Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection.
Porcine endogenous retrovirus (PERV) is considered one of the major risks in xenotransplantation. No valid animal model has been established to evaluate the risks associated with PERV transmission to human patients by pig tissue xenotransplantation or to study the potential pathogenesis associated with PERV infection. In previous work we isolated two genes encoding functional human PERV receptors and proved that introduction of these into mouse fibroblasts allowed the normally nonpermissive mouse cells to become productively infected (T. A. Ericsson, Y. Takeuchi, C. Templin, G. Quinn, S. F. Farhadian, J. C. Wood, B. A. Oldmixon, K. M. Suling, J. K. Ishii, Y. Kitagawa, T. Miyazawa, D. R. Salomon, R. A. Weiss, and C. Patience, Proc. Natl. Acad. Sci. USA 100:6759-6764, 2003). In the present study we created mice transgenic for human PERV-A receptor 2 (HuPAR-2). After inoculation of transgenic animals with infectious PERV supernatants, viral DNA and RNA were detected at multiple time points, indicating productive replication. This establishes the role of HuPAR-2 in PERV infection in vivo; in addition, these transgenic mice represent a new model for determining the risk of PERV transmission and potential pathogenesis. These mice also create a unique opportunity to study the immune response to PERV infection and test potential therapeutic or preventative modalities.
Martina
Y
Y
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Marcucci
K T
KT
Cherqui
S
S
Szabo
A
A
Drysdale
T
T
Srinivisan
U
U
Wilson
C A
CA
Patience
C
C
Salomon
D R
DR
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D012192:Retroviridae Infections / Q000635:transmission* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine / Q000821:virology; D013997:Time Factors; D019076:Transgenes; D014779:Virus Replication
D004279:DNA, Viral; D012367:RNA, Viral; D011991:Receptors, Virus; D011994:Recombinant Proteins