Latency, Chromatin Remodeling, and Reactivation of Human Cytomegalovirus in the Dendritic Cells of Healthy Carriers

Human cytomegalovirus (HCMV) persists as a subclinical, lifelong infection in the normal human host, but reactivation from latency in immunocompromised subjects results in serious disease. Latency and reactivation are defining characteristics of the herpesviruses and are key to understanding their b...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 102; no. 11; pp. 4140 - 4145
Main Authors Reeves, M. B., MacAry, P. A., Lehner, P. J., Sissons, J. G. P., Sinclair, J. H., Kieff, Elliott D.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 15.03.2005
National Acad Sciences
Subjects
Antigens, CD34 - metabolism
Biological Sciences
Blotting, Western
Carrier State - metabolism
Carrier State - virology
Cellular differentiation
Chromatin
Chromatin Assembly and Disassembly - physiology
Cytomegalovirus - genetics
Cytomegalovirus - metabolism
Dendritic Cells - metabolism
Dendritic Cells - virology
DNA
DNA, Viral - metabolism
Gene expression
Hematopoietic Stem Cells - metabolism
Hematopoietic Stem Cells - virology
Herpes viruses
Histone Deacetylase 1
Histone Deacetylases - metabolism
Histones
Human cytomegalovirus
Humans
Microbiology
Monocytes
Monocytes - metabolism
Polymerase chain reaction
Renovations
Stem cells
Viruses
Online AccessGet full text

Cover

More Information
Summary:Human cytomegalovirus (HCMV) persists as a subclinical, lifelong infection in the normal human host, but reactivation from latency in immunocompromised subjects results in serious disease. Latency and reactivation are defining characteristics of the herpesviruses and are key to understanding their biology; however, the precise cellular sites in which HCMV is carried and the mechanisms regulating its latency and reactivation during natural infection remain poorly understood. Here we present evidence, based entirely on direct analysis of material isolated from healthy virus carriers, to show that myeloid dendritic cell (DC) progenitors are sites of HCMV latency and that their ex vivo differentiation to a mature DC phenotype is linked with reactivation of infectious virus resulting from differentiation-dependent chromatin remodeling of the viral major immediate-early promoter. Thus, myeloid DC progenitors are a site of HCMV latency during natural persistence, and there is a critical linkage between their differentiation to DC and transcriptional reactivation of latent virus, which is likely to play an important role in the pathogenesis of HCMV infection.
Bibliography:SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 14
ObjectType-Article-2
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
To whom correspondence should be addressed. E-mail: js@mole.bio.cam.ac.uk.
Author contributions: M.B.R., J.G.P.S., and J.H.S. designed research; M.B.R. performed research; P.A.M. contributed new reagents/analytic tools; M.B.R., P.J.L., J.G.P.S., and J.H.S. analyzed data; and M.B.R., P.J.L., J.G.P.S., and J.H.S. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: ChIP, chromatin immunoprecipitation; DC, dendritic cells; HCMV, human cytomegalovirus; HDAC, histone deacetylase; HF, human fibroblast; HP1, heterochromatin protein 1; IE, immediate-early; MIEP, major IE promoter.
Edited by Elliott D. Kieff, Harvard University, Boston, MA, and approved February 1, 2005
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0408994102