Latency-associated degradation of the MRP1 drug transporter during latent human cytomegalovirus infection.
Latency-associated degradation of the MRP1 drug transporter during latent human cytomegalovirus infection.
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DOI：
10.1126/science.1235047
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发表时间：
2013-04-12
期刊：
影响因子：
--
通讯作者：
Lehner PJ
中科院分区：
文献类型：
--
作者：
Weekes MP;Tan SY;Poole E;Talbot S;Antrobus R;Smith DL;Montag C;Gygi SP;Sinclair JH;Lehner PJ
移植后潜伏的人巨细胞病毒（HCMV）感染的再激活与高发病率和死亡率相关。在体内，骨髓细胞及其祖细胞是HCMV潜伏的重要部位，其建立和/或维持需要UL 138的表达。使用基于SILAC（细胞培养物中氨基酸的稳定同位素标记）的质谱法，我们发现UL 138介导的细胞表面多药耐药相关蛋白-1（MRP 1）的显着丢失，以及该转运蛋白的底物输出减少。MRP 1的潜伏相关损失和细胞毒性药物长春新碱（一种MRP 1底物）的蓄积，从自然潜伏的CD 14+和CD 34+祖细胞中清除病毒，所有这些均为体内潜伏部位。UL 138介导的MRP 1缺失提供了用于检测潜伏性HCMV感染的标志物和用于在移植前消除潜伏性感染细胞的治疗靶标。
Reactivation of latent human cytomegalovirus (HCMV) infection following transplantation is associated with high morbidity and mortality. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, whose establishment and/or maintenance requires expression of UL138. Using SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry, we found a dramatic UL138-mediated loss of cell surface Multidrug Resistance-associated Protein-1 (MRP1), and reduction of substrate export by this transporter. Latency-associated loss of MRP1 and accumulation of the cytotoxic drug vincristine, an MRP1 substrate, depleted virus from naturally latent CD14+ and CD34+ progenitors, all in vivo sites of latency. The UL138-mediated loss of MRP1 provides a marker for detecting latent HCMV infection and a therapeutic target for eliminating latently-infected cells prior to transplantation.
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影响因子：
5.4
作者：
Petrucelli, Alex;Rak, Michael;Goodrum, Felicia
通讯作者：
Goodrum, Felicia
DOI：
10.1073/pnas.95.7.3937
发表时间：
1998-03-31
影响因子：
11.1
作者：
Hahn, G;Jores, R;Mocarski, ES
通讯作者：
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影响因子：
3.8
作者：
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通讯作者：
SINCLAIR, JH
影响因子：
4.4
作者：
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通讯作者：
Scheper, Rik J.
影响因子：
6.4
作者：
Jin, Jing;Jones, Arwyn T.
通讯作者：
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