Human T lymphotropic virus type 1 increases T lymphocyte migration by recruiting the cytoskeleton organizer CRMP2

Recruitment of virus-infected T lymphocytes into the CNS is an essential step in the development of virus-associated neuroinflammatory diseases, notably myelopathy induced by retrovirus human T leukemia virus-1 (HTLV-1). We have recently shown the key role of collapsin response mediator protein 2 (C...

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Published in:The Journal of immunology (1950) 2012-02, Vol.188 (3), p.1222-1233
Main Authors: Varrin-Doyer, Michel, Nicolle, Adeline, Marignier, Romain, Cavagna, Sylvie, Benetollo, Claire, Wattel, Eric, Giraudon, Pascale
Format: Article
Language:English
Subjects:
Antigens, CD
Antigens, Differentiation, T-Lymphocyte
Cell Movement
Cytoskeleton - virology
Human T-lymphotropic virus 1
Human T-lymphotropic virus 1 - physiology
Humans
Inflammation - virology
Intercellular Signaling Peptides and Proteins - metabolism
Intercellular Signaling Peptides and Proteins - physiology
Lectins, C-Type
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - physiology
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
T-Lymphocytes - physiology
T-Lymphocytes - virology
Viral Proteins
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Summary:Recruitment of virus-infected T lymphocytes into the CNS is an essential step in the development of virus-associated neuroinflammatory diseases, notably myelopathy induced by retrovirus human T leukemia virus-1 (HTLV-1). We have recently shown the key role of collapsin response mediator protein 2 (CRMP2), a phosphoprotein involved in cytoskeleton rearrangement, in the control of human lymphocyte migration and in brain targeting in animal models of virus-induced neuroinflammation. Using lymphocytes cloned from infected patients and chronically infected T cells, we found that HTLV-1 affects CRMP2 activity, resulting in an increased migratory potential. Elevated CRMP2 expression accompanies a higher phosphorylation level of CRMP2 and its more pronounced adhesion to tubulin and actin. CRMP2 forms, a full length and a shorter, cleaved one, are also affected. Tax transfection and extinction strategies show the involvement of this viral protein in enhanced full-length and active CRMP2, resulting in prominent migratory rate. A role for other viral proteins in CRMP2 phosphorylation is suspected. Full-length CRMP2 confers a migratory advantage possibly by preempting the negative effect of short CRMP2 we observe on T lymphocyte migration. In addition, HTLV-1-induced migration seems, in part, supported by the ability of infected cell to increase the proteosomal degradation of short CRMP2. Finally, gene expression in CD69(+) cells selected from patients suggests that HTLV-1 has the capacity to influence the CRMP2/PI3K/Akt axis thus to positively control cytoskeleton organization and lymphocyte migration. Our data provide an additional clue to understanding the infiltration of HTLV-1-infected lymphocytes into various tissues and suggest that the regulation of CRMP2 activity by virus infection is a novel aspect of neuroinflammation.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1101562