[转移帖]Nat.Med：抑制NPC1L1表达或可预防丙肝病毒感染
原帖由ipsvirus 发表于 2012-1-10 14:43 ：最新一期的Nature Medicine上发表了日本广岛大学和美国伊利诺伊大学研究人员组成的联合研究小组最新发现，人体中的NPC1L1蛋白在丙肝病毒感染过程中发挥了重要作用，遏制这种蛋白质的功能，可能有助于预防感染丙肝病毒。
该联合研究小组发现，一种代号为“NPC1L1”的人体蛋白质会在丙肝病毒感染过程中扮演受体角色，它能与丙肝病毒结合从而引发感染。“如果能阻止NPC1L1蛋白质发挥作用，就能使丙肝病毒的感染效率显著降低，将来有望据此开发出新的丙肝防治方法，”研究人员说。
NPC1L1是一类与NPC1同源的蛋白，存在于肝脏和小肠的细胞上。此前的研究发现，在其他蛋白质的帮助下，NPC1L1可以将食物中的胆固醇转运到细胞，再储存在肝脏中。由于NPC1L1吸收胆固醇的功能，医学界已经开发出通过遏制NPC1L1蛋白质发挥作用来治疗高血脂症的药物依泽替米贝。
此次研究小组在利用人体细胞进行实验时，将这种药物添加到丙肝病毒中，结果发现经过一段时间后，无论丙肝病毒属于哪种基因类型，其数量都减少了。此外，研究小组还将人体肝细胞移植到小鼠体内，然后再投放依泽替米贝，结果即使给小鼠注射丙肝病毒，也能遏制感染。
不过研究人员同时指出，通过遏制这种蛋白质的作用对抗丙肝病毒感染的效果还有待进一步研究确认。
（生物谷Bioon.com）
Identification of the Niemann-Pick C1–like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor
Bruno Sainz Jr,Naina Barretto,Danyelle N Martin,Nobuhiko Hiraga,Michio Imamura,Snawar Hussain,Katherine A Marsh,Xuemei Yu,Kazuaki Chayama,Waddah A Alrefai& Susan L Uprichard
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. With ~170 million individuals infected and current interferon-based treatment having toxic side effects and marginal efficacy, more effective antivirals are crucially needed. Although HCV protease inhibitors were just approved by the US Food and Drug Administration (FDA), optimal HCV therapy, analogous to HIV therapy, will probably require a combination of antivirals targeting multiple aspects of the viral lifecycle. Viral entry represents a potential multifaceted target for antiviral intervention; however, to date, FDA-approved inhibitors of HCV cell entry are unavailable. Here we show that the cellular Niemann-Pick C1–like 1 (NPC1L1) cholesterol uptake receptor is an HCV entry factor amendable to therapeutic intervention. Specifically, NPC1L1 expression is necessary for HCV infection, as silencing or antibody-mediated blocking of NPC1L1 impairs cell culture–derived HCV (HCVcc) infection initiation. In addition, the clinically available FDA-approved NPC1L1 antagonist ezetimibe potently blocks HCV uptake in vitro via a virion cholesterol–dependent step before virion-cell membrane fusion. Moreover, ezetimibe inhibits infection by all major HCV genotypes in vitro and in vivo delays the establishment of HCV genotype 1b infection in mice with human liver grafts. Thus, we have not only identified NPC1L1 as an HCV cell entry factor but also discovered a new antiviral target and potential therapeutic agent.
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