Sleepless latency of human cytomegalovirus.
Publication Date
2015-06Journal Title
Med Microbiol Immunol
ISSN
0300-8584
Publisher
Springer Verlag
Volume
204
Pages
421-429
Language
English
Type
Article
Metadata
Show full item recordCitation
Poole, E., & Sinclair, J. (2015). Sleepless latency of human cytomegalovirus.. Med Microbiol Immunol, 204 421-429. https://doi.org/10.1007/s00430-015-0401-6
Abstract
As with all human herpesviruses, human cytomegalovirus (HCMV) persists for the lifetime of the host by establishing a latent infection, which is broken by periodic reactivation events. One site of HCMV latency is in the progenitor cells of the myeloid lineage such as CD34+ cells and their CD14+ derivatives. The development of experimental techniques to isolate and culture these primary cells in vitro is enabling detailed analysis of the events that occur during virus latency and reactivation. Ex vivo differentiation of latently infected primary myeloid cells to dendritic cells and macrophages results in the reactivation of latent virus and provides model systems in which to analyse the viral and cellular functions involved in latent carriage and reactivation. Such analyses have shown that, in contrast to primary lytic infection or reactivation which is characterised by a regulated cascade of expression of all viral genes, latent infection is associated with a much more restricted viral transcription programme with expression of only a small number of viral genes. Additionally, concomitant changes in the expression of cellular miRNAs and cellular proteins occur, and this includes changes in the expression of a number of secreted cellular proteins and intracellular anti-apoptotic proteins, which all have profound effects on the latently infected cells. In this review, we concentrate on the effects of one of the latency-associated viral proteins, LAcmvIL-10, and describe how it causes a decrease in the cellular miRNA, hsa-miR-92a, and a concomitant upregulation of the GATA2 myeloid transcription factor, which, in turn, drives the expression of cellular IL-10. Taken together, we argue that HCMV latency, rather than a period of viral quiescence, is associated with the virally driven manipulation of host cell functions, perhaps every bit as complex as lytic infection. A full understanding of these changes in cellular and viral gene expression during latent infection could have far-reaching implications for therapeutic intervention.
Keywords
Latency, Human cytomegalovirus, Cell survival
Sponsorship
We thank the MRC for funding, Grant Number G0701279. This research was supported by the Cambridge NIHR BRC cell phenotyping hub.
Funder references
Medical Research Council (G0701279)
Medical Research Council (MR/K021087/1)
Identifiers
External DOI: https://doi.org/10.1007/s00430-015-0401-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/247764
Rights
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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