Takefman Daniel M, Spear Gregory T, Saifuddin Mohammed, Wilson Carolyn A
Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
J Virol. 2002 Feb;76(4):1999-2002. doi: 10.1128/jvi.76.4.1999-2002.2002.
Transgenic pigs have been engineered to express human CD59 (hCD59) in order to suppress hyperacute rejection of xenotransplants in human recipients. In this study, porcine endogenous retrovirus (PERV) was produced in a porcine cell line expressing hCD59 in order to examine the effect of this complement control protein on PERV neutralization by human sera. hCD59 was found to be incorporated into PERV particles produced from engineered ST-IOWA cells. PERV incorporation of hCD59 resulted in a dramatic inhibition of complement-mediated virolysis by human serum. However, incorporation of hCD59 had no effect on neutralization of PERV by human serum, as measured in infectivity assays. Our results suggest that the use of organs from hCD59 transgenic pigs will inhibit complement-mediated virolysis, but will not compromise the protective effects of human sera on the neutralization of PERV particles.
已对转基因猪进行基因改造,使其表达人CD59(hCD59),以抑制人类受者对异种移植的超急性排斥反应。在本研究中,为了检测这种补体控制蛋白对人血清中和猪内源性逆转录病毒(PERV)的影响,在表达hCD59的猪细胞系中产生了PERV。发现hCD59被整合到由工程化的ST - IOWA细胞产生的PERV颗粒中。hCD59整合到PERV中导致人血清对补体介导的病毒溶解有显著抑制作用。然而,如在感染性测定中所测量的,hCD59的整合对人血清中和PERV没有影响。我们的结果表明,使用来自hCD59转基因猪的器官将抑制补体介导的病毒溶解,但不会损害人血清对PERV颗粒中和的保护作用。