Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers

被引:278
作者
Reeves, MB
MacAry, PA
Lehner, PJ
Sissons, JGP
Sinclair, JH
机构
[1] Univ Cambridge, Sch Clin Med, Cambridge Inst Med Res, Cambridge CB2 2QQ, England
[2] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England
基金
英国医学研究理事会;
关键词
D O I
10.1073/pnas.0408994102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4140 / 4145
页数:6
相关论文
共 47 条
[1]  
ADLER SP, 1983, REV INFECT DIS, V5, P977
[2]  
Arrode G, 2003, CURR TOP MICROBIOL, V276, P277
[3]   Ets-2 Repressor Factor (ERF) mediates repression of the human cytomegalovirus major immediate-early promoter in undifferentiated non-permissive cells [J].
Bain, M ;
Mendelson, M ;
Sinclair, J .
JOURNAL OF GENERAL VIROLOGY, 2003, 84 :41-49
[4]   Immunobiology of dendritic cells [J].
Banchereau, J ;
Briere, F ;
Caux, C ;
Davoust, J ;
Lebecque, S ;
Liu, YT ;
Pulendran, B ;
Palucka, K .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :767-+
[5]   Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain [J].
Bannister, AJ ;
Zegerman, P ;
Partridge, JF ;
Miska, EA ;
Thomas, JO ;
Allshire, RC ;
Kouzarides, T .
NATURE, 2001, 410 (6824) :120-124
[6]   Developmental stage-specific epigenetic control of human β-globin gene expression is potentiated in hematopoietic progenitor cells prior to their transcriptional activation [J].
Bottardi, S ;
Aumont, A ;
Grosveld, F ;
Milot, E .
BLOOD, 2003, 102 (12) :3989-3997
[7]   LATENT CYTOMEGALOVIRUS INFECTION IN BLOOD DONORS [J].
DIOSI, P ;
MOLDOVAN, E ;
TOMESCU, N .
BRITISH MEDICAL JOURNAL, 1969, 4 (5684) :660-&
[8]   CYTOMEGALO-VIRUS INFECTION IN PATIENTS WITH AIDS [J].
DREW, WL .
JOURNAL OF INFECTIOUS DISEASES, 1988, 158 (02) :449-456
[9]   SPECIFIC INTERACTIONS BETWEEN TRANSCRIPTION FACTORS AND THE PROMOTER-REGULATORY REGION OF THE HUMAN CYTOMEGALO-VIRUS MAJOR IMMEDIATE-EARLY GENE [J].
GHAZAL, P ;
LUBON, H ;
HENNIGHAUSEN, L .
JOURNAL OF VIROLOGY, 1988, 62 (03) :1076-1079
[10]   PREVENTION OF TRANSFUSION-ACQUIRED CYTOMEGALO-VIRUS INFECTION IN INFANTS BY BLOOD FILTRATION TO REMOVE LEUKOCYTES [J].
GILBERT, GL ;
HUDSON, IL ;
HAYES, K ;
JAMES, J .
LANCET, 1989, 1 (8649) :1228-1231