Retroviral Restriction Factors and Infectious Risk in Xenotransplantation: Retroviral Restriction in Xenotransplantation (original) (raw)
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Porcine endogenous retrovirus and other viruses in xenotransplantation
Current Opinion in Organ Transplantation, 2009
Purpose of review Potential transmission of zoonotic porcine viruses is a major safety issue in xenotransplantation. This review will first summarize recent studies involving transmission and control of the major concern, porcine endogenous retrovirus (PERV). Second, the potential for zoonotic transfer and safety measures required against other viruses of concern will be discussed. Recent findings As studies on PERV genomics continue, distribution of PERV, particularly porcine endogenous retrovirus-C in individual pigs in relation to their ability to transmit PERV in vitro, is becoming clearer. However, further study is required to establish pig lines devoid of problematic copies of PERV. As an extra level of safety, several strategies have been sought, with some success, to reduce PERV infectivity and be used to produce transgenic, PERV-suppressed pigs. Porcine herpesviruses, hepatitis E virus, arenaviruses and an Anellovirus, Torque teno virus, have been highlighted as other viruses of potential risk. Summary Xenotransplantation is a unique situation in which pathogen monitoring may be required to be more comprehensive than that required for specific pathogen-free sources. With evidence of transmission of novel viruses via allotransplantation, significant attention should be paid to emerging and as yet unknown viruses.
Endogenous Retroviruses: A Potential Problem for Xenotransplantation? a
Annals of the New York Academy of Sciences, 1998
To overcome the shortage of suitable human donors for transplantation attention has recently turned to the possibility of using genetically modified pigs as a source of cells and organs. It has been suggested that such procedures might facilitate the introduction of novel retroviruses, normally resident in the pig germ line, into the human population (Stoye and Coffin, Nature Medicine 1: 1100, l995). The consequences of such a transfer remain unclear; however, the demonstration that certain porcine cell lines express infectious retroviruses which can infect human cells (Patience et al., Nature Medicine 3: 282-286, 1997) emphasizes that there are grounds for practical concern. We have now cloned the envelope genes of the expressed viruses and are using these clones in studies of the interaction of the porcine viruses with their cellular receptors. We have also initiated studies of the inheritance and expression of human-tropic endogenous proviruses present in different pig populations. These studies reveal that at least two classes of human-tropic endogenous porcine retrovirus are widely distributed in pigs (Le Tissier et al., Nature 389: 681-681, 1997). The implications of our results for assessing the potential risks of retroviral transfer during xenotransplantation are discussed.
Transplant International, 2001
The question whether porcine xenografts can lead to porcine endogenous retrovirus (PERV) infection of recipients is critical for the evaluation of the safety of pigto-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-supporting pig-to-primate kidney xenotransplantation model: porcine kidneys were transplanted, whereas the functioning recipient kidneys remained in situ. Subsequent to rejection (after 2 hours to 15 days), xenografts were removed, and recipients remained alive for up to 287 days. Immunosuppressive therapy based on cyclophosphamide, cyclosporine, and steroids was maintained for 28 days after transplantation. Using appropriate PCR assays, xenochimerism was found in tissue samples and partly even in peripheral blood leukocytes (PBLs) while the porcine kidneys were in situ. After graft removal, xenochimerism was no longer detectable, thus allowing analysis for possible PERV transmission.
Pig endogenous retroviruses and xenotransplantation
Xenotransplantation, 2002
Xenotransplantation of porcine organs might provide an unlimited source of donor organs to treat endstage organ failure diseases in humans. However, pigs harbour retroviruses with unknown pathogenic potential as an integral part of their genome. While until recently the risk of interspecies transmission of these porcine endogenous retroviruses (PERV) during xenotransplantation has been thought to be negligible, several reports on infection of human cells in vitro and spread of PERV from transplanted porcine islets in murine model systems have somewhat challenged this view. Here, we compile available data on PERV biology and diagnostics, and discuss the significance of the results with regard to the safety of clinical xenotransplantation.
Current Microbiology, 2013
The pig appears to be the most promising animal donor of organs for use in human recipients. Among several types of pathogens found in pigs, one of the greatest problems is presented by porcine endogenous retroviruses (PERVs). Screening of the source pig herd for PERVs should include analysis of both PERV DNA and RNA. Therefore, the present study focuses on quantitative analysis of PERVs in different organs such as the skin, heart, muscle, and liver and blood of transgenic pigs generated for xenotransplantation. Transgenic pigs were developed to express the human a-galactosidase, the human a-1,2-fucosyltransferase gene, or both genetic modifications of the genome (Lipinski et al., Medycyna Wet 66:316-322, 2010; Lipinski et al., Ann Anim Sci 12:349-356, 2012; Wieczorek et al., Medycyna Wet 67:462-466, 2011). The copy numbers of PERV DNA and RNA were evaluated using real-time Q-PCR and QRT-PCR, respectively. Comparative analysis of all PERV subtypes revealed the following relationships: PERV A [ PERV B [ PERV C. PERV A and B
Viruses, 2019
Pigs are used as potential donor animals for xenotransplantation. However, porcine endogenous retrovirus (PERV), shown to infect both human and non-human primate (NHP) cells in vitro, presents a risk of transmission to humans in xenotransplantation. In this study, we analyzed PERV transmission in various organs after pig-to-NHP xenotransplantation. We utilized pig-to-NHP xenotransplant tissue samples obtained using two types of transgenic pigs from the National Institute of Animal Science (NIAS, Republic of Korea), and examined them for the existence of PERV genes in different organs via PCR and RT-PCR with specific primers. To determine PERV insertion into chromosomes, inverse PCR using PERV long terminal repeat (LTR) region-specific primers was conducted. The PERV gene was not detected in NHP organs in cardiac xenotransplantation but detected in NHP bladders in renal xenotransplantation. The insertion experiment confirmed that PERVs originate from porcine donor cells rather than i...