Latency-Associated Degradation of the MRP1 Drug Transporter During Latent Human Cytomegalovirus Infection

Author:

Weekes Michael P.1,Tan Shireen Y. L.1,Poole Emma2,Talbot Suzanne1,Antrobus Robin1,Smith Duncan L.3,Montag Christina4,Gygi Steven P.5,Sinclair John H.2,Lehner Paul J.1

Affiliation:

1. Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.

2. Department of Medicine, University of Cambridge Clinical School, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, UK.

3. Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Withington, Manchester M20 4BX, UK.

4. Laboratory for Molecular Biology, Children's Hospital, Charite Universitatsmedizin Berlin, Ziegelstrasse 5-9, D-10117 Berlin, Germany.

5. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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