Porcine Endogenous Retroviruses in Xenotransplantation—Molecular Aspects

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.

Porcine endogenous retrovirus-A/C: biochemical properties of its integrase and susceptibility to raltegravir

“…Thus, the risk of zoonotic transmission has raised serious biosafety concerns about the use of pig organs in human xenotransplantation programmes (Kimsa et al, 2014).…”

An association between type A porcine endogenous retrovirus copy number and hematological parameters and gender in miniature pigs

“…PERVA and PERVB infects not only porcine cell lines, but also several human cell lines in vitro, while PERVC replicates only in porcine cells (Kimsa et al, 2014). Observations of patients treated with living porcine tissues or organs have not yet revealed the development of PERV infection in humans in vivo (Godehardt et al, 2015).…”

Determination of the copy numbers of type A porcine endogenous retroviruses in domestic pigs and wild boars

“…Показано, что рекомбинанты PERV А/С также способны инфицировать клетки человека, причем их провирусы могут интегрироваться de novo в геномы соматических (но не герминативных) клеток (Denner, 2008;Karlas et al, 2010). Эксперименты доказали, что PERV могут инфицировать некоторые линии клеток человека in vitro (Specke et al, 2001;Lee et al, 2008;Yu et al, 2009;Kimsa et al, 2014). Перенос эндогенных ретровирусов свиньи и, в некоторых случаях, даже их репликация были продемонстрированы на культурах первичных эндотелиальных клеток, гепато-цитов и мононуклеарных клеток периферической крови человека (Specke et al, 2001;Li et al, 2006;Frühauf et al, 2009).…”

“…PERV A и B, помимо клеточных ли-ний свиньи, могут инфицировать некоторые линии клеток человека in vitro, а PERV C может реплицироваться только в клетках свиньи (Kimsa et al, 2014). Исследования боль-ных, которых лечили с использованием живых тканей или органов свиньи, до сих пор не выявили развития инфекции PERV у человека in vivo (Godehardt et al, 2015).…”