| no expression of porcine endogenous retrovirus after pig to monkey xenotransplantation. | this study was performed to investigate the expression of two porcine endogenous retrovirus (perv) elements, perv gag and full-length conserved perv, in blood cells collected periodically from organ-recipient monkeys that underwent pig to non-human primate xenotransplantation. the heart and kidney-respectively acquired from α-1,3-galactosyltransferase knockout (gt-ko) pigs that survived for24 and 25 days-were xenografted into cynomolgus monkeys. the two perv elements expressed in the xenografted ... | 2014 | 24999364 |
| inhibition of budding/release of porcine endogenous retrovirus. | perv is integrated into the genome of all pigs. perv-a and perv-b are polytropic and can productively infect human cell lines, whereas perv-c is ecotropic. recombinant perv-a/c can infect human cells and exhibits high titer replication. therefore, use of pigs for human xenotransplantation raises concerns about the risks of transfer of this infectious agent from donors to xenotransplantation recipients. to establish strategies to inhibit perv production from cells, in the present study, we invest ... | 2014 | 24931347 |
| lack of antibody response in pigs immunized with the transmembrane envelope protein of porcine endogenous retroviruses. | recently, we immunized different mammalian species (goats, mice, rats, rabbits, guinea pigs and hamsters) with the recombinant ectodomain of the transmembrane envelope (tm) protein p15e of porcine endogenous retrovirus (perv). in all cases, neutralizing immune sera were induced, which recognized epitopes in the fusion peptide proximal region and the membrane proximal external region of p15e. in order to analyse whether pigs are also able to produce such antibodies, and whether such antibodies ca ... | 2014 | 24828332 |
| microbiological safety of the first clinical pig islet xenotransplantation trial in new zealand. | xenotransplantation using pig cells, tissues, or organs may be associated with the transmission of porcine microorganisms and the development of zoonoses. among all porcine microorganisms porcine endogenous retroviruses (pervs) represent a special risk because they are integrated in the genome of all pigs and able to infect human cells. in previous preclinical and retrospective clinical trials of xenotransplantation, no transmission of perv was observed. the first clinical trial of (alginate-enc ... | 2014 | 24801820 |
| tetherins of various species inhibit the release of porcine endogenous retrovirus from human cells. | pigs are considered as suitable xenotransplantation organ donors. however, the risk of pathogen transmission from pigs to human is a major concern in the transplantation of porcine tissues since it had been shown that porcine endogenous retroviruses (pervs) can infect human cells. tetherin has recently been described as a host restriction factor that blocks the release of virus particles from cells infected with some enveloped viruses. we compared tetherins derived from various species in their ... | 2014 | 24717029 |
| detection of porcine endogenous retrovirus in xenotransplantation. | xenotransplantation can provide a virtually limitless supply of cells, tissues and organs for a variety of therapeutic procedures. cells and tissues for use in human transplantation procedures could be supplied using material taken from pigs. however, there is a potential risk of transmission of porcine infectious agents, including porcine endogenous retroviruses (pervs), to a novel human host, with as yet unknown consequences. three subtypes of perv have been identified, of which both perv-a an ... | 2014 | 24607257 |
| porcine endogenous retrovirus (perv) infection of hek-293 cell line alters expression of human endogenous retrovirus (herv-w) sequences. | the risk of infections of human recipients after xenotransplantations is now mainly represented by porcine endogenous retroviruses (pervs) as these particles are part of the porcine genome. as in all vertebrates, human genome harbours its own numerous genetic sequences of retroviral origin; it is estimated that they comprise about 8 % of the human genome. because some of them play an important role in human physiology, it is valuable to estimate whether the presence of pervs in human cells influ ... | 2014 | 24594055 |
| comparison of the effects of retroviral restriction factors involved in resistance to porcine endogenous retrovirus. | three major classes of retroviral restriction factors (apobec3g, tetherin, and trim5α) have been identified in mammals. restriction factors are cellular proteins that are able to limit viral replication by targeting specific steps of the viral life cycle. to evaluate which restriction factor is the most effective to inhibit the replication of porcine endogenous retroviruses (pervs), the antiviral activity of each restriction factor was compared. in pseudotype assay, the antiviral activity of hum ... | 2014 | 24448163 |
| comparison of porcine endogenous retroviruses infectious potential in supernatants of producer cells and in cocultures. | porcine endogenous retroviruses (perv) pose a zoonotic risk potential in pig-to-human xenotransplantation given that perv capacity to infect different human cell lines in vitro has been clearly shown in the past. however, perv infectious potential for human peripheral blood mononuclear cells (hupbmc) has been also demonstrated, albeit with controversial results. as productive perv infection of hupbmc involves immune suppression that may attract opportunistic pathogens as shown for other retrovir ... | 2014 | 24447212 |
| ghb receptor targets in the cns: focus on high-affinity binding sites. | γ-hydroxybutyric acid (ghb) is an endogenous compound in the mammalian brain with both low- and high-affinity receptor targets. ghb is used clinically in the treatment of symptoms of narcolepsy and alcoholism, but also illicitly abused as the recreational drug fantasy. major pharmacological effects of exogenous ghb are mediated by gaba subtype b (gabab) receptors that bind ghb with low affinity. the existence of ghb high-affinity binding sites has been known for more than three decades, but the ... | 2014 | 24269284 |
| porcine endogenous retrovirus infection changes the expression of inflammation-related genes in lipopolysaccharide-stimulated human dermal fibroblasts. | the present study focuses on explaining the interaction between porcine endogenous retroviruses (pervs) and human cells in inflammatory conditions. the differences in expression of selected inflammation-related genes in human dermal fibroblasts (nhdf) infected with pervs with and without lipopolysaccharide stimulation were identified. | 2013 | 24157628 |
| inhibition of porcine endogenous retrovirus in pk15 cell line by efficient multitargeting rna interference. | to effectively suppress porcine endogenous retroviruses (perv)s, rnai technique was utilized. rnai is the up-to-date skill for gene knockdown which simultaneously multitargets both gag and pol genes critical for replication of pervs. previously, two of the most effective sirnas (gag2, pol2) were found to reduce the expression of pervs. concurrent treatment of these two sirnas (gag2+pol2) showed knockdown efficiency of up to 88% compared to negative control. however, despite the high initial knoc ... | 2014 | 24138389 |
| long-term igg response to porcine neu5gc antigens without transmission of perv in burn patients treated with porcine skin xenografts. | acellular materials of xenogenic origin are used worldwide as xenografts, and phase i trials of viable pig pancreatic islets are currently being performed. however, limited information is available on transmission of porcine endogenous retrovirus (perv) after xenotransplantation and on the long-term immune response of recipients to xenoantigens. we analyzed the blood of burn patients who had received living pig-skin dressings for up to 8 wk for the presence of perv as well as for the level and n ... | 2013 | 23945141 |
| susceptibility of human liver cells to porcine endogenous retrovirus. | the risk of porcine endogenous retrovirus infection is a major barrier for pig-to-human xenotransplant. porcine endogenous retrovirus, present in porcine cells, can infect many human and nonhuman primate cells in vitro, but there is no evidence available about in vitro infection of human liver cells. we investigated the susceptibility of different human liver cells to porcine endogenous retrovirus. | 2013 | 23901808 |
| construction and characterization of an infectious replication competent clone of porcine endogenous retrovirus from chinese miniature pigs. | xenotransplantation from animals has been considered to be a preferable approach to alleviate the shortage of human allografts. pigs are the most suitable candidate because of the anatomical and physiological similarities shared with humans as well as ethical concerns. however, it may be associated with the risk of transmission of infectious porcine pathogens. porcine endogenous retroviruses (pervs) are of particular concern because they have been shown to infect human cells in vitro. to date, r ... | 2013 | 23837947 |
| promoter activity analysis and methylation characterization of ltr elements of pervs in nih miniature pig. | the potential risk of porcine endogenous retrovirus (perv) transmission is an important issue in xenotransplantation (pig-to-human transplantation). long terminal repeats (ltrs) in perv elements show promoter activity that could affect neighboring functional genes. the methylation status and promoter activities of 3 ltr structures (perv-ltr1, ltr2, and ltr3 elements) belonging to the perv-a family were examined using luciferase reporter genes in human liver cell lines (hepg2 and hep3b). the perv ... | 2013 | 23832305 |
| novel neutralising antibodies targeting the n-terminal helical region of the transmembrane envelope protein p15e of the porcine endogenous retrovirus (perv). | previously, immunising different species with the transmembrane envelope protein p15e of the porcine endogenous retrovirus (perv), neutralising antibodies were induced which recognised epitopes in the fusion peptide proximal region (fppr) and in the membrane-proximal external region (mper). only the mper-specific antibodies were shown to neutralise and these antibodies targeted epitopes in the mper similarly localised as the epitopes recognised by antibodies broadly neutralising hiv-1 such as 2f ... | 2014 | 23729215 |
| ethical and regulatory guidelines in clinical trials of xenocorneal transplantation in korea; the korean xenocorneal transplantation consensus statement. | to establish the consensus about the conditions for undertaking clinical trials in xenocorneal transplantation in korea, specific issues regarding the xenocorneal transplantation on ethical and regulatory aspects are addressed, and the guidelines to conduct clinical trial of the xenocorneal transplantation are proposed. | 2013 | 23683073 |
| knockdown of porcine endogenous retroviruses by rna interference in chinese experimental miniature pig fibroblasts. | the clinical application of porcine-derived xenotransplants is limited by the potential risk of infection due to the presence of porcine endogenous retrovirus (perv) in tissues, organs, and cells. the establishment of pig fibroblasts with low perv expression and without perv-c can provide a nuclear donor to generate a safer transgenic pig. | 2013 | 23498816 |
| preparation of immunogen-reduced and biocompatible extracellular matrices from porcine liver. | decellularized biologic matrices are plausible biomedical materials for the bioengineering in liver transplantation. however, one of the concerns for safe medical application is the lack of objective assessment of the immunogen within the materials and the in vivo immune responses to the matrices. the purpose of this study was the production of immunogen-reduced and biocompatible matrices from porcine liver. in the present study, 0.1% sds solution was effective for removing dna fragments and seq ... | 2013 | 23068617 |
| evaluation of a novel hybrid bioartificial liver based on a multi-layer flat-plate bioreactor. | to evaluate the efficacy and safety of a hybrid bioartificial liver (hbal) system in the treatment of acute liver failure. | 2012 | 22851870 |
| binding of transcription factor activating protein 2 γ on the 5'-proximal promoter region of human porcine endogenous retrovirus subgroup a receptor 2/gpr172b. | xenotransplantation is one of the solutions for the shortage of organ donors, and pigs have been considered to be the most suitable animal donors. specific pathogen-free pigs are utilized in the xenotransplantation; however, pigs have infectious gammaretroviruses, named porcine endogenous retroviruses (pervs) in their genome. of them, perv-a and perv-b can infect human cells in vitro and potentially induce diseases like other gammaretroviruses. the human cellular receptors for perv-a were identi ... | 2012 | 22702469 |
| detailed mapping of determinants within the porcine endogenous retrovirus envelope surface unit identifies critical residues for human cell infection within the proline-rich region. | replication-competent porcine endogenous retroviruses (pervs) are either human cell tropic (perv-a and perv-b) or non-human cell tropic (perv-c). we previously demonstrated that perv in vitro cell tropism is modulated by 2 residues within the c terminus of su and that the perv receptor binding domain (rbd) extends beyond the variable regions a and b (vra and vrb, respectively), to include the proline rich-region (prr) of su (m. gemeniano et al., virology 346:108-117, 2000; t. argaw et al., j. vi ... | 2012 | 22696659 |
| potential zoonotic infection of porcine endogenous retrovirus in xenotransplantation. | porcine endogenous retrovirus (perv) is considered the major biosafety issue in xenotransplantation. several techniques have been employed for the analysis of the perv status in the animal donor and for the assessment of perv transmission/infection in the xenograft recipient. in this chapter, methods to assess the expression of perv and the potential for perv transmission from a donor animal are described in addition to the identification of relevant loci within the porcine genome.perv detection ... | 2012 | 22566002 |
| [new evidence of porcine endogenous retrovirus transmission with new bio-artificial liver system: a experimental study]. | to investigate the potential transmissibility of porcine endogenous retrovirus (perv) from a newly-developed porcine hepatocyte bioartificial liver (bal) system prior to human clinical trial by using a live canine model. | 2012 | 22464706 |
| porcine endogenous retrovirus copy number in different pig breeds is not related to genetic diversity. | the risk of zoonoses is a major obstacle to xenotransplantation. porcine endogenous retrovirus (perv) poses a potential risk of zoonotic infection, and its control is a prerequisite for the development of clinical xenotransplantation. the copy number of perv varies among different breeds, and it has been suggested that the perv integrations number is increased by inbreeding. the purpose of this study was (i) to examine the copy number of perv in different spanish pig breeds, spanish wild boar an ... | 2012 | 22348392 |
| degradation effect of diepoxide fixation on porcine endogenous retrovirus dna in heart valves: molecular aspects. | xenotransplantations of porcine cells, tissues, and organs involve a risk of zoonotic viral infections in recipients, including by porcine endogenous retroviruses (pervs), which are embedded the genome of all pigs. an appropriate preparation of porcine heart valves for transplantation can prevent retroviral infection. therefore, the present study focuses on the effect of epoxy compounds and glutaraldehyde on the perv presence in porcine heart valves prepared for clinical use. | 2012 | 22307333 |
| the sequence and analysis of a chinese pig genome. | the pig is an economically important food source, amounting to approximately 40% of all meat consumed worldwide. pigs also serve as an important model organism because of their similarity to humans at the anatomical, physiological and genetic level, making them very useful for studying a variety of human diseases. a pig strain of particular interest is the miniature pig, specifically the wuzhishan pig (wzsp), as it has been extensively inbred. its high level of homozygosity offers increased ease ... | 2012 | 23587058 |
| polymerase chain reaction in detection of porcine endogenous retrovirus (perv) from porcine tissues. | pigs offer an unlimited source of xenografts for humans. the use of transplants from animal origin offers a potential solution to the limited supply of human organs and tissues. however, like many other mammalian species, pigs harbor porcine endogenous retrovirus (perv), which are encoded in their genomic dna and are assumed to have been integrated into the porcine germline. the ability of perv to infect human cells in vitro has heightened safety concerns regarding the transmission of perv to pi ... | 2009 | 23100752 |
| porcine endogenous retrovirus-a/c: biochemical properties of its integrase and susceptibility to raltegravir. | porcine endogenous retroviruses (pervs) are present in the genomes of pig cells. the perv-a/c recombinant virus can infect human cells and is a major risk of zoonotic disease in the case of xenotransplantation of pig organs to humans. raltegravir (ral) is a viral integrase (in) inhibitor used in highly active antiretroviral treatment. in the present study, we explored the potential use of ral against perv-a/c. we report (i) a three-dimensional model of the perv-a/c intasome complexed with ral, ( ... | 2015 | 26296914 |
| characterization of molecular clones of porcine endogenous retrovirus-a containing different numbers of u3 repeat boxes in the long terminal repeat region. | when full-length molecular clones of porcine endogenous retrovirus (perv)-a and porcine endogenous retrovirus (perv)-b were passaged on human cells, an increase in the length of the long terminal repeat (ltr) was reported. a 39-bp repeat box in the ltr u3 region was multimerized dynamically upon replication, acting as a viral enhancer element that contains binding sites for nuclear transcription factor nf-y. to analyze the optimum number of 39-bp repeats for viral replication, molecular clones o ... | 2012 | 22343070 |
| improved pig donor screening including newly identified variants of porcine endogenous retrovirus-c (perv-c). | porcine endogenous retroviruses (perv) are widely distributed in the genomes of pigs. perv-a and perv-b are present in all pigs. they infect human cells in vitro and therefore represent a risk for xenotransplantation when pig cells, tissues or organs are used. perv-c infects only pig cells and is not present in the genomes of all pigs. however, perv-a/c recombinants infecting human cells and characterized by high replication titers were found in pigs. to select perv-c-free animals that cannot ge ... | 2013 | 23053520 |
| long-term safety from transmission of porcine endogenous retrovirus after pig-to-non-human primate corneal transplantation. | the risk of xenozoonosis mainly by porcine endogenous retrovirus (perv) has been considered as one of the main hurdles in xenotransplantation and therefore should be elucidated prior to the clinical use of porcine corneal grafts. accordingly, an investigation was performed to analyze the infectivity of pervs from porcine keratocytes to human cells, and the long-term risk of transmission of pervs was determined using pig-to-non-human primate (nhp) corneal transplantation models. | 2017 | 28503733 |
| can antiretroviral drugs be used to treat porcine endogenous retrovirus (perv) infection after xenotransplantation? | porcine endogenous retroviruses (pervs) are integrated in the genome of all pigs; they are released as infectious particles, and under certain conditions they can infect human cells. therefore, they represent a risk when pigs are used as sources of cells, tissues, or organs for xenotransplantation. xenotransplantation is under development due to the increasing shortage of human transplants. whereas most porcine microorganisms which may be able to induce a disease (zoonosis) in the transplant rec ... | 2017 | 28786944 |
| an69 hollow fiber membrane will reduce but not abolish the risk of transmission of porcine endogenous retroviruses. | as the risk of porcine endogenous retrovirus (perv) infection is a major obstacle to the xenotransplantation of porcine tissue, we investigated whether an an69 hollow fibre membrane, used for islets of langerhans transplantation, could prevent the transfer of pervs and thus reduce the risk of perv infection. pk15 cells were used as a perv source. a specific and highly sensitive rcr was used for detection of a perv provirus dna (gag region) and a porcine mtdna. human u293 cells were incubated in ... | 2005 | 28849982 |
| inactivation of porcine endogenous retrovirus in pigs using crispr-cas9. | xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. in addition to the concern on pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (pervs) has impeded the clinical application of this approach. earlier, we demonstrated the feasibility of inactivating perv activity in an immortalized pig cell line. here, we confirmed that pervs infect human cells, and observed the horizontal t ... | 2017 | 28798043 |
| characterization of porcine endogenous retrovirus expression in neonatal and adult pig pancreatic islets. | pig islets represent an alternative to the current modes of treatment for patients with diabetes. however, the concerns over pathogen transmission including that of perv limit their immediate, widespread usage in humans. it has been previously demonstrated that perv copy number and particularly expression levels can vary considerably between individuals and within different tissues of a single animal. in general, expression levels have been found to be particularly low in the pancreas compared t ... | 2017 | 28444910 |
| three cysteine residues of slc52a1, a receptor for the porcine endogenous retrovirus-a (perv-a), play a critical role in cell surface expression and infectivity. | porcine endogenous retrovirus-a (perv-a), a gammaretrovirus, infects human cells in vitro, thus raising the potential risk of cross-species transmission in xenotransplantation. two members of the solute carrier family 52 (slc52a1 and slc52a2) are perv-a receptors. site-directed mutagenesis of the cdna encoding slc52a1 identified that only one of two putative glycosylation signals is occupied by glycans. in addition, we showed that glycosylation of slc52a1 is not necessary for perv-a receptor fun ... | 2017 | 28437635 |
| the resurgence of xenotransplantation. | there has been an upsurge of interest in xenotransplantation in recent years. this resurgence can attributed to a combination of factors. first, there has been a dramatic improvement in efficacy in several preclinical models, with maximum xenograft survival times increasing to 950 days for islets, 945 days for hearts, and 310 days for kidneys. second, the rapid development of genome editing technology (particularly the advent of clustered regularly interspaced short palindromic repeats/cas9) has ... | 2017 | 28397351 |
| immunological response in cynomolgus macaques to porcine α-1,3 galactosyltransferase knockout viable skin xenotransplants-a pre-clinical study. | allogeneic skin recovered from human deceased donors (hdd) has been a mainstay interim treatment for severe burns, but unfortunately risk of infectious disease and availability limitations exist. genetically engineered ɑ-1,3 galactosyltransferase knockout (galt-ko) porcine source animals for viable skin xenotransplants may provide a promising clinical alternative. | 2020 | 32781479 |
| novel spheroid reservoir bioartificial liver improves survival of nonhuman primates in a toxin-induced model of acute liver failure. | this study aims to evaluate the effectiveness and safety of the spheroid reservoir bioartificial liver (srbal) with porcine hepatocyte organoids in a preclinical nonhuman primate model of acute liver failure (alf). methods: thirty healthy rhesus monkeys were infused with α-amanitin and lipopolysaccharide and randomized into five groups (alf alone control group; sham no-cell srbal treatment group; groups a, b and c with srbal treatment started at 12 h, 24 h and 36 h after induction of alf, respec ... | 2018 | 30555564 |