PMID- 15163738
OWN - NLM
STAT- MEDLINE
DCOM- 20040629
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 78
IP  - 12
DP  - 2004 Jun
TI  - MCP-1 and CCR2 contribute to non-lymphocyte-mediated brain disease induced by 
      Fr98 polytropic retrovirus infection in mice: role for astrocytes in retroviral 
      neuropathogenesis.
PG  - 6449-58
AB  - Virus infection of the central nervous system (CNS) often results in chemokine 
      upregulation. Although often associated with lymphocyte recruitment, increased 
      chemokine expression is also associated with non-lymphocyte-mediated CNS disease. 
      In these instances, the effect of chemokine upregulation on neurological disease 
      is unclear. In vitro, several chemokines including monocyte chemotactic protein 1 
      (MCP-1) protect neurons from apoptosis. Therefore, in vivo, chemokine 
      upregulation may be a protective host response to CNS damage. Alternatively, 
      chemokines may contribute to pathogenesis by stimulating intrinsic brain cells or 
      recruiting macrophages to the brain. To investigate these possibilities, we 
      studied a neurovirulent retrovirus, Fr98, that induces severe 
      non-lymphocyte-mediated neurological disease and causes the upregulation of 
      several chemokines that bind to chemokine receptors CCR2 and CCR5. Knockout mice 
      deficient in CCR2 had reduced susceptibility to Fr98 pathogenesis, with 
      significantly fewer mice developing clinical disease than did wild-type controls. 
      In contrast, no reduction in Fr98-induced disease was observed in CCR5 knockout 
      mice. Thus, signaling through CCR2, but not CCR5, plays an important role in 
      Fr98-mediated pathogenesis. Three ligands for CCR2 (MCP-1, MCP-3, and MCP-5) were 
      upregulated during Fr98 infection of the brain. Antibody-blocking experiments 
      demonstrated that MCP-1 was important for retrovirus-induced neurological 
      disease. In situ hybridization analysis revealed that MCP-1 was expressed by 
      glial fibrillary acidic protein-positive astrocytes. Thus, astrocytes, previously 
      not thought to play an effector role in the disease process were found to 
      contribute to pathogenesis through the production of MCP-1. This study also 
      demonstrates that chemokines can mediate pathogenesis in the CNS in the absence 
      of lymphocytic infiltrate and gives credence to the hypothesis that chemokine 
      upregulation is a mechanism by which retroviruses such as human immunodeficiency 
      virus induce neurological damage.
FAU - Peterson, Karin E
AU  - Peterson KE
AD  - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National 
      Institute of Allergy and Infectious Disease/NIH, 903 S. 4th Street, Hamilton, MT 
      59840, USA.
FAU - Errett, John S
AU  - Errett JS
FAU - Wei, Tao
AU  - Wei T
FAU - Dimcheff, Derek E
AU  - Dimcheff DE
FAU - Ransohoff, Richard
AU  - Ransohoff R
FAU - Kuziel, William A
AU  - Kuziel WA
FAU - Evans, Leonard
AU  - Evans L
FAU - Chesebro, Bruce
AU  - Chesebro B
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CCL7 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Ccl12 protein, mouse)
RN  - 0 (Ccl7 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL7)
RN  - 0 (Cytokines)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Monocyte Chemoattractant Proteins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Brain/metabolism/virology
MH  - Brain Diseases/*physiopathology/virology
MH  - Chemokine CCL2/*metabolism
MH  - Chemokine CCL7
MH  - *Cytokines
MH  - Gene Deletion
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Lymphocytes/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Monocyte Chemoattractant Proteins/metabolism
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics/*metabolism
MH  - Retroviridae/*pathogenicity
MH  - Retroviridae Infections/*physiopathology/virology
MH  - Up-Regulation
MH  - Virulence
MH  - Virus Replication
PMC - PMC416512
EDAT- 2004/05/28 05:00
MHDA- 2004/06/30 05:00
PMCR- 2004/06/01
CRDT- 2004/05/28 05:00
PHST- 2004/05/28 05:00 [pubmed]
PHST- 2004/06/30 05:00 [medline]
PHST- 2004/05/28 05:00 [entrez]
PHST- 2004/06/01 00:00 [pmc-release]
AID - 78/12/6449 [pii]
AID - 2204-03 [pii]
AID - 10.1128/JVI.78.12.6449-6458.2004 [doi]
PST - ppublish
SO  - J Virol. 2004 Jun;78(12):6449-58. doi: 10.1128/JVI.78.12.6449-6458.2004.