotransplantation: first exploratory in vivo studies in small laboratory animals and non-human primates. | for xenotransplantation, the transplantation of animal cells, tissues and organs into human recipients, to date, pigs are favored as potential donors. beside ethical, immunological, physiological and technical problems, the microbiological safety of the xenograft has to be guaranteed. it will be possible to eliminate all of the known porcine microorgansims in the nearby future by vaccinating or specified pathogen-free breeding. thus, the main risk will come from the porcine endogenous retrovirus ... | 2002 | 12180842 |
pcr-based cloning and immunocytological titration of infectious porcine endogenous retrovirus subgroup a and b. | two pig endogenous retroviruses (perv), perv-a and -b, productively infect human cells and are therefore considered to constitute a potential risk in pig-to-human xenotransplantation. a pcr-based cloning technique to isolate infectious perv proviruses was established. overlapping 3' half and 5' halves of perv proviral genomes were amplified using dna extracted from human 293 cells infected with perv-a or -b. these clones were fused at a unique restriction site in the overlapping region and teste ... | 2002 | 12185278 |
development of a real time quantitative pcr assay for detection of porcine endogenous retrovirus. | real time pcr technology was applied to the development of assays for detection and quantitation of porcine endogenous retrovirus (perv) rna and dna sequences in tissues and cells of human or animal origin. a plasmid construct encoding the perv-pol gene or the in vitro transcribed rna derived from the plasmid (crna) serves as a standard template for amplification of a 178 bp fragment. this study showed that the detection of this target sequence was linear over a range from 20 copies to 2 million ... | 2002 | 12367734 |
porcine endogenous retrovirus--advances, issues and solutions. | | 2002 | 12371932 |
porcine endogenous retrovirus infects but does not replicate in nonhuman primate primary cells and cell lines. | porcine endogenous retroviruses (perv) can infect human cell lines in vitro; hence, there is a presumed risk of viral exposure to a recipient when pig cells are transplanted into humans (xenotransplantation). nonhuman primates (nhp) are considered a potential permissive animal model to study the risk of in vivo infection of perv after xenotransplantation. we set out to determine whether perv can infect and replicate in nhp primary cells or established cell lines from african green monkey, rhesus ... | 2002 | 12388691 |
characterization of porcine endogenous retrovirus gamma pro-pol nucleotide sequences. | endogenous retroviral sequences in the pig genome (perv) represent a potential infectious risk in xenotransplantation. all known infectious perv have been asssigned to the perv gamma1 family, consisting of the subfamilies a, b, and c. the aim of the study was the concise examination of perv gamma by the analysis of the retroviral pro-pol sequences. the analysis of 52 pro-pol clones amplified in this study revealed eight perv gamma families. in addition to four already-described families (gamma1, ... | 2002 | 12388734 |
case-control study on the association of porcine circovirus type 2 and other swine viral pathogens with postweaning multisystemic wasting syndrome. | a field-based case-control study was conducted to assess the strength of association of porcine circovirus type 2 (pcv2) and some major swine viruses with postweaning multisystemic wasting syndrome (pmws). cases were defined as individual pigs with a clinical history of progressive weight loss and histopathological lesions characteristic of pmws. controls were pigs without clinical signs and histopathological lesions typical of pmws. a total of 31 cases and 56 controls was identified from diagno ... | 2002 | 12423025 |
transcriptional regulation of porcine endogenous retroviruses released from porcine and infected human cells by heterotrimeric protein complex nf-y and impact of immunosuppressive drugs. | recent studies revealed a significant promoter activity of porcine endogenous retrovirus (perv) long terminal repeats (ltrs) in different human and mammalian cell lines, which is mediated by a 39-bp repeat located in the u3 region in different numbers, representing an enhancer (g. scheef, n. fischer, u. krach, and r. r. tönjes, j. virol. 75:6933-6940, 2001). a statistical transcription factor analysis revealed putative binding sites for the ccaat-binding transcription factor nf-y inside the 39-b ... | 2002 | 12438581 |
sequence analysis of porcine endogenous retrovirus long terminal repeats and identification of transcriptional regulatory regions. | porcine cells express endogenous retroviruses, some of which are infectious for human cells. to better understand the replication of these porcine endogenous retroviruses (pervs) in cells of different types and animal species, we have performed studies of the long terminal repeat (ltr) region of known gammaretroviral isolates of perv. nucleotide sequence determination of the ltrs of perv-nih, perv-c, perv-a, and perv-b revealed that the perv-a and perv-b ltrs are identical, whereas the perv-nih ... | 2003 | 12477819 |
differences in release and determination of subtype of porcine endogenous retroviruses produced by stimulated normal pig blood cells. | porcine endogenous retroviruses (pervs) are of particular concern with xenotransplantations using pig cells, tissues or organs as they are present in the genome of all pig strains and are able to infect human cells in vitro. however, it remains unclear whether perv particles will be produced in vivo and whether they may infect xenotransplant recipients. since normal pig peripheral blood mononuclear cells (pbmcs) may be transmitted together with the transplanted organ, the production of pervs by ... | 2003 | 12566695 |
susceptibility of recombinant porcine endogenous retrovirus reverse transcriptase to nucleoside and non-nucleoside inhibitors. | transplantation of organs, tissues or cells from pigs to humans could be a potential solution to the shortage of human organs for transplantation. porcine endogenous retroviruses (pervs) remain a major safety concern for porcine xenotransplantation. thus, finding drugs that could be used as virological prophylaxis (or therapy) against perv replication would be desirable. one of the most effective ways to block retroviral multiplication is to inhibit the enzyme reverse transcriptase (rt) which ca ... | 2002 | 12568344 |
a primary screening of porcine endogenous retrovirus in some chinese pigs. | | 2003 | 12591523 |
bioartificial liver support anno 2001. | despite maximal intensive care, mortality of acute fulminant hepatic failure is high: 60%-75% in several studies. in addition patients with chronic liver insufficiency suffer from a bad quality of life: all patients suffer from fatigue; symptoms of hepatic encephalopathy, jaundice, and itching are often present. analogous to artificial kidney treatment in patients with renal failure, an artificial liver assist device is needed not only to bridge patients with fulminant hepatic failure to liver t ... | 2002 | 12602524 |
expression and characterization of a recombinant novel reverse transcriptase of a porcine endogenous retrovirus. | the study of porcine endogenous retroviruses (pervs) becomes increasingly important due to the potential use of pig cells, tissues, and organs as a source for xenogenic cell therapy and xenotransplantation into humans. consequently, we have constructed a plasmid that induces in bacteria the synthesis of a soluble and highly active reverse transcriptase (rt) of perv-b. the purified perv rt was studied biochemically in comparison with the rt of murine leukemia virus (mlv), because of the high-sequ ... | 2003 | 12667803 |
neutralizing antibodies against conserved domains of p15e of porcine endogenous retroviruses: basis for a vaccine for xenotransplantation? | porcine xenotransplants may offer a potential solution to the problem posed by the limited supply of allotransplants. however, xenotransplantation may be associated with the risk of transmission of microorganisms, in particular of porcine endogenous retroviruses (pervs) that are an integral part of the porcine genome and able to infect human cells in vitro. possible strategies to prevent virus transmission include the development of perv knockout animals or of effective vaccines. when antisera p ... | 2003 | 12667808 |
ultra-sensitive and specific detection of porcine endogenous retrovirus (perv) using a sequence-capture real-time pcr approach. | use of porcine xenografts presents as a possible solution to the current shortage of human allografts limiting transplantation procedures. while no definitive observation of in vivo porcine endogenous retrovirus (perv) transmission in humans has been reported, the in vitro ability of perv to infect human cells and the observation of perv transmission to immunodeficient mice suggest a need for ultra-sensitive techniques to monitor porcine xenograft recipients and contacts for possible perv transm ... | 2003 | 12711065 |
identification of receptors for pig endogenous retrovirus. | xenotransplantation of porcine tissues has the potential to treat a wide variety of major health problems including organ failure and diabetes. balanced against the potential benefits of xenotransplantation, however, is the risk of human infection with a porcine microorganism. in particular, the transmission of porcine endogenous retrovirus (perv) is a major concern [chapman, l. e. & bloom, e. t. (2001) j. am. med. assoc. 285, 2304-2306]. here we report the identification of two, sequence-relate ... | 2003 | 12740431 |
detection of porcine endogenous retrovirus in cultures of freshly isolated porcine bone marrow cells. | pigs are under consideration as possible sources of organs for xenotransplantation in humans. the induction of hematopoietic microchimerism through xenotransplantation of source animal hematopoietic cells has been suggested as a means to induce tolerance in potential recipients. because all porcine cells contain genetic information for porcine endogenous retrovirus (perv), coculture techniques, reverse transcriptase (rt) and reverse transcriptase-polymerase chain reaction assays were used to det ... | 2003 | 12795682 |
inactivation of porcine endogenous retrovirus by human serum as a function of complement activated through the classical pathway. | background: the clinical use of organs and cells of pig donors as a source of tissue for xenotransplantation and extracorporeal therapies has been problematic due to the risk for zoonotic infection of porcine endogenous retroviruses (perv). methods: the effect of human serum on perv was evaluated using an infectivity assay and virolysis assay. cell-free perv infection to human 293 cells was determined by the presence of proviruses 5 days post-infection by a highly sensitive nested pcr, and the l ... | 2003 | 12809937 |
xenoreactive anti-galalpha(1,3)gal antibodies prevent porcine endogenous retrovirus infection of human in vivo. | the discovery of porcine endogenous retroviruses (perv) has raised concerns regarding the safety of pig to human xenotransplantation. in this study, we examined perv infection of human cells in vivo. furthermore, we examined the effect of human xenoreactive natural antibody on in vivo perv infection. human peripheral blood leukocyte reconstituted severe combined immunodeficiency mice were transplanted with porcine aortic endothelial cells (paec). perv gene expression was readily detected in huma ... | 2003 | 12826373 |
characterization of two porcine endogenous retrovirus integration loci and variability in pigs. | the pig (sus scrofa) is a potential organ donor for man but porcine endogenous retroviruses (pervs) represent an important concern for patients, and identification or engineering of perv-free pigs suitable for xenotransplantation is a major undertaking. consequently, studies of variability in pigs for the presence of pervs at specific loci are a prerequisite. we identified genomic flanking sequences of two pervs cloned in bacterial artificial chromosomes, a replication-competent perv-a at locus ... | 2003 | 12827326 |
detection of porcine endogenous retrovirus (perv) using highly specific antisera against gag and env. | porcine endogenous retroviruses (perv) are considered an obstacle to the safe use of cells, tissues, and organs from pigs in the course of xenotransplantation. thus, the detection of viral proteins and of a potential perv infection is of major interest. recently, we have published the generation of a highly specific antiserum directed against the nucleocapsid (p10) of perv (xenotransplantation 7 (2000), 221). here we present new peptide-antisera specific to the capsid protein (p30) and the surfa ... | 2003 | 12832219 |
packaging of human endogenous retrovirus sequences is undetectable in porcine endogenous retrovirus particles produced from human cells. | the chronic shortage of human donor organs and tissues for allotransplantation could be relieved if clinical xenotransplantation were to become a viable clinical therapy. balanced against the benefits of xenotransplantation are the possible consequences of zoonotic infections, and in particular, infection by porcine endogenous retrovirus (perv). an often-proclaimed risk of perv infection is the possible recombination of perv with human endogenous retroviruses (herv). to address this issue, we ex ... | 2003 | 12919738 |
xenotransplantation and pig endogenous retroviruses. | xenotransplantation, in particular transplantation of pig cells, tissues and organs into human patients, may alleviate the current shortage of suitable allografts available for human transplantation. this overview addresses the physiological, immunological and virological factors considered with regard to xenotransplantation. among the issues reviewed are the merits of using pigs as xenograft source species, the compatibility of pig and human organ physiology and the immunological hindrances wit ... | 2003 | 12931341 |
[analysis of subtype of porcine endogenous retrovirus in two species of chinese pigs]. | to analyze the subtype of porcine endogenous retrovirus (perv) in two species of chinese pigs-wu zhishan pig and banna minipig inbred; the total number of pigs being eighty six. | 2003 | 12947687 |
porcine endogenous retroviruses: no infection in patients treated with a bioreactor based on porcine liver cells. | acute liver failure (alf) remains a disease with high mortality. bioartificial liver support systems, which combine living cells of the liver in an extracorporeal circuit, have been successfully used in first clinical trials. the shortage of human organs to be used for bioreactors and the lack of safe and effective human liver cell lines have resulted in pigs becoming an important hepatic cell source. however, using these cells may be associated with the risk of transmission of porcine endogenou ... | 2003 | 12957184 |
in vivo model for cross-species porcine endogenous retrovirus transmission using tissue engineered pulmonary arteries. | acellularised porcine scaffolds have been successfully used for cardiovascular tissue engineering. however, there is concern about the possibility of porcine endogenous retrovirus (perv) transmission. in this study we developed an in vivo model for cross-species perv transmission. | 2003 | 12965305 |
genetic alterations of the long terminal repeat of an ecotropic porcine endogenous retrovirus during passage in human cells. | human-tropic porcine endogenous retroviruses (perv) such as perv-a and perv-b can infect human cells and are therefore a potential risk to recipients of xenotransplants. a similar risk is posed by recombinant viruses containing the receptor-binding site of perv-a and large parts of the genome of the ecotropic perv-c including its long terminal repeat (ltr). we describe here the unique organization of the perv-c ltr and its changes during serial passage of recombinant virus in human cells. an inc ... | 2003 | 14517066 |
acellularized porcine heart valve scaffolds for heart valve tissue engineering and the risk of cross-species transmission of porcine endogenous retrovirus. | acellularized porcine heart valve scaffolds have been successfully used for heart valve tissue engineering, creating living functioning heart valve tissue. however, there is concern about the possibility of porcine endogenous retrovirus transmission. in this study we investigated whether acellularized porcine heart valve scaffold causes cross-species transmission of porcine endogenous retrovirus in a sheep model. | 2003 | 14566238 |
bridging a patient with acute liver failure to liver transplantation by the amc-bioartificial liver. | recently a phase i clinical trial has been started in italy to bridge patients with acute liver failure (alf) to orthotopic liver transplantation (olt) by the amc-bioartificial liver (amc-bal). the amc-bal is charged with 10 x 10(9) viable primary porcine hepatocytes isolated from a specified pathogen-free (spf) pig. here we report a patient with alf due to acute hbv infection. this patient was treated for 35 h by two amc-bal treatments and was bridged to olt. there was improvement of biochemica ... | 2003 | 14579924 |
intracellularly expressed single-domain antibody against p15 matrix protein prevents the production of porcine retroviruses. | the presence of porcine endogenous retroviruses presents a potential risk of transmission of infectious diseases (xenozoonosis) if tissues and organs from genetically modified pigs are to be used in xenotransplantation. here, we report that intracellular expression of a llama single-domain antibody against p15, the matrix domain protein of the porcine endogenous retrovirus gag polyprotein, blocks retrovirus production, providing the possibility of eliminating the risk of infection in xenotranspl ... | 2003 | 14581550 |
relative age of proviral porcine endogenous retrovirus sequences in sus scrofa based on the molecular clock hypothesis. | porcine endogenous retroviruses (perv) are discussed as putative infectious agents in xenotransplantation. perv classes a, b, and c harbor different envelope proteins. two different types of long terminal repeat (ltr) structures exist, of which both are present only in perv-a. one type of ltr contains a distinct repeat structure in u3, while the other is repeatless, conferring a lower level of transcriptional activity. since the different ltr structures are distributed unequally among the provir ... | 2003 | 14581574 |
some morphological, growth, and genomic properties of human cells chronically infected with porcine endogenous retrovirus (perv). | a major concern in using porcine organs for transplantation is the potential of transmission of porcine endogenous retrovirus (perv). to investigate the long-term effects of perv infection on human cells, human embryonic kidney cell line hek-293 infected with perv pk-15 was maintained for up to 72 passages and samples were harvested at intervals for use in morphological, growth, and genomic analyses. morphology, dna content/cell, and doubling time of uninfected and infected cells were similar. r ... | 2003 | 14608403 |
genotyping of porcine endogenous retroviruses from a family of miniature swine. | the identification of animals in an inbred miniature swine herd that consistently fail to produce replication- competent humantropic porcine endogenous retrovirus (perv) has prompted studies on the biology of perv in transmitter and nontransmitter animals. we analyzed perv rna transcript profiles in a family of inbred miniature swine (sla(d/d) haplotype) in which individual members differed in their capacity to generate humantropic and ecotropic (i.e., pigtropic) virus. we identified unique haei ... | 2004 | 14671113 |
hybrid bioartificial liver: establishing a reversibly immortalized human hepatocyte line and developing a bioartificial liver for practical use. | recently, much attention has been attracted by a novel therapy for liver failure using a hybrid bioartificial liver (bal) support device that incorporates living liver cells. researchers in various fields have considered the following cells for potential use in bals: human embryonic stem (es) cells; somatic stem cells; differentiated tissue cells; and cells derived from tissues of different animal species, particularly from the pig. with their pluripotency, human es cells are extremely useful, a ... | 2003 | 14691665 |
sensitivity to human serum of gammaretroviruses produced from pig endothelial cells transduced with glycosyltransferase genes. | reduction of pig cell-surface alpha-galactosyl (gal) epitope, galalpha1, 3galbeta1, 4glcnac-r, by the introduction of glycosyltransferase genes is effective in suppressing hyperacute rejection (har) in pig-to-human xenotransplantation. the transmission of porcine endogenous retroviruses (pervs) has been recognized as a potential risk factor associated with xenotransplantation. in this study, effects of the introduction of glycosyltransferase genes to pig cells on the sensitivity of gammaretrovir ... | 2003 | 14708522 |
[the quantity analysis of reverse transcriptase in porcine endogenous retrovirus expressed in banna minipig inbred]. | quantitative rt(reverse transcriptase) assay was established to detect the reverse transcriptase in plasma of thirty-four chinese banna minipig inbred in this work. the protocol was given in the rt kit (roche), using hiv-1 as the positive control of the kit and supernatant of pk-15 as the perv positive control respectively. the results show that positive reverse transcriptase reaction can be detected in the plasma of the pigs, but the levels are much lower than that of hiv-1 and lower than that ... | 2003 | 14716853 |
limited infection without evidence of replication by porcine endogenous retrovirus in guinea pigs. | porcine endogenous retrovirus (perv) may potentially be transmitted through porcine xenotransplantation products administered to humans. this study examined the feasibility of using guinea pigs as a model to characterize the in vivo infectivity of perv. to enhance the susceptibility of guinea pigs to retroviral infection or genomic integration, moderate physiological or immunological changes were induced prior to exposing the animals to perv. quantitative perv-specific pcr performed on all teste ... | 2004 | 14718614 |