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免疫细胞的胆固醇代谢或和HIV感染进展直接相关

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近日,在加拿大温哥华举办的2015年HIV发病机制、疗法以及预防的第八届国际艾滋病协会会议上,来自国外的研究人员通过研究表示,特定免疫细胞中胆固醇水平较低或可帮助解释为何某些HIV感染者可以在自然情况下轻松控制疾病的发展,细胞中胆固醇水平较低意味着胆固醇代谢的增强。相关研究为科学家们通过调节细胞中胆固醇的代谢来理解控制HIV感染的策略提供了新的思路。

  近日,在加拿大温哥华举办的2015年HIV发病机制、疗法以及预防的第八届国际艾滋病协会会议上,来自国外的研究人员通过研究表示,特定免疫细胞中胆固醇水平较低或可帮助解释为何某些HIV感染者可以在自然情况下轻松控制疾病的发展,细胞中胆固醇水平较低意味着胆固醇代谢的增强。相关研究为科学家们通过调节细胞中胆固醇的代谢来理解控制HIV感染的策略提供了新的思路。
  名为抗原呈递细胞(APCs)的免疫细胞可以吸收HIV颗粒并且将完整感染性的病毒颗粒运输给T细胞,而这一过程是通过一种名为反式感染的非依赖性过程完成的;科学家们发现,来自于HIV无进展者机体的APCs并不会有效地反式感染T细胞,无进展者即是多年不进行抗病毒疗法而且疾病并无发展的HIV患者;这种反式感染的缺失或许是由于无进展者机体中APCs的胆固醇代谢增强所致。
  研究者Giovanna Rappocciolo表示,相关研究是通过对大量数据和样本进行研究所得,为了鉴别出和反式感染缺失相关的遗传因子,我们就追踪了基因表达的模式,或者特殊基因被关闭/开启的程度;研究者对8名HIV感染无进展者和8名HIV感染进展患者进行研究。
  相比疾病进展者而言,HIV感染无进展者机体的细胞会表达出较高水平的和反式感染缺失相关的多种胆固醇关联基因,而相关研究结果或许也可以帮助理解无进展者在不进行药物治疗的情况下控制HIV的机制,同时对于后期开发有效控制HIV感染的方法提供了新的思路和帮助。(转化医学网360zhyx.com)
  以上为转化医学网原创翻译整理,转载请注明出处和链接!
转化医学网推荐的原文摘要:

Cholesterol metabolism in immune cells linked to HIV progression

Immune cells known as antigen-presenting cells (APCs) can take up HIV particles and deliver intact, infectious virus to its primary target--T cells--through a replication-independent process known as trans infection. Scientists funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, found that APCs from nonprogressors--HIV-infected people whose disease does not progress for many years even without antiretroviral therapy--do not effectively trans infect T cells. A closer look revealed that this defect in trans infection is likely due to enhanced cholesterol metabolism within the nonprogressors' APCs, which appears to be an inherited trait.

These observations came from analysis of data and samples provided by participants in the NIH-supported Multicenter AIDS Cohort Study (MACS), a long-term study investigating the natural history of untreated and treated HIV/AIDS in men who have sex with men.

To identify genetic factors linked to defective trans infection, Giovanna Rappocciolo, Ph.D., of the University of Pittsburgh and colleagues searched for patterns in gene expression, or the degree to which specific genes are turned on or off, in APCs from eight HIV nonprogressors and eight progressors enrolled in MACS. Compared to APCs from progressors, cells from nonprogressors expressed higher levels of several cholesterol-related genes associated with defective trans infection. These results improve understanding of how nonprogressors control HIV without drug therapy and potentially may contribute to new approaches to manage HIV infection.

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