PMID- 12153529
OWN - NLM
STAT- MEDLINE
DCOM- 20021009
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 16
IP  - 1
DP  - 2002 Jul
TI  - Intranasal herpes simplex virus type 2 inoculation causes a profound thymidine 
      kinase dependent cerebral inflammatory response in the mouse hindbrain.
PG  - 29-43
AB  - The herpes simplex virus (HSV) has the ability to replicate in the central 
      nervous system (CNS), which may cause fatal encephalitis. The present study 
      investigated the activity of the nuclear factor kappa B (NF-kappa B) and the 
      pattern of cytokine/chemokine gene expression across the brain of HSV-infected 
      mice and the role of the viral thymidine kinase (TK) in mediating these effects. 
      Mice were killed 1-8 days after intranasal inoculation with either HSV-2 
      TK-competent or TK-deficient clinical isolates. Animals infected with the 
      TK-competent virus exhibited first signs of infection at day 5 postinoculation, 
      whereas severe signs of sickness were observed between day 6 and 8. A robust 
      hybridization signal was found in the brain of these animals for the gene 
      encoding the inhibitory factor kappa B alpha (I kappa B alpha, index of NF-kappa 
      B activity), toll-like receptor 2 (TLR2), tumour necrosis factor alpha 
      (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) in numerous regions of 
      the pons and medulla. The levels of expression of these genes increased 4 days 
      after the inoculation and peaked at day 6 within the endothelium of the brain 
      capillaries and cells of myeloid origin. A robust signal for the TK gene and its 
      encoding protein was detected selectively within the regions that exhibited 
      expression of the immune molecules. In contrast, animals that received the 
      TK-deficient virus did not show any signs of sickness or cerebral inflammation or 
      HSV replication within the cerebral tissue. The present data provide clear 
      evidence that HSV-2 has the ability to trigger a profound inflammatory response 
      in a pattern that follows the viral TK-dependent HSV replication in neurons. Such 
      neurovirulence occurring in the hindbrain is proposed here to be directly 
      responsible for neurodegeneration and to lead to the cerebral innate immune 
      response, which in turn could play a key role in fatal HSV-2-induced 
      encephalitis.
FAU - Boivin, Guy
AU  - Boivin G
AD  - Laboratory of Infectious Diseases, CHUL Research Centre and Laval University, 
      2705, boul. Laurier, Quebec, G1V 4G Canada.
FAU - Coulombe, Zoe
AU  - Coulombe Z
FAU - Rivest, Serge
AU  - Rivest S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.1.21 (Thymidine Kinase)
SB  - IM
MH  - Administration, Intranasal
MH  - Animals
MH  - Chemokine CCL2/genetics/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - *Drosophila Proteins
MH  - Female
MH  - Herpesvirus 2, Human/*pathogenicity
MH  - *I-kappa B Proteins
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Inflammation/enzymology/virology
MH  - Interferon-gamma/metabolism
MH  - Medulla Oblongata/enzymology/virology
MH  - Membrane Glycoproteins/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/metabolism
MH  - Pons/enzymology/virology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Rhombencephalon/*enzymology/*virology
MH  - Thymidine Kinase/genetics/*metabolism
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptors
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
EDAT- 2002/08/03 10:00
MHDA- 2002/10/10 04:00
CRDT- 2002/08/03 10:00
PHST- 2002/08/03 10:00 [pubmed]
PHST- 2002/10/10 04:00 [medline]
PHST- 2002/08/03 10:00 [entrez]
AID - 2057 [pii]
AID - 10.1046/j.1460-9568.2002.02057.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2002 Jul;16(1):29-43. doi: 10.1046/j.1460-9568.2002.02057.x.