Quinn Gary, Wood James C, Ryan David J J, Suling Kristen M, Moran Kathleen M, Kolber-Simonds Donna L, Greenstein Julia L, Schuurman Henk-Jan, Hawley Robert J, Patience Clive
Immerge BioTherapeutics Inc., 300 Technology Sq., Cambridge, MA 02139, USA.
J Virol. 2004 Jun;78(11):5805-11. doi: 10.1128/JVI.78.11.5805-5811.2004.
Galactose alpha1-3 galactose (Gal) trisaccharides are present on the surface of wild-type pig cells, as well as on viruses particles produced from such cells. 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. Recently, pigs have been generated that possess disrupted galactosyl-transferase (GGTA1) genes. The cells of these pigs do not express Gal sugars on their surface, i.e., are Gal null. Concerns have been raised that the risk of virus transmission from such pigs may be increased due to the absence of the Gal sugars. 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. PERV produced in Gal-null pig cells was resistant to inactivation by either NAb or human serum. 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. 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.
α1-3半乳糖(Gal)三糖存在于野生型猪细胞表面,以及由此类细胞产生的病毒颗粒表面。人类和旧世界灵长类动物血清中的天然抗Gal抗体(NAb)对Gal糖的识别可通过补体依赖机制导致颗粒裂解,因此被认为是一种重要的抗病毒机制。最近,已培育出具有破坏的半乳糖基转移酶(GGTA1)基因的猪。这些猪的细胞表面不表达Gal糖,即Gal缺失。有人担心,由于缺少Gal糖,此类猪的病毒传播风险可能会增加。我们研究了Gal缺失和Gal阳性猪细胞产生的猪内源性逆转录病毒(PERV)对纯化的NAb和人血清灭活的敏感性。Gal缺失猪细胞产生的PERV对NAb或人血清的灭活具有抗性。相比之下,尽管Gal阳性PERV颗粒对NAb和人血清的灭活敏感,但与产生它们的Gal阳性细胞相比,它们需要明显更高浓度的NAb才能被灭活。尽管使用了高水平的NAb,Gal阳性PERV颗粒仍无法完全灭活,这表明NAb介导的无细胞PERV颗粒灭活是一个低效的过程。