HIV-1 Nef: at the crossroads.
HIV-1 Nef: at the crossroads.
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DOI：
10.1186/1742-4690-5-84
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发表时间：
2008-09-22
期刊：
影响因子：
3.3
通讯作者：
Garcia, J. Victor
中科院分区：
文献类型：
--
作者：
Foster, John L.;Garcia, J. Victor
抗病毒药物的发展减缓了艾滋病在西方世界的流行，但在全球范围内，艾滋病的流行并没有得到遏制。标准疫苗没有效果，由于安全问题，减毒疫苗也没有开发出来。对减毒疫苗的兴趣集中在感染含有缺失的nef基因的HIV-1的孤立病例。Nef是一种多功能的辅助蛋白，是HIV-1完全毒力所必需的。不幸的是，一些感染nef缺失病毒的患者最终失去了他们的CD 4 + T细胞，达到了表明进展为艾滋病的水平。这使得减毒的HIV-1仅基于nef缺失的可能性很小。在这篇综述中，我们将讨论从这些患者的研究和Nef功能的体外调查中获得的知识，以评估开发基于Nef的新的抗HIV-1药物的可能性。具体而言，我们认为CD 4下调，主要组织相容性复合物I下调，Pak 2激活，和增强病毒粒子的感染性。我们还考虑了最近的提议，即猴免疫缺陷病毒在其宿主中是非致病性的，因为它们具有下调CD 3的Nef，但HIV-1是致病性的，因为它的Nef未能下调CD 3。还考虑了将CD 3下调功能纳入HIV-1 Nef作为治疗选择的可能性。最后，我们得出结论，抑制CD 4下调功能是最有前途的Nef靶向方法，用于开发新的抗病毒药物，以对抗艾滋病。
The development of anti-virals has blunted the AIDS epidemic in the Western world but globally the epidemic has not been curtailed. Standard vaccines have not worked, and attenuated vaccines are not being developed because of safety concerns. Interest in attenuated vaccines has centered on isolated cases of patients infected with HIV-1 containing a deleted nef gene. Nef is a multifunctional accessory protein that is necessary for full HIV-1 virulence. Unfortunately, some patients infected with the nef-deleted virus eventually lose their CD4+ T cells to levels indicating progression to AIDS. This renders the possibility of an attenuated HIV-1 based solely on a deleted nef remote. In this review we discuss the knowledge gained both from the study of these patients and from in vitro investigations of Nef function to assess the possibility of developing new anti-HIV-1 drugs based on Nef. Specifically, we consider CD4 downregulation, major histocompatibility complex I downregulation, Pak2 activation, and enhancement of virion infectivity. We also consider the recent proposal that simian immunodeficiency viruses are non-pathogenic in their hosts because they have Nefs that downregulate CD3, but HIV-1 is pathogenic because its Nef fails to downregulate CD3. The possibility of incorporating the CD3 downregulation function into HIV-1 Nef as a therapeutic option is also considered. Finally, we conclude that inhibiting the CD4 downregulation function is the most promising Nef-targeted approach for developing a new anti-viral as a contribution to combating AIDS.
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影响因子：
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