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丙型肝炎病毒的CD81结合区域在肝移植后仍保持保守。

CD81 binding regions of hepatitis C virus remain conserved after liver transplantation.

作者信息

Lyra Andre C, Fan Xiaofeng, Di Bisceglie Adrian M

机构信息

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.

出版信息

Braz J Infect Dis. 2004 Apr;8(2):126-32. doi: 10.1590/S1413-86702004000200002. Epub 2004 Sep 8.

Abstract

CD81 is a surface-associated protein expressed in the membranes of mammalian cells. It has been suggested that CD81 interacts with hepatitis C virus E2 protein, and thus might facilitate the entry of HCV into hepatocytes. The envelope-binding site appears to involve amino acids (aa) 480-493 and 544-551 within the E2 glycoprotein. Little is known about the quasispecies genetic diversity of these two regions. We studied four patients who underwent transplantation for HCV-related cirrhosis and who developed recurrent hepatitis C. We evaluated HCV quasispecies diversity in serum samples obtained at the time of transplantation and at several time points thereafter. Quasispecies diversity was assessed by cloning and sequencing of viral isolates, with computer analysis of evolution models. The genetic distance in the region that spans aa 480 to 493 was 0.019 +/- 0.004 before the transplant, and 0.039 +/- 0.014 after the transplant (p=0.324). In the aa 544 to 551 region, the pre-transplant genetic distance was 0.012 +/- 0.008 and the post-transplant distance, 0.010 +/- 0.007 (p=0.890). There was also no significant difference between the number of nonsynonymous substitutions per nonsynonymous site before and after transplantation. In conclusion, the HCV genetic sequences of putative CD81 binding regions aa 480-493 and aa 544-551 did not diversify significantly after liver transplantation. This may favor HCV re-infection of the allograft after liver transplantation.

摘要

CD81是一种在哺乳动物细胞膜中表达的表面相关蛋白。有人提出,CD81与丙型肝炎病毒E2蛋白相互作用,因此可能促进HCV进入肝细胞。包膜结合位点似乎涉及E2糖蛋白内的氨基酸(aa)480 - 493和544 - 551。关于这两个区域的准种遗传多样性知之甚少。我们研究了4例因HCV相关肝硬化接受移植且发生复发性丙型肝炎的患者。我们评估了移植时及此后几个时间点采集的血清样本中的HCV准种多样性。通过对病毒分离株进行克隆和测序,并对进化模型进行计算机分析来评估准种多样性。在跨越aa 480至493的区域,移植前的遗传距离为0.019±0.004,移植后的遗传距离为0.039±0.014(p = 0.324)。在aa 544至551区域,移植前的遗传距离为0.012±0.008,移植后的遗传距离为0.010±0.007(p = 0.890)。移植前后每个非同义位点的非同义替换数量之间也没有显著差异。总之,推测的CD81结合区域aa 480 - 493和aa 544 - 551的HCV基因序列在肝移植后没有显著多样化。这可能有利于肝移植后同种异体移植物的HCV再次感染。

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