Improved pig donor screening including newly identiﬁed variants
of porcine endogenous retrovirus-C (PERV-C)
Received: 22 May 2012 / Accepted: 16 August 2012 / Published online: 4 October 2012
Ó Springer-Verlag Wien 2012
Abstract Porcine endogenous retroviruses (PERV) are
widely distributed in the genomes of pigs. PERV-A and
PERV-B are present in all pigs. They infect human cells in
vitro and therefore represent a risk for xenotransplantation
when pig cells, tissues or organs are used. PERV-C infects
only pig cells and is not present in the genomes of all pigs.
However, PERV-A/C recombinants infecting human cells
and characterized by high replication titers were found in
pigs. To select PERV-C-free animals that cannot generate
such recombinants, PCR-based assays were developed
(Kaulitz et al., J Virol Methods, 175:60, 2011). When
screening for PERV-C in German wild boars (Sus scrofa
scrofa), applying these methods, a new variant of PERV-C
was identiﬁed. Whereas in all 125 wild boar only the new
variant of PERV-C was found, different variants were
present in some landrace pigs, and most importantly, some
pigs were totally free of PERV-C.
Porcine endogenous retroviruses (PERV) pose a special
risk in xenotransplantation using pig cells, tissues or organs
to overcome the shortage of human allotransplants .
Endogenous retroviruses have been detected in the gen-
omes of all vertebrate species, and their general organiza-
tion corresponds to that of exogenous retroviruses [2, 3].
Most of the endogenous retroviruses are replication
incompetent, while only a minority still produce infectious
virus particles that are able to infect cells of the same
(ecotropic) or of other species (polytropic, xenotropic) [4, 5].
In pigs, three different classes exist, PERV-A, PERV-B
and PERV-C, which all belong to the gammaretroviruses
[6–8]. In addition, betaretroviruses are also found in the
genomes of pigs . PERV-A and PERV-B infect human
cells in vitro as well as cells from other species [7, 10–13].
In contrast, PERV-C is an ecotropic virus infecting only
pig cells, and it is not present in the genomes of all pigs [6,
7]. PERVs may be the result of a transspecies transmission,
possibly of murine viruses to pigs . PERV-A integrated
into the pig genome approximately 7.6 million years ago
(MYA), whereas PERV-C integrated in S. barbatus
approximately 1.5 MYA .
In addition, replication-competent PERV-A/C recombi-
nants have been found in normal pigs [16–19] and in pigs
carrying melanomas . The recombinants were found de
novo integrated in the genome of somatic cells of these
animals, but they are not present in the germ line [16–22].
PERV-A/C isolates are characterized by high-titer repli-
cation and speciﬁc mutations when compared with the
parental PERV-A . After passaging on human cells, the
virus titer has been found to increase signiﬁcantly due to
genetic alterations in the LTR [23, 24]. Similar genetic
alterations in the LTR have also been detected in PERV-A
passaged in human cells [
23, 25]. A consensus statement of
the International Xenotransplantation Association has
suggested breeding pigs for xenotransplantation that do not
harbor PERV-C in order to avoid generating such high-titer
Electronic supplementary material The online version of this
article (doi:10.1007/s00705-012-1490-9) contains supplementary
material, which is available to authorized users.
D. Kaulitz Á D. Mihica Á M. Semaan Á J. Denner (&)
Centre of HIV and Retrovirology, Robert Koch-Institute,
Nordufer 20, 13353 Berlin, Germany
Center for Biological Security, ZBS1, Robert Koch-Institute,
Nordufer 20, 13353 Berlin, Germany
Arch Virol (2013) 158:341–348