Previously a strategy for monitoring of pigs intended for cell transplantation was developed and successfully applied to several representative herds in New Zealand. A designated pathogen-free (DPF) herd has been chosen as a good candidate for xenotransplantation. This herd has previously tested free of infectious agents relevant to xenotransplantation and we present here an in depth study of porcine endogenous retrovirus (PERV) transmission. A panel of assays that describes the constraints for the transmission of PERV has been suggested. It includes a) infectivity test in coculture of DPF pig primary cells with both human and pig target cell lines; b) RT activity in supernatant of stimulated primary cells from DPF pigs; c) viral load in donor's blood plasma; d) PERV proviral copy number in DPF pig genome; e) PERV class C prevalence in the herd and its recombination potential. There was no evidence of PERV transmission from DPF pig tissue to either pig or human cells. Additionally, there was no evidence of PERV RNA present in pig blood plasma. PERV copy number differs in individual pigs from as low as 3 copies to 30 copies and the presence of PERV-C varied between animals and breeds. In all DPF pigs tested, a specific locus for PERV-C potentially associated with the recombination of PERV in miniature swine was absent. Presented data on the PERV transmission allows us to classify the DPF potential donors as “null” or noninfectious pigs.
AkiyoshiD. E.; DenaroM.; ZhuH.; GreensteinJ. L.; BanerjeeP.; FishmanJ. A.Identification of a full-length cDNA for an endogenous retrovirus of miniature swine.J. Virol.72(5): 4503–4507; 1998.
2.
BartoschB.; StefanidisD.; MyersR.; WeissR.; PatienceC.; TakeuchiY.Evidence and consequence of porcine endogenous retrovirus recombination.J. Virol.78(24): 13880–13890; 2004.
3.
BoschS.; ArnauldC.; JestinA.Study of full-length porcine endogenous retrovirus genomes with envelope gene polymorphism in a specific-pathogen-free Large White swine herd.J. Virol.74(18): 8575–8581; 2000.
4.
ClemenceauB.; LalainS.; MartignatL.; SaiP.Porcine endogenous retroviral mRNAs in pancreas and a panel of tissues from specific pathogen-free pigs.Diabetes Metab.25(6): 518–525; 1999.
5.
CunninghamD. A.; Dos Santos CruzG. J.; Fernandez-SuarezX. M.; WhittamA. J.; HerringC.; CopemanL.; RichardsA.; LangfordG. A.Activation of primary porcine endothelial cells induces release of porcine endogenous retroviruses.Transplantation77(7): 1071–1079; 2004.
6.
DinsmoreJ. H.; ManhartC.; RaineriR.; JacobyD. B.; MooreA.No evidence for infection of human cells with porcine endogenous retrovirus (PERV) after exposure to porcine fetal neuronal cells.Transplantation70(9): 1382–1389; 2000.
7.
ElliottR. B.; EscobarL.; GarkavenkoO.; CroxsonM. C.; SchroederB. A.; McGregorM.; FergusonG.; BeckmanN.; FergusonS.No evidence of infection with porcine endogenous retrovirus in recipients of encapsulated porcine islet xenografts.Cell Transplant.9(6): 895–901; 2000.
GarkavenkoO.; MuzinaM.; MuzinaZ.; PowelsK.; ElliottR. B.; CroxsonM. C.Monitoring for potentially xenozoonotic viruses in New Zealand pigs.J. Med. Virol.72(2): 338–344; 2004.
11.
GorbovitskaiaM.; LiuZ.; BourgeauxN.; LiN.; LianZ.; ChardonP.; Rogel-GaillardC.Characterization of two porcine endogenous retrovirus integration loci and variability in pigs.Immunogenetics55(4): 262–270; 2003.
12.
HarrisonI.; TakeuchiY.; BartoschB.; StoyeJ. P.Determinants of high titer in recombinant porcine endogenous retroviruses.J. Virol.78(24): 13871–13879; 2004.
13.
HectorR. D.; MeikleS.; GrantL.; WilkinsonR. A.; FishmanJ. A.; ScobieL.Pre-screening of miniature swine may reduce the risk of transmitting human tropic recombinant porcine endogenous retroviruses.Xenotransplantation14(3): 222–226; 2007.
14.
HerringC.; QuinnG.; BowerR.; ParsonsN.; LoganN. A.; BrawleyA.; ElsomeK.; WhittamA.; Fernandez-SuarezX. M.; CunninghamD.; OnionsD.; LangfordG.; ScobieL.Mapping full-length porcine endogenous retroviruses in a large white pig.J. Virol.75(24): 12252–12265; 2001.
15.
LeeJ. H.; WebbG. C.; AllenR. D.; MoranC.Characterizing and mapping porcine endogenous retroviruses in Westran pigs.J. Virol.76(11): 5548–5556; 2002.
16.
LuQ.; HanH.; LianZ.; LiN.; ZhangQ.; ZhaoZ.; PeiD.; ZhangX.; WuC.The screening and identification of endogenous retrovirus free CEMPs.Sci. China C Life Sci.47(6): 562–566; 2004.
17.
MangR.; MaasJ.; ChenX.; GoudsmitJ.; van Der KuylA. C.Identification of a novel type C porcine endogenous retrovirus: Evidence that copy number of endogenous retroviruses increases during host inbreeding.J. Gen. Virol.82(Pt. 8): 1829–1834; 2001.
18.
MartinS. I.; WilkinsonR.; FishmanJ. A.Genomic presence of recombinant porcine endogenous retrovirus in transmitting miniature swine.J. Virol.3: 91–95; 2006.
19.
MartinU.; KiessigV.; BluschJ. H.; HaverichA.; von der HelmK.; HerdenT.; SteinhoffG.Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells.Lancet352(9129): 692–694; 1998.
20.
MartinU.; WinklerM. E.; IdM.; RadekeH.; ArsenievL.; TakeuchiY.; SimonA. R.; PatienceC.; HaverichA.; SteinhoffG.Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV).Xenotransplantation7(2): 138–142; 2000.
21.
NiebertM.; TonjesR. R.Analyses of prevalence and polymorphisms of six replication-competent and chromosomally assigned porcine endogenous retroviruses in individual pigs and pig subspecies.Virology313(2): 427–434; 2003.
22.
OldmixonB. A.; WoodJ. C.; EricssonT. A.; WilsonC. A.; White-ScharfM. E.; AnderssonG.; GreensteinJ. L.; SchuurmanH. J.; PatienceC.Porcine endogenous retrovirus transmission characteristics of an inbred herd of miniature swine.J. Virol.76(6): 3045–3048; 2002.
23.
PatienceC.; SwitzerW. M.; TakeuchiY.; GriffithsD. J.; GowardM. E.; HeneineW.; StoyeJ. P.; WeissR. A.Multiple groups of novel retroviral genomes in pigs and related species.J. Virol.75(6): 2771–2775; 2001.
24.
PatienceC.; TakeuchiY.; WeissR. A.Infection of human cells by an endogenous retrovirus of pigs.Nat. Med.3(3): 282–286; 1997.
25.
QuinnG.; WoodJ.; SulingK.; ArnS.; SachsD. H.; SchuurmanH. J.; PatienceC.Genotyping of porcine endogenous retroviruses from a family of miniature swine.J. Virol.78(1): 314–319; 2004.
26.
RodrigoA. G.Dynamics of syncytium-inducing and non-syncytium-inducing type 1 human immunodeficiency viruses during primary infection.AIDS Res. Hum. Retroviruses13(17): 1447–1451; 1997.
27.
ScobieL.; TaylorS.; WoodJ. C.; SulingK. M.; QuinnG.; MeikleS.; PatienceC.; SchuurmanH. J.; OnionsD. E.Absence of replication-competent human-tropic porcine endogenous retroviruses in the germ line DNA of inbred miniature swine.J. Virol.78(5): 2502–2509; 2004.
28.
SkinnerS. J.; GeaneyM. S.; RushR.; RogersM. L.; EmerichD. F.; ThanosC. G.; VasconcellosA. V.; TanP. L.; ElliotR. B.Choroid plexus transplants in the treatment of brain diseases.Xenotransplantation13(4): 284–288; 2006.
29.
SpeckeV.; RubantS.; DennerJ.Productive infection of human primary cells and cell lines with porcine endogenous retroviruses.Virology285(2): 177–180; 2001.
30.
TackeS. J.; SpeckeV.; DennerJ.Differences in release and determination of subtype of porcine endogenous retroviruses produced by stimulated normal pig blood cells.Intervirology46(1): 17–24; 2003.
31.
TakeuchiY.Retrovirus time travel.Trends Microbiol.6(11): 430; 1998.
32.
Tao-ShengL.; MikamoA.; TakahashiM.; SuzukiR.; UedaK.; IkedaY.; MatsuzakiM.; HamanoK.Comparison of cell therapy and cytokine therapy for functional repair in ischemic and nonischemic heart failure.Cell Transplant.16(4): 365–374; 2007.
33.
Valdes-GonzalezR. A.; WhiteD. J. G.; DorantesL. M.; TeranL.; Garibay-NietoG. N.; Bracho-BlanchetE.; Davila-PerezR.; Evia-ViscarraL.; OrmsbyC. E.; Ayala-SumuanoJ. T.; Silva-TorresM. L.; Ramirez-GonzalezB.Three-yr follow-up of a type 1 diabetes mellitus patient with an islet xenotransplant.Clin. Transplant.21(3): 352–357; 2007.
34.
WilsonC. A.; WongS.; MullerJ.; DavidsonC. E.; RoseT. M.; BurdP.Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells.J. Virol.72(4): 3082–3087; 1998.
35.
WilsonC. A.; WongS.; BrocklinM. V.; FederspielM. J.Extended analysis of the in vitro tropism of porcine endogenous retrovirus.J. Virol.74(1): 49–56; 2000.
36.
WoodJ. C.; QuinnG.; SulingK. M.; OldmixonB. A.; Van TineB. A.; CinaR.; ArnS.; HuangC. A.; ScobieL.; OnionsD. E.; SachsD. H.; SchuurmanH. J.; FishmanJ. A.; PatienceC.Identification of exogenous forms of human-tropic porcine endogenous retrovirus in miniature swine.J. Virol.78(5): 2494–2501; 2004.
