PMID- 20551916
OWN - NLM
STAT- MEDLINE
DCOM- 20101123
LR  - 20211020
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 18
IP  - 8
DP  - 2010 Aug
TI  - Recognition of virus infection and innate host responses to viral gene therapy 
      vectors.
PG  - 1422-9
LID - 10.1038/mt.2010.124 [doi]
AB  - The innate immune and inflammatory response represents one of the key stumbling 
      blocks limiting the efficacy of viral-based therapies. Numerous human diseases 
      could be corrected or ameliorated if viruses were harnessed to safely and 
      effectively deliver therapeutic genes to diseased cells and tissues in vivo. 
      Recent studies have shown that host cells recognize viruses using an elaborate 
      network of sensor proteins localized at the plasma membrane, in endosomes, or in 
      the cytosol. Three classes of sensors have been implicated in sensing viruses in 
      mammalian cells-Toll-like receptors (TLRs), retinoid acid-inducible gene 
      (RIG)-I-like receptors (RLRs), and nucleotide oligomerization domain (NOD)-like 
      receptors (NLRs). The interaction of virus-associated nucleic acids with these 
      sensor molecules triggers a signaling cascade that activates the principal host 
      defense program aimed to limit or eliminate virus infection and restore tissue 
      homeostasis. In addition, recent data strongly suggest that host cells can mount 
      innate immune responses to viruses without prior recognition of their nucleic 
      acids. To deliver therapeutic genes into the nuclei of diseased cells, viral gene 
      therapy vectors must be efficient at penetrating either the plasma or endosomal 
      membrane. The therapeutic use of high numbers of virus particles disturbs 
      cellular homeostasis, triggering cell damage and stress pathways, or "sensing of 
      modified self". Accumulating data indicate that the sensing of modified self 
      might represent a powerful framework explaining the innate immune response 
      activation by viral gene therapy vectors.
FAU - Shayakhmetov, Dmitry M
AU  - Shayakhmetov DM
AD  - Division of Medical Genetics, Department of Medicine, University of Washington, 
      Seattle, WA, USA. dshax@uw.edu
FAU - Di Paolo, Nelson C
AU  - Di Paolo NC
FAU - Mossman, Karen L
AU  - Mossman KL
LA  - eng
GR  - CAPMC/CIHR/Canada
GR  - R01 AI065429/AI/NIAID NIH HHS/United States
GR  - CA141439/CA/NCI NIH HHS/United States
GR  - R01 CA141439/CA/NCI NIH HHS/United States
GR  - AI065429/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20100615
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - *Genetic Therapy
MH  - Genetic Vectors/*genetics
MH  - Humans
MH  - Models, Biological
MH  - Toll-Like Receptors/genetics/metabolism
MH  - Viruses/*genetics
PMC - PMC2927067
EDAT- 2010/06/17 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/08/01
CRDT- 2010/06/17 06:00
PHST- 2010/06/17 06:00 [entrez]
PHST- 2010/06/17 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - S1525-0016(16)31091-7 [pii]
AID - 10.1038/mt.2010.124 [doi]
PST - ppublish
SO  - Mol Ther. 2010 Aug;18(8):1422-9. doi: 10.1038/mt.2010.124. Epub 2010 Jun 15.