Reduced Sensitivity to Human Serum Inactivation of Enveloped Viruses Produced by Pig Cells Transgenic for Human CD55 or Deficient for the Galactosyl-α(1-3) Galactosyl Epitope
| Autor: | Gillian Langford, Clive Patience, Saema Magre, Andrew Richards, Robin A. Weiss, Yasuhiro Takeuchi |
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| Rok vydání: | 2004 |
| Předmět: |
Swine
Xenotransplantation medicine.medical_treatment Immunology Disaccharides Microbiology Vesicular stomatitis Indiana virus Epitope Virology Murine leukemia virus medicine Animals Humans Decay-accelerating factor CD55 Antigens biology CD46 Endogenous Retroviruses Endothelial Cells Complement System Proteins biology.organism_classification Molecular biology Complement system Leukemia Virus Murine Vesicular stomatitis virus Insect Science biology.protein Pathogenesis and Immunity Antibody |
| Zdroj: | Journal of Virology. 78:5812-5819 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Complement activation mediated by the major xenogeneic epitope in the pig, galactosyl-α(1-3) galactosyl sugar structure (α-Gal), and human natural antibodies could cause hyperacute rejection (HAR) in pig-to-human xenotransplantation. The same reaction on viruses bearing α-Gal may serve as a barrier to zoonotic infection. Expressing human complement regulatory proteins or knocking out α-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 α-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 α-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. |
| Databáze: | OpenAIRE |
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