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How understanding immunology contributes to managing CMV disease in immunosuppressed patients: now and in future

Abstract

Several decades of research on human cytomegalovirus (HCMV) and the principal mammalian cytomegaloviruses which to varying degrees act as models of HCMV infection, particularly murine, guinea pig and rhesus CMV, have led to the recognition of the CMVs as interesting models of persistent infection with a large and complex DNA virus, which have been highly informative of the immunology and molecular pathogenesis of the virus–host relationship in the normal host. However, it is appropriate to ask how this relative wealth of knowledge has influenced the understanding and management of clinical disease due to HCMV. This article considers the immunology of cytomegalovirus in the normal human host, and the interrelated issue of the sites of HCMV latency and mechanisms of reactivation in the myeloid cell lineage, and in related in vitro model systems. The way in which this site of latency conditions the immune response, and emerging information on the special features of the adaptive immune response to HCMV during latency are also considered. Examples of HCMV disease associated with acquired immunosuppression, principally in the context of transplantation, but also as a consequence of HIV/AIDS and immune reconstitution inflammatory syndrome, are then discussed, with a particular emphasis on how understanding the immunology of persistent infection may contribute to managing CMV disease now and in future.

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Acknowledgments

The author wishes to acknowledge the generosity of close colleagues in Cambridge who have allowed him to talk about their work, in particular John Sinclair, Matt Reeves, Paul Lehner and Michael Weekes, and all the members of their groups who contributed to the work on HCMV, the long-standing Programme Grant support from the Medical Research Council and Fellowship support of the Wellcome Trust. He apologises for the limited citations of the extensive clinical and experimental literature that has contributed so much to understanding CMV biology and disease.

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to J.G. Patrick Sissons.

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This article is part of the Special Issue on Cytomegalovirus.

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Sissons, J., Wills, M.R. How understanding immunology contributes to managing CMV disease in immunosuppressed patients: now and in future. Med Microbiol Immunol 204, 307–316 (2015). https://doi.org/10.1007/s00430-015-0415-0

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Keywords

  • Human cytomegalovirus
  • Latency
  • Reactivation
  • T cells
  • NK cells
  • Immunoevasion