Abstract

In the context of the shortage of organs and other tissues for use in human transplantation, xenotransplantation procedures with material taken from pigs have come under increased consideration. However, there are unclear consequences of the potential transmission of porcine pathogens to humans. Of particular concern are porcine endogenous retroviruses (PERVs). Three subtypes of PERV have been identified, of which PERV-A and PERV-B have the ability to infect human cells in vitro. The PERV-C subtype does not show this ability but recombinant PERV-A/C forms have demonstrated infectivity in human cells. In view of the risk presented by these observations, the International Xenotransplantation Association recently indicated the existence of four strategies to prevent transmission of PERVs. This article focuses on the molecular aspects of PERV infection in xenotransplantation and reviews the techniques available for the detection of PERV DNA, RNA, reverse transcriptase activity and proteins, and anti-PERV antibodies to enable carrying out these recommendations. These methods could be used to evaluate the risk of PERV transmission in human recipients, enhance the effectiveness and reliability of monitoring procedures, and stimulate discussion on the development of improved, more sensitive methods for the detection of PERVs in the future.

Highlights

  • According to the United States Public Health Service, xenotransplantation includes any procedure that involves the transplantation, implantation, or infusion into a human recipient of live cells, tissues, or organs from a nonhuman animal source or human body fluids, cells, tissues, or organs that have had ex vivo contact with live nonhuman animal cells, tissues, or organs [1]

  • Porcine endogenous retroviruses (PERVs) represent one of several types of viruses found in pigs that might be transmitted to humans through xenotransplantation [2,3,4,5,6,7]

  • Detection of the PERV provirus genome can be achieved by the use of polymerase chain reaction (PCR), using primers that are complementary to a variety of PERV DNA sequences

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Summary

Introduction

According to the United States Public Health Service, xenotransplantation includes any procedure that involves the transplantation, implantation, or infusion into a human recipient of live cells, tissues, or organs from a nonhuman animal source or human body fluids, cells, tissues, or organs that have had ex vivo contact with live nonhuman animal cells, tissues, or organs [1]. The pig has been considered a potential source animal for xenotransplantation materials because of the comparable sizes of human and porcine organs, the similar physiological parameters of the two species, the ease of breeding pigs and the significant phylogenetic distance between pigs and humans, which reduces the risk of transmission of viral infections. Porcine endogenous retroviruses (PERVs) represent one of several types of viruses found in pigs that might be transmitted to humans through xenotransplantation [2,3,4,5,6,7]

Xenotransplantation Trials
PERVs and Their Potential to Cause Xenozoonotic Disease
The Need to Screen for PERVs in Xenotransplantation
The Four Strategies to Prevent Transmission of PERVs
Careful Screening of the Source Pig Herd for PERVs
Qualitative Analysis of PERV DNA
Qualitative Analysis of PERV RNA
Detection of PERV by Hybridization Methods
Inhibition of PERV Expression by RNA Interference
Quantitative Analysis of PERV DNA and RNA
Determination of RT Activity
Selection of Pigs that Exhibit Low-Level Expression of PERV-A and PERV-B
Selection of Pigs That Do Not Contain PERV-C in Their Germ Line
Screening Xenotransplant Recipients—Molecular Biological Methods
Screening Xenotransplant Recipients—Immunochemical Methods
Findings
Closing Remarks
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