Absence of infection in pigs inoculated with high-titre recombinant PERV-A/C

Kaulitz, Danny; Mihica, Debora; Plesker, Roland; Geissler, Anne; Tönjes, Ralf R.; Denner, Joachim

doi:10.1007/s00705-010-0896-5

Cited by 11 publications

(12 citation statements)

References 32 publications

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“…They are characterised by a higher replication rate [64,65]. Despite this, first attempts to infect pigs with a PERV-A/C recombinant failed, certainly due to the innate immune system [66]. …”

Section: Evidence For Recombination and De Novo Integration In Vivomentioning

confidence: 99%

How Active Are Porcine Endogenous Retroviruses (PERVs)?

Denner

2016

Viruses

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Porcine endogenous retroviruses (PERVs) represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs), which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (CRISPR/Cas) technology.

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Section: Evidence For Recombination and De Novo Integration In Vivomentioning

confidence: 99%

How Active Are Porcine Endogenous Retroviruses (PERVs)?

Denner

2016

Viruses

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“…Although PERV-A/C were shown to replicate and integrate de novo in healthy (14,236,342,347) and diseased (89) pigs, a first attempt to infect PERV-C-negative pigs in vivo with a cell-free high-titer PERV-A/C failed (158). Neither provirus integration in different organs nor antibody production was observed in the inoculated animal.…”

Section: Pervsmentioning

confidence: 99%

“…Virus protein expression was studied using specific antisera in an immunoperoxidase assay (IPA) (302), an immunofluorescence assay (61,107,163), and a Western blot assay (158,202,312) and by immunohistochemistry (Bittmann et al, unpublished data) (Fig. 4).…”

Section: Pervsmentioning

confidence: 99%

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

2012

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SUMMARY Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference.

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“…Artificial inoculation of pigs with PERV A/C recombinants did not cause inte gration of proviruses into the DNA with the formation of proper antibodies. This indicates that the retrovirus is not easily transmissible between animals (Kaulitz et al, 2011b).…”

Section: Rna Expression and Release Of Pervmentioning

confidence: 99%

Porcine endogenous retroviruses: What are the risks of infection transmission in xenotransplantation?

Yudin

Aitnazarov

Ermolaev

2011

Russ J Genet Appl Res

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Modern studies on porcine endogenous retroviruses are considered in the review. Data on the nucleotide sequences of retroviruses, their expression, and the isolation of mature virions is discussed. The tropism of endogenous retroviruses to human cells and retrospective studies of patients are considered in detail. A critical overview of works on in vitro and in vivo interspecific transmission of porcine endogenous retroviruses is presented. Tactics for preventing possible infection and treating humans for it are discussed. Based on the overviewed data, it is concluded that the risk of infection transmission from xenograft recipients to the rest of the population is very low. This low risk can be further reduced by careful observation and, prob ably, vaccination of contacting persons, as well as by preventive use of antiviral drugs. The minor risk of infec tion transmission can also be reduced by application of modern biotechnological methods to raise pigs that have no endogenous viruses tropic to humans.

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Absence of infection in pigs inoculated with high-titre recombinant PERV-A/C

Cited by 11 publications

References 32 publications

How Active Are Porcine Endogenous Retroviruses (PERVs)?

How Active Are Porcine Endogenous Retroviruses (PERVs)?

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

Porcine endogenous retroviruses: What are the risks of infection transmission in xenotransplantation?

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