Natural protection from zoonosis by alpha-gal epitopes on virus particles in xenotransmission.
Clinical transplantation has become one of the preferred treatments for end-stage organ failure, and one of the novel approaches being pursued to overcome the limited supply of human organs involves the use of organs from other species. The pig appears to be a near ideal animal due to proximity to humans, domestication, and ability to procreate. The presence of Gal-alpha1,3-Gal residues on the surfaces of pig cells is a major immunological obstacle to xenotransplantation. Alpha1,3galactosyltransferase (alpha1,3GT) catalyzes the synthesis of Gal alpha 1-3Gal beta 1-4GlcNAc-R (alpha-gal epitope) on the glycoproteins and glycolipids of non-primate mammals, but this does not occur in humans. Moreover, the alpha-gal epitope causes hyperacute rejection of pig organs in humans, and thus, the elimination of this antigen from pig tissues is highly desirable. Recently, concerns have been raised that the risk of virus transmission from such pigs may be increased due to the absence of alpha-gal on their viral particles. In this study, transgenic cells expressing alpha1,3GT were selected using 1.25 mg/ml neomycin. The development of HeLa cells expressing alpha1,3GT now allows accurate studies to be conducted on the function of the alpha-gal epitope in xenotransmission. The expressions of alpha-gal epitopes on HeLa/alpha-gal cells were demonstrated by flow cytometry and confocal microscopy using cells stained with IB4-fluorescein isothiocyanate lectin. Vaccinia viruses propagated in HeLa/alpha-gal cells also expressed alpha-gal on their viral envelopes and were more sensitive to inactivation by human sera than vaccinia virus propagated in HeLa cells. Moreover, neutralization of vaccinia virus was inhibited in human serum by 10 mm ethylene glycol bis(beta-aminoethylether)tetraacetic acid (EDTA) treatment. Our data indicated that alpha-gal epitopes are one of the major barriers to zoonosis via xenotransmission.
Kim
Na Young
NY
Department of Animal Biotechnology, Konkuk University, Seoul, Korea.
Jung
Woon-Won
WW
Oh
Yu-Kyung
YK
Chun
Taehoon
T
Park
Hong-Yang
HY
Lee
Hoon-Taek
HT
Han
In-Kwon
IK
Yang
Jai Myung
JM
Kim
Young Bong
YB
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D005700:Galactosyltransferases / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D013552:Swine; D014162:Transfection; D014183:Transplantation, Heterologous / Q000276:immunology*; D014312:Trisaccharides / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology; D014771:Virion / Q000276:immunology*; D014779:Virus Replication; D015047:Zoonoses / Q000635:transmission* / Q000821:virology
D000914:Antibodies, Viral; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase