Latency-Associated Degradation of the MRP1 Drug Transporter During Latent Human Cytomegalovirus Infection
Open accessAbstract
Hide-and-Seek Virus: Human cytomegalovirus (HCMV) establishes latent infection in human progenitor dendritic cells, causing significant morbidity and mortality on reactivation, which may occur in transplantation patients who are immunosuppressed. Neither detection nor selective removal of rare latent HCMV-infected cells has been possible. Weekes et al. (p. 199 ) have found that the multidrug-resistant ABC transporter, multidrug resistance–associated protein-1 (MRP1) is down-regulated during latent HCMV infection. Consequently, cytotoxic MRP1-specific substrates are not exported from HCMV-infected cells and accumulate—leading to cell death, which could potentially provide a mechanism for eliminating infected cells prior to transplantation.
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In latent HCMV infection, the viral protein pUL138 degrades the PM drug transporter MRP1.
“More recently, during latent HCMV infection, the degradation of the PM drug transporter MRP1 by the viral protein pUL138 was discovered by SILAC-MS after PM enrichment (110).”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [110]
MRP1 loss made latently HCMV-infected monocytes and hematopoietic progenitors sensitive to cytotoxic MRP1 substrates.
“Loss of MRP1 conferred sensitivity to cytotoxic MRP1 drug substrates in latently infected monocytes and hematopoietic progenitors.”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [110]
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- Authors
- Weekes, M. P., Tan, S. Y. L., Poole, E., Talbot, S., Antrobus, R., Smith, D. L., Montag, C., Gygi, S. P., Sinclair, J. H., & Lehner, P. J.
- Affiliations
- University of Cambridge (GB)
- University of Manchester (GB)
- Charité – Universitätsmedizin Berlin (DE)
- Harvard University (US)
- Corresponding author
- Weekes, Michael P.
- Tan, Shireen Y. L.
- Poole, Emma
- Talbot, Suzanne
- Lehner, Paul J.
- ORCID
- Venue
- Science
- Published
- 2013-04-12
- Volume
- 340
- Issue
- 6129
- Pages
- 199-202
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3683642
- OpenAlex
- W2074715606
- Cited by
- 131
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 18 · 2020: 9 · 2019: 12 · 2018: 8 · 2017: 8 · 2016: 13 · 2015: 16 · 2014: 20 · 2013: 10
- FWCI
- 14.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (093966, 084957, 093966/Z/10/Z, 100140, 084957/Z/08/Z)
- Medical Research Council (MR/K021087/1)
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Keywords
- human cytomegalovirus, viral latency, MRP1, multidrug resistance-associated protein, drug transporters, myeloid progenitor cells, CD14+ cells, CD34+ cells, stable isotope labeling
- MeSH terms
- Cytomegalovirus Infections, Cytomegalovirus, Dendritic Cells, Humans, Lysosomes, Monocytes, Vincristine, Viral Proteins, Down-Regulation, Virus Latency, Antigens, CD34, ATP-Binding Cassette, Sub-Family C Proteins, Cell Line, Tumor, Monocyte-Macrophage Precursor Cells
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