Journal
SCIENCE
Volume 340, Issue 6129, Pages 199-202Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1235047
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Funding
- Cambridge Institute for Medical Research
- Wellcome Trust [093966/Z/10/Z, 084957/Z/08/Z]
- Agency for Science, Technology and Research, Singapore
- MRC [G0701279]
- NIHR Cambridge Biomedical Research Centre
- Medical Research Council [G0701279, MR/K021087/1] Funding Source: researchfish
- MRC [MR/K021087/1, G0701279] Funding Source: UKRI
- Wellcome Trust [084957/Z/08/Z, 093966/Z/10/Z] Funding Source: Wellcome Trust
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The reactivation of latent human cytomegalovirus (HCMV) infection after 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 require expression of the viral transcript UL138. Using 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 the 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 of which are 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 before transplantation.
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