Download kathleen switzer9/9/2023 ![]() To date, however, graft survival in NHP models has been relatively limited, principally due to the chronic cell damage from natural antibodies (NAb) present in human serum that recognize galactose α1-3 galactose (Gal) epitopes present on pig cells ( 22). Organs and tissues from pigs have the potential to relieve this shortage, since they are available in essentially unlimited quantities, and porcine grafts survive with life-supporting function in nonhuman primate (NHP) models ( 22). Complete inactivation of Gal-positive PERV particles was not achievable despite the use of high levels of NAb, indicating that NAb-mediated inactivation of cell-free PERV particles is an inefficient process.Ī serious donor organ shortage limits human organ and cell transplantation as a therapy for end-stage organ disease and diabetes mellitus. ![]() In contrast, although Gal-positive PERV particles were sensitive to inactivation by NAb and human serum, they required markedly higher concentrations of NAb for inactivation compared to the Gal-positive cells from which they were produced. ![]() PERV produced in Gal-null pig cells was resistant to inactivation by either NAb or human serum. We investigated the sensitivity of porcine endogenous retrovirus (PERV) produced from Gal-null and Gal-positive pig cells to inactivation by purified NAb and human serum. Concerns have been raised that the risk of virus transmission from such pigs may be increased due to the absence of the Gal sugars. The cells of these pigs do not express Gal sugars on their surface, i.e., are Gal null. Recently, pigs have been generated that possess disrupted galactosyl-transferase ( GGTA1) genes. The recognition of Gal sugars by natural anti-Gal antibodies (NAb) in human and Old World primate serum can cause the lysis of the particles via complement-dependent mechanisms and has therefore been proposed as an important antiviral mechanism. Galactose α1-3 galactose (Gal) trisaccharides are present on the surface of wild-type pig cells, as well as on viruses particles produced from such cells. ![]()
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