Reduced sensitivity to human serum inactivation of enveloped viruses produced by pig cells transgenic for human CD55 or deficient for the galactosyl-alpha(1-3) galactosyl epitope.
Complement activation mediated by the major xenogeneic epitope in the pig, galactosyl-alpha(1-3) galactosyl sugar structure (alpha-Gal), and human natural antibodies could cause hyperacute rejection (HAR) in pig-to-human xenotransplantation. The same reaction on viruses bearing alpha-Gal may serve as a barrier to zoonotic infection. Expressing human complement regulatory proteins or knocking out alpha-Gal epitopes in pig in order to overcome HAR may therefore pose an increased risk in xenotransplantation with regard to zoonosis. We investigated whether amphotropic murine leukemia virus, porcine endogenous retrovirus, and vesicular stomatitis virus (VSV) budding from primary transgenic pig aortic endothelial (TgPAE) cells expressing human CD55 (hCD55 or hDAF) was protected from human-complement-mediated inactivation. VSV propagated through the ST-IOWA pig cell line, in which alpha-galactosyl-transferase genes were disrupted (Gal null), was also tested for sensitivity to human complement. The TgPAE cells were positive for hCD55, and all pig cells except the Gal-null ST-IOWA expressed alpha-Gal epitopes. Through antibody binding, we were able to demonstrate the incorporation of hCD55 onto VSV particles. Viruses harvested from TgPAE cells were relatively resistant to complement-mediated inactivation by the three sources of human sera tested. Additionally, VSV from Gal-null pig cells was resistant to human complement inactivation. Such protection of enveloped viruses may increase the risk of zoonosis from pigs genetically modified for pig-to-human xenotransplantation.
Magre
Saema
S
Wohl Virion Centre, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland St., London W1T 4JF, United Kingdom.
Takeuchi
Yasuhiro
Y
Langford
Gillian
G
Richards
Andrew
A
Patience
Clive
C
Weiss
Robin
R
D000818:Animals; D018958:CD55 Antigens / Q000502:physiology*; D003165:Complement System Proteins / Q000276:immunology*; D004187:Disaccharides / Q000502:physiology*; D020077:Endogenous Retroviruses / Q000276:immunology*; D042783:Endothelial Cells / Q000821:virology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000276:immunology*; D013552:Swine; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D018958:CD55 Antigens; D004187:Disaccharides; C055075:galactosyl-(1-3)galactose; D003165:Complement System Proteins