APOBEC3 Proteins and Porcine Endogenous Retroviruses

Dörrschuck, E.; Münk, Carsten; Tönjes, Ralf R.

doi:10.1016/j.transproceed.2008.03.032

Cited by 18 publications

(17 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was found that PERV was significantly inhibited by various porcine A3s in single-round as well as spreading virus assays. PERV inhibition strongly correlated with a specific cytidine deamination in viral genomes for the trinucleotides 5=TGC (edited nucleotide is underlined), for poA3Z2 as well as poA3Z2-Z3, and 5=CAC, for A3Z3 (93,94,179). These results strongly implicate that human and porcine A3s can inhibit PERV replication in vivo, thereby reducing the risk of potential infection of human cells by PERV in the course of pig-to-human xenotransplantation.…”

Section: Pervsmentioning

confidence: 69%

“…Furthermore, it was reported that overexpressed poA3Z2-Z3 did not significantly interfere with PERV transmission, and it was concluded that PERV was resistant to its species-specific A3 protein (150). Subsequently, the chromosomal porcine A3 locus for poA3Z2 and poA3Z3 was reanalyzed (93,94). Data showed that pigs express four different A3 mRNAs, encoding poA3Z2 and poA3Z3 and, by readthrough transcription and alternative splicing, poA3Z2-Z3 and poA3Z2-Z3 splice variant A (SVA).…”

Section: Pervsmentioning

confidence: 99%

See 1 more Smart Citation

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

2012

View full text Add to dashboard Cite

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.

show abstract

Section: Pervsmentioning

confidence: 69%

Section: Pervsmentioning

confidence: 99%

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

2012

View full text Add to dashboard Cite

show abstract

“…It was found that PERV was significantly inhibited by various porcine A3s in single-round as well as in spreading virus assays. PERV inhibition strongly correlated with a specific cytidine deamination in viral genomes in the trinucleotide 5’TGC for poA3Z2 as well as poA3Z2-Z3 and 5’CAC for A3Z3 [54,55,56]. These results strongly suggest that human and porcine A3s could inhibit PERV replication in vivo, thereby reducing the risk of potential infection of human cells by PERV in the course of pig-to-human xenotransplantation.…”

Section: Perv Activity and Cellular Restriction Factorsmentioning

confidence: 86%

“…Subsequently, the chromosomal porcine A3 locus for poA3Z2 and poA3Z3 was re-analysed [54,55]. The two A3 genes in pigs encode at least four different mRNAs: A3Z2, A3Z3, A3Z2-Z3, and A3Z2-Z3 splice variant A (SVA).…”

Section: Perv Activity and Cellular Restriction Factorsmentioning

confidence: 99%

How Active Are Porcine Endogenous Retroviruses (PERVs)?

Denner

2016

Viruses

View full text Add to dashboard Cite

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.

show abstract

“…Two groups have adopted this strategy and produced transgenic pigs expressing small interfering RNAs for the inhibition of PERV expression (5,6,22). Other molecules have been investigated and could potentially be employed in the development of transgenic pigs: intracellularly expressed single domain antibodies directed against PERV Gag (3), sugar-modifying enzymes to remodel PERV envelope glycoprotein (19), and the restriction factor human APOBEC3G (7,13).…”

mentioning

confidence: 99%

Regulation of Porcine Endogenous Retrovirus Release by Porcine and Human Tetherins

Mattiuzzo

Ivol

Takeuchi

2010

J Virol

View full text Add to dashboard Cite

The risk of transmission of porcine endogenous retrovirus (PERV) is one of the major safety issues in xenotransplantation. Human tetherin, recently described as an antiviral protein able to inhibit the release of enveloped viruses, and its porcine homologue were shown to inhibit PERV release from producer cells, establishing themselves as candidate molecules to suppress PERV production in porcine xenografts by animal engineering.

show abstract

APOBEC3 Proteins and Porcine Endogenous Retroviruses

Cited by 18 publications

References 44 publications

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

How Active Are Porcine Endogenous Retroviruses (PERVs)?

Regulation of Porcine Endogenous Retrovirus Release by Porcine and Human Tetherins

Contact Info

Product

Resources

About