Long-term effects of HTLV-1 on brain astrocytes: sustained expression of Tax-1 associated with synthesis of inflammatory mediators.
HTLV-1 is the causative agent of a chronic neurological disease, TSP/HAM. The persistently activated CTL response to the viral protein Tax-1 suggests the existence of persistent viral replication with continuous expression of Tax-1. Although CD4+ T-cell is the main target for HTLV-1, previous observations have indicated that the astrocyte, the major neural cell in close contact with blood vessel and thus with HTLV-1-infected T-cells infiltrating the CNS, may also be infected. We tested in vitro the hypothesis of persistent/restricted infection in human and rat astrocytes after transient contact with an infectious T-cell line (C91PL). Long-term analysis showed prolonged expression of Tax-1 in astrocytes, associated with secretion of inflammatory mediators (TNFalpha, IL1alpha, MMP-2, and MMP-9). These data suggest a possible contribution of Tax-1-expressing astrocytes to TSP/HAM pathogenesis.
Szymocha
R
R
INSERM U433, Faculté de Médecine R. Laënec, 69372 Lyon Cedex 08, France.
Brisson
C
C
Bernard
A
A
Akaoka
H
H
Belin
M F
MF
Giraudon
P
P
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D015139:Blotting, Southern; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis*; D002478:Cells, Cultured; D018920:Coculture Techniques; D058969:Contactin 2; D015368:Human T-lymphotropic virus 1; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000032:analysis*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015682:Retroviridae Proteins, Oncogenic / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C548676:Cntn2 protein, rat; D058969:Contactin 2; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; D014409:Tumor Necrosis Factor-alpha; C060954:p24 protein, Human T-lymphotropic virus 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9