PMID- 25312585
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20220129
IS  - 1465-2099 (Electronic)
IS  - 0022-1317 (Print)
IS  - 0022-1317 (Linking)
VI  - 96
IP  - Pt 1
DP  - 2015 Jan
TI  - Glucocorticosteroids trigger reactivation of human cytomegalovirus from latently 
      infected myeloid cells and increase the risk for HCMV infection in D+R+ liver 
      transplant patients.
PG  - 131-143
LID - 10.1099/vir.0.069872-0 [doi]
AB  - Graft rejection in transplant patients is managed clinically by suppressing 
      T-cell function with immunosuppressive drugs such as prednisolone and 
      methylprednisolone. In such immunocompromised hosts, human cytomegalovirus (HCMV) 
      is an important opportunistic pathogen and can cause severe morbidity and 
      mortality. Currently, the effect of glucocorticosteroids (GCSs) on the HCMV life 
      cycle remains unclear. Previous reports showed enhanced lytic replication of HCMV 
      in vitro in the presence of GCSs. In the present study, we explored the 
      implications of steroid exposure on latency and reactivation. We observed a 
      direct effect of several GCSs used in the clinic on the activation of a quiescent 
      viral major immediate-early promoter in stably transfected THP-1 monocytic cells. 
      This activation was prevented by the glucocorticoid receptor (GR) antagonist 
      Ru486 and by shRNA-mediated knockdown of the GR. Consistent with this 
      observation, prednisolone treatment of latently infected primary monocytes 
      resulted in HCMV reactivation. Analysis of the phenotype of these cells showed 
      that treatment with GCSs was correlated with differentiation to an 
      anti-inflammatory macrophage-like cell type. On the basis that these observations 
      may be pertinent to HCMV reactivation in post-transplant settings, we 
      retrospectively evaluated the incidence, viral kinetics and viral load of HCMV in 
      liver transplant patients in the presence or absence of GCS treatment. We 
      observed that combination therapy of baseline prednisolone and augmented 
      methylprednisolone, upon organ rejection, significantly increased the incidence 
      of HCMV infection in the intermediate risk group where donor and recipient are 
      both HCMV seropositive (D+R+) to levels comparable with the high risk D+R- group.
CI  - (c) 2015 The Authors.
FAU - Van Damme, Ellen
AU  - Van Damme E
AD  - Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium.
FAU - Sauviller, Sarah
AU  - Sauviller S
AD  - Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium.
FAU - Lau, Betty
AU  - Lau B
AD  - Department of Medicine, University of Cambridge, Level 5, Addenbrooke's Hospital, 
      Hills Road, Cambridge CB2 0QQ, UK.
FAU - Kesteleyn, Bart
AU  - Kesteleyn B
AD  - Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium.
FAU - Griffiths, Paul
AU  - Griffiths P
AD  - Division of Infection and Immunity (Royal Free Campus), University College 
      London, Rowland Hill Street, Hampstead, London NW3 2QG, UK.
FAU - Burroughs, Andrew
AU  - Burroughs A
AD  - Sheila Sherlock Liver Centre, Royal Free NHS Trust, Hampstead, London NW3 2QG, 
      UK.
FAU - Emery, Vincent
AU  - Emery V
AD  - Department of Microbial and Cellular Sciences, University of Surrey, Guildford, 
      Surrey GU2 7XH, UK.
AD  - Division of Infection and Immunity (Royal Free Campus), University College 
      London, Rowland Hill Street, Hampstead, London NW3 2QG, UK.
FAU - Sinclair, John
AU  - Sinclair J
AD  - Department of Medicine, University of Cambridge, Level 5, Addenbrooke's Hospital, 
      Hills Road, Cambridge CB2 0QQ, UK.
FAU - Van Loock, Marnix
AU  - Van Loock M
AD  - Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium.
LA  - eng
GR  - G0701279/MRC_/Medical Research Council/United Kingdom
GR  - MR/K021087/1/MRC_/Medical Research Council/United Kingdom
GR  - G:0701279/MRC_/Medical Research Council/United Kingdom
GR  - 078332/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141013
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cell Differentiation/physiology
MH  - Cell Line
MH  - Communicable Diseases/metabolism/virology
MH  - Cytomegalovirus/*physiology
MH  - Cytomegalovirus Infections/*metabolism/virology
MH  - Female
MH  - Glucocorticoids/*metabolism
MH  - Humans
MH  - Immunocompromised Host/physiology
MH  - Liver/metabolism/*virology
MH  - Liver Transplantation/methods
MH  - Male
MH  - Middle Aged
MH  - Monocytes/metabolism/virology
MH  - Myeloid Cells/metabolism/*virology
MH  - Receptors, Glucocorticoid/metabolism
MH  - Viral Load/physiology
MH  - Virus Activation/*physiology
MH  - Virus Latency/*physiology
MH  - Young Adult
PMC - PMC4268819
EDAT- 2014/10/15 06:00
MHDA- 2015/03/31 06:00
PMCR- 2015/01/01
CRDT- 2014/10/15 06:00
PHST- 2014/10/15 06:00 [entrez]
PHST- 2014/10/15 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 069872 [pii]
AID - 10.1099/vir.0.069872-0 [doi]
PST - ppublish
SO  - J Gen Virol. 2015 Jan;96(Pt 1):131-143. doi: 10.1099/vir.0.069872-0. Epub 2014 
      Oct 13.