PMID- 25694602
OWN - NLM
STAT- MEDLINE
DCOM- 20150610
LR  - 20181113
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 89
IP  - 9
DP  - 2015 May
TI  - The retinoblastoma tumor suppressor promotes efficient human cytomegalovirus 
      lytic replication.
PG  - 5012-21
LID - 10.1128/JVI.00175-15 [doi]
AB  - The retinoblastoma (Rb) tumor suppressor controls cell cycle, DNA damage, 
      apoptotic, and metabolic pathways. DNA tumor virus oncoproteins reduce Rb 
      function by either inducing Rb degradation or physically disrupting complexes 
      between Rb and its myriad binding proteins. Human cytomegalovirus (HCMV), a 
      betaherpesvirus being investigated for potential roles in human cancers, encodes 
      multiple lytic-phase proteins that inactivate Rb in distinct ways, leading to the 
      hypothesis that reduced Rb levels and/or activity would benefit HCMV lytic 
      infection. Paradoxically, we found that Rb knockdown prior to infection, whether 
      transient or constitutive, impaired HCMV lytic infection at multiple stages, 
      notably viral DNA replication, late protein expression, and infectious virion 
      production. The existence of differentially modified forms of Rb, the temporally 
      and functionally distinct means by which HCMV proteins interact with Rb, and the 
      necessity of Rb for efficient HCMV lytic replication combine to highlight the 
      complex relationship between the virus and this critical tumor suppressor. 
      IMPORTANCE: Initial work examining viral protein modulation of cell cycle 
      progression and oncogenic transformation revealed that these proteins inactivated 
      the function of cellular tumor suppressor proteins. However, subsequent work, 
      including experiments described here using human cytomegalovirus, demonstrate a 
      more nuanced interaction that includes the necessity of cellular tumor 
      suppressors for efficient viral replication. Understanding the positive impacts 
      that cellular tumor suppressors have on viral infections may reveal new 
      activities of these well-studied yet incompletely understood proteins. The basis 
      for oncolytic viral therapy is the selective replication of viruses in 
      transformed cells in which tumor suppressor function may be compromised. 
      Understanding how tumor suppressors support viral infections may allow for the 
      generation of modified oncolytic viruses with greater selective tumor cell 
      replication and killing.
CI  - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved.
FAU - VanDeusen, Halena R
AU  - VanDeusen HR
AD  - Institute for Molecular Virology and McArdle Laboratory for Cancer Research, 
      University of Wisconsin-Madison, Madison, Wisconsin, USA.
FAU - Kalejta, Robert F
AU  - Kalejta RF
AD  - Institute for Molecular Virology and McArdle Laboratory for Cancer Research, 
      University of Wisconsin-Madison, Madison, Wisconsin, USA rfkalejta@wisc.edu.
LA  - eng
GR  - R01 AI080675/AI/NIAID NIH HHS/United States
GR  - T32 CA009135/CA/NCI NIH HHS/United States
GR  - AI080675/AI/NIAID NIH HHS/United States
GR  - T32CA009135/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150218
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Cells, Cultured
MH  - Cytomegalovirus/*physiology
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Retinoblastoma Protein/*metabolism
MH  - *Virus Replication
PMC - PMC4403481
EDAT- 2015/02/20 06:00
MHDA- 2015/06/11 06:00
PMCR- 2015/11/01
CRDT- 2015/02/20 06:00
PHST- 2015/01/20 00:00 [received]
PHST- 2015/02/13 00:00 [accepted]
PHST- 2015/02/20 06:00 [entrez]
PHST- 2015/02/20 06:00 [pubmed]
PHST- 2015/06/11 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - JVI.00175-15 [pii]
AID - 00175-15 [pii]
AID - 10.1128/JVI.00175-15 [doi]
PST - ppublish
SO  - J Virol. 2015 May;89(9):5012-21. doi: 10.1128/JVI.00175-15. Epub 2015 Feb 18.