Publication Date:
2013-04-13
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683642/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683642/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weekes, Michael P -- Tan, Shireen Y L -- Poole, Emma -- Talbot, Suzanne -- Antrobus, Robin -- Smith, Duncan L -- Montag, Christina -- Gygi, Steven P -- Sinclair, John H -- Lehner, Paul J -- 084957/Wellcome Trust/United Kingdom -- 084957/Z/08/Z/Wellcome Trust/United Kingdom -- 093966/Wellcome Trust/United Kingdom -- 093966/Z/10/Z/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- G0701279/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Apr 12;340(6129):199-202. doi: 10.1126/science.1235047.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23580527" target="_blank"〉PubMed〈/a〉
Keywords:
Antigens, CD34/analysis
;
Cell Line, Tumor
;
Cytomegalovirus/genetics/*physiology
;
Cytomegalovirus Infections/*metabolism/*virology
;
Dendritic Cells/physiology
;
Down-Regulation
;
Humans
;
Lysosomes/metabolism
;
Monocyte-Macrophage Precursor Cells/metabolism/virology
;
Monocytes/metabolism/virology
;
Multidrug Resistance-Associated Proteins/genetics/*metabolism
;
Vincristine/metabolism/pharmacology
;
Viral Proteins/*metabolism
;
*Virus Latency
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
