Modest attenuation of HIV-1 Vpu alleles derived from elite controller plasma.
Modest attenuation of HIV-1 Vpu alleles derived from elite controller plasma.
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DOI：
10.1371/journal.pone.0120434
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Fackler OT
中科院分区：
文献类型：
--
作者：
Chen J;Tibroni N;Sauter D;Galaski J;Miura T;Alter G;Mueller B;Haller C;Walker BD;Kirchhoff F;Brumme ZL;Ueno T;Fackler OT
在没有抗逆转录病毒疗法的情况下，感染1型人类免疫缺陷病毒（HIV-1）的感染通常不能被受感染的宿主控制，并导致获得性免疫缺陷的发展。然而，在极少数情况下，患者自发地控制HIV-1复制。这些精英控制者（EC）实现HIV-1复制控制的机制包括特别有效的免疫应答以及特定病毒株的适应性降低。为了解决是否在辅助HIV-1蛋白Vpu多态性与EC状态，我们功能分析了一组血浆来源的Vpu等位基因从15 EC和16慢性进展（CP）患者。内在免疫因子CD 317/tetherin对HIV颗粒释放限制的拮抗作用在EC和CP Vpu等位基因中很好地保守，强调了这种Vpu功能在HIV-1感染者中的选择性优势。相比之下，两组对CD 317/tetherin诱导的NF-κB活化的干扰几乎没有保留。EC Vpus更频繁地显示下调CD 4和MHC I类（MHC-I）分子以及NK细胞配体NTB-A的细胞表面水平的能力降低。与抑制性杀伤免疫球蛋白样受体（KIR）KIR 2DL 2的高亲和力相互作用潜在相关的多态性在EC Vpus中显著富集，但不能解释这些功能差异。总之，这些结果表明，在EC患者的亚组中，一些Vpu功能适度降低，可能是宿主选择的结果。
In the absence of antiretroviral therapy, infection with human immunodeficiency virus type 1 (HIV-1) can typically not be controlled by the infected host and results in the development of acquired immunodeficiency. In rare cases, however, patients spontaneously control HIV-1 replication. Mechanisms by which such elite controllers (ECs) achieve control of HIV-1 replication include particularly efficient immune responses as well as reduced fitness of the specific virus strains. To address whether polymorphisms in the accessory HIV-1 protein Vpu are associated with EC status we functionally analyzed a panel of plasma-derived vpu alleles from 15 EC and 16 chronic progressor (CP) patients. Antagonism of the HIV particle release restriction by the intrinsic immunity factor CD317/tetherin was well conserved among EC and CP Vpu alleles, underscoring the selective advantage of this Vpu function in HIV-1 infected individuals. In contrast, interference with CD317/tetherin induced NF-κB activation was little conserved in both groups. EC Vpus more frequently displayed reduced ability to downregulate cell surface levels of CD4 and MHC class I (MHC-I) molecules as well as of the NK cell ligand NTB-A. Polymorphisms potentially associated with high affinity interactions of the inhibitory killer immunoglobulin-like receptor (KIR) KIR2DL2 were significantly enriched among EC Vpus but did not account for these functional differences. Together these results suggest that in a subgroup of EC patients, some Vpu functions are modestly reduced, possibly as a result of host selection.
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DOI：
10.1097/qai.0b013e3181fe9450
发表时间：
2011-02-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Brumme ZL;Li C;Miura T;Sela J;Rosato PC;Brumme CJ;Markle TJ;Martin E;Block BL;Trocha A;Kadie CM;Allen TM;Pereyra F;Heckerman D;Walker BD;Brockman MA
通讯作者：
Brockman MA
影响因子：
6.7
作者：
Estrabaud, Emilie;Le Rouzic, Erwann;Margottin-Goguet, Florence
通讯作者：
Margottin-Goguet, Florence
影响因子：
30.3
作者：
Goffinet, Christine;Allespach, Ina;Keppler, Oliver T.
通讯作者：
Keppler, Oliver T.
影响因子：
64.5
作者：
AIKEN, C;KONNER, J;TRONO, D
通讯作者：
TRONO, D
影响因子：
56.9
作者：
DEACON, NJ;TSYKIN, A;MILLS, J
通讯作者：
MILLS, J