Porcine endogenous retrovirus (PERV) may potentially be transmitted through porcine xenotransplantation products administered to humans. This study examined the feasibility of using guinea pigs as a model to characterize the in vivo infectivity of PERV. To enhance the susceptibility of guinea pigs to retroviral infection or genomic integration, moderate physiological or immunological changes were induced prior to exposing the animals to PERV. Quantitative PERV-specific PCR performed on all tested samples resulted in either undetectable or very low copy numbers of proviruses, even in animals possessing PERV-specific antibody responses. The low copy number of viral DNA detected suggests that PERV infected a limited number of cells. However, PERV DNA levels did not increase over time, suggesting no virus replication occurred. These results in the guinea pig are similar to previous observations of non-human primate cells that allow PERV infection but do not support PERV replication in vitro.
ArgawT.,
RitzhauptA.,
WilsonC. A.2002; Development of a real time quantitative PCR assay for detection of porcine endogenous retrovirus. J Virol Methods 106:97–106
Xenotransplantation Subcommittee.2000; Report of the Food and Drug Administration Subcommittee on Xenotransplantation: meeting of 13 January 2000, Center for Biologics and Evaluation and Research. Xenotransplantation 7:75–79
DengY. M.,
TuchB. E.,
RawlinsonW. D.2000; Transmission of porcine endogenous retroviruses in severe combined immunodeficient mice xenotransplanted with fetal porcine pancreatic cells. Transplantation 70:1010–1016
ForbesS. J.,
ThemisM.,
AlisonM. R.,
SeldenC.,
CoutelleC.,
HodgsonH. J.1998; Retroviral gene transfer to the liver in vivo during tri-iodothyronine induced hyperplasia. Gene Ther 5:552–555
HeneineW.,
TibellA.,
SwitzerW. M.7 other authors1998; No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts. Lancet 352:695–699
JilbertA. R.,
BottenJ. A.,
MillerD. S.,
BertramE. M.,
HallP. M.,
KotlarskiJ.,
BurrellC. J.1998; Characterization of age- and dose-related outcomes of duck hepatitis B virus infection. Virology 244:273–282
KozlowskiP. A.,
BlackK. P.,
ShenL.,
JacksonS.1995; High prevalence of serum IgA HIV-1 infection-enhancing antibodies in HIV-infected persons. Masking by IgG. J Immunol 154:6163–6173
LaiL.,
Kolber-SimondsD.,
ParkK. W.11 other authors2002; Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295:1089–1092
LidburyB. A.,
MahalingamS.2000; Specific ablation of antiviral gene expression in macrophages by antibody-dependent enhancement of Ross River virus infection. J Virol 74:8376–8381
LossM.,
ArendsH.,
WinklerM.7 other authors2001; Analysis of potential porcine endogenous retrovirus (PERV) transmission in a whole-organ xenotransplantation model without interfering microchimerism. Transpl Int 14:31–37
MartinU.,
WinklerM. E.,
IdM.7 other authors2000; Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV). Xenotransplantation 7:138–142
MorensD. M.,
HalsteadS. B.1990; Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies. J Gen Virol 71:2909–2914
OlsenC. W.1993; A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and vaccination. Vet Microbiol 36:1–37
ParadisK.,
LangfordG.,
LongZ.7 other authors1999; Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group. Science 285:1236–1241
PatienceC.,
PattonG. S.,
TakeuchiY.,
WeissR. A.,
McClureM. O.,
RydbergL.,
BreimerM. E.1998; No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneys. Lancet 352:699–701
RettingerS. D.,
KennedyS. C.,
WuX.,
SaylorsR. L.,
HafenrichterD. G.,
FlyeM. W.,
PonderK. P.1994; Liver-directed gene therapy: quantitative evaluation of promoter elements by using in vivo retroviral transduction. Proc Natl Acad Sci U S A 91:1460–1464
RitzhauptA.,
Van Der LaanL. J.,
SalomonD. R.,
WilsonC. A.2002; Porcine endogenous retrovirus infects but does not replicate in nonhuman primate primary cells and cell lines. J Virol 76:11312–11320
SchumacherJ. M.,
ElliasS. A.,
PalmerE. P.12 other authors2000; Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology 54:1042–1050
SpeckeV.,
TackeS. J.,
BollerK.,
SchwendemannJ.,
DennerJ.2001; Porcine endogenous retroviruses: in vitro host range and attempts to establish small animal models. J Gen Virol 82:837–844
SwitzerW. M.,
MichlerR. E.,
ShanmugamV.13 other authors2001; Lack of cross-species transmission of porcine endogenous retrovirus infection to nonhuman primate recipients of porcine cells, tissues, or organs. Transplantation 71:959–965
TackeS. J.,
BoduschK.,
BergA.,
DennerJ.2001; Sensitive and specific immunological detection methods for porcine endogenous retroviruses applicable to experimental and clinical xenotransplantation. Xenotransplantation 8:125–135
TakeuchiY.,
PatienceC.,
MagreS.,
WeissR. A.,
BanerjeeP. T.,
Le TissierP.,
StoyeJ. P.1998; Host range and interference studies of three classes of pig endogenous retrovirus. J Virol 72:9986–9991
TodaroG. J.,
BenvenisteR. E.,
LieberM. M.,
SherrC. J.1974; Characterization of a type C virus released from the porcine cell line PK(15). Virology 58:65–74
TuckerA.,
BelcherC.,
MolooB.,
BellJ.,
MazzulliT.,
HumarA.,
HughesA.,
McArdleP.,
TalbotA.2002; The production of transgenic pigs for potential use in clinical xenotransplantation: baseline clinical pathology and organ size studies. Xenotransplantation 9:203–208
van der LaanL. J.,
LockeyC.,
GriffethB. C.8 other authors2000; Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice. Nature 407:90–94
WilsonC. A.,
EidenM. V.1991; Viral and cellular factors governing hamster cell infection by murine and gibbon ape leukemia viruses. J Virol 65:5975–5982
WilsonC. A.,
WongS.,
MullerJ.,
DavidsonC. E.,
RoseT. M.,
BurdP.1998; Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells. J Virol 72:3082–3087
YinL.,
LynchD.,
SellS.1999; Participation of different cell types in the restitutive response of the rat liver to periportal injury induced by allyl alcohol. J Hepatol 31:497–507