Nef-mediated down-regulation of CD4 and HLA class I in HIV-1 subtype C infection: association with disease progression and influence of immune pressure.
Nef-mediated down-regulation of CD4 and HLA class I in HIV-1 subtype C infection: association with disease progression and influence of immune pressure.
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DOI：
10.1016/j.virol.2014.08.009
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发表时间：
2014-11
期刊：
影响因子：
3.7
通讯作者：
Ndung'u, Thumbi
中科院分区：
文献类型：
--
作者：
Mann, Jaclyn K.;Chopera, Denis;Omarjee, Saleha;Kuang, Xiaomei T.;Le, Anh Q.;Anmole, Gursev;Danroth, Ryan;Mwimanzi, Philip;Reddy, Tarylee;Carlson, Jonathan;Radebe, Mopo;Goulder, Philip J. R.;Walker, Bruce D.;Karim, Salim Abdool;Novitsky, Vladimir;Williamson, Carolyn;Brockman, Mark A.;Brumme, Zabrina L.;Ndung'u, Thumbi
关键词：
Nef在HIV-1致病性中起主要作用。我们研究了HIV-1亚型C感染者的急性/早期（n=120）或慢性（n=207）感染，以研究Nef介导的CD 4/HLA-I下调活性与疾病进展之间的关系，以及免疫驱动的序列变异对这些Nef功能的影响。将每个个体的单个Nef序列克隆到表达质粒中，随后转染T细胞系并测量CD 4和HLA-I表达。在感染早期，观察到与较高病毒载量设定点相关的较高CD 4下调能力的趋势（r=0.19，p=0.05），并且较高HLA-I下调活性与较快的CD 4下降速率显著相关（p=0.02）。HLA-I下调功能与HLA相关多态性的数量呈负相关，这些多态性先前与选择性HLA等位基因缺失时的逆转相关（r=-0.21，p=0.0002）。这些数据支持在设计用于减弱感染过程的HIV-1疫苗策略中考虑某些Nef区域。
Nef plays a major role in HIV-1 pathogenicity. We studied HIV-1 subtype C infected individuals in acute/early (n=120) or chronic (n=207) infection to investigate the relationship between Nef-mediated CD4/HLA-I down-regulation activities and disease progression, and the influence of immune-driven sequence variation on these Nef functions. A single Nef sequence per individual was cloned into an expression plasmid, followed by transfection of a T cell line and measurement of CD4 and HLA-I expression. In early infection, a trend of higher CD4 down-regulation ability correlating with higher viral load set point was observed (r=0.19, p=0.05), and higher HLA-I down-regulation activity was significantly associated with faster rate of CD4 decline (p=0.02). HLA-I down-regulation function correlated inversely with the number HLA-associated polymorphisms previously associated with reversion in the absence of the selecting HLA allele (r=−0.21, p=0.0002). These data support consideration of certain Nef regions in HIV-1 vaccine strategies designed to attenuate the infection course.
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影响因子：
3.7
作者：
Adland E;Carlson JM;Paioni P;Kløverpris H;Shapiro R;Ogwu A;Riddell L;Luzzi G;Chen F;Balachandran T;Heckerman D;Stryhn A;Edwards A;Ndung'u T;Walker BD;Buus S;Goulder P;Matthews PC
通讯作者：
Matthews PC
DOI：
10.1126/science.1254031
发表时间：
2014-07-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carlson JM;Schaefer M;Monaco DC;Batorsky R;Claiborne DT;Prince J;Deymier MJ;Ende ZS;Klatt NR;DeZiel CE;Lin TH;Peng J;Seese AM;Shapiro R;Frater J;Ndung'u T;Tang J;Goepfert P;Gilmour J;Price MA;Kilembe W;Heckerman D;Goulder PJ;Allen TM;Allen S;Hunter E
通讯作者：
Hunter E
影响因子：
64.5
作者：
KESTLER, HW;RINGLER, DJ;DESROSIERS, RC
通讯作者：
DESROSIERS, RC
影响因子：
5.4
作者：
Brockman, Mark A.;Schneidewind, Arne;Allen, Todd M.
通讯作者：
Allen, Todd M.
影响因子：
56.9
作者：
DEACON, NJ;TSYKIN, A;MILLS, J
通讯作者：
MILLS, J