PMID- 22390651
OWN - NLM
STAT- MEDLINE
DCOM- 20121012
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Linking)
VI  - 12
IP  - 6
DP  - 2012 Jun
TI  - CMV late phase-induced mTOR activation is essential for efficient virus 
      replication in polarized human macrophages.
PG  - 1458-68
LID - 10.1111/j.1600-6143.2012.04002.x [doi]
AB  - Human cytomegalovirus (CMV) remains one of the most important pathogens following 
      solid-organ transplantation. Mounting evidence indicates that mammalian target of 
      rapamycin (mTOR) inhibitors may decrease the incidence of CMV infection in 
      solid-organ recipients. Here we aimed at elucidating the molecular mechanisms of 
      this effect by employing a human CMV (HCMV) infection model in human macrophages, 
      since myeloid cells are the principal in vivo targets of HCMV. We demonstrate a 
      highly divergent host cell permissiveness for HCMV with optimal infection 
      susceptibility in M2 but not M1 polarized macrophages. Employing an ultrahigh 
      purified HCMV stock we observed rapamycin-independent viral entry and induction 
      of IFN-beta transcripts, but no proinflammatory cytokines or mitogen-activated 
      protein kinases and mTOR activation early after infection. However, in the late 
      infection phase, sustained mTOR activation was observed in HCMV-infected cells 
      and was required for efficient viral protein synthesis including the viral late 
      phase proteins pUL-44 and pp65. Accordingly, rapamycin strongly suppressed CMV 
      replication 3 and 5 days postinfection in macrophages. In conclusion, these data 
      indicate that mTOR is essential for virus replication during late phases of the 
      viral cycle in myeloid cells and might explain the potent anti-CMV effects of 
      mTOR inhibitors after organ transplantation.
CI  - (c) Copyright 2012 The American Society of Transplantation and the American Society 
      of Transplant Surgeons.
FAU - Poglitsch, M
AU  - Poglitsch M
AD  - Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical 
      University of Vienna, Vienna, Austria.
FAU - Weichhart, T
AU  - Weichhart T
FAU - Hecking, M
AU  - Hecking M
FAU - Werzowa, J
AU  - Werzowa J
FAU - Katholnig, K
AU  - Katholnig K
FAU - Antlanger, M
AU  - Antlanger M
FAU - Krmpotic, A
AU  - Krmpotic A
FAU - Jonjic, S
AU  - Jonjic S
FAU - Horl, W H
AU  - Horl WH
FAU - Zlabinger, G J
AU  - Zlabinger GJ
FAU - Puchhammer, E
AU  - Puchhammer E
FAU - Saemann, M D
AU  - Saemann MD
LA  - eng
GR  - R01 AI083201/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20120305
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Cytomegalovirus/*physiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Immunohistochemistry
MH  - Macrophages/*virology
MH  - Membrane Fusion
MH  - Polymerase Chain Reaction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - *Virus Replication
EDAT- 2012/03/07 06:00
MHDA- 2012/10/13 06:00
CRDT- 2012/03/07 06:00
PHST- 2012/03/07 06:00 [entrez]
PHST- 2012/03/07 06:00 [pubmed]
PHST- 2012/10/13 06:00 [medline]
AID - S1600-6135(22)27475-9 [pii]
AID - 10.1111/j.1600-6143.2012.04002.x [doi]
PST - ppublish
SO  - Am J Transplant. 2012 Jun;12(6):1458-68. doi: 10.1111/j.1600-6143.2012.04002.x. 
      Epub 2012 Mar 5.