1. Human T lymphotropic virus type 1 increases T lymphocyte migration by recruiting the cytoskeleton organizer CRMP2.
- Author
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Varrin-Doyer M, Nicolle A, Marignier R, Cavagna S, Benetollo C, Wattel E, and Giraudon P
- Subjects
- Antigens, CD, Antigens, Differentiation, T-Lymphocyte, Cytoskeleton virology, Humans, Inflammation virology, Intercellular Signaling Peptides and Proteins physiology, Lectins, C-Type, Nerve Tissue Proteins physiology, Phosphatidylinositol 3-Kinases metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt metabolism, T-Lymphocytes physiology, Viral Proteins, Cell Movement, Human T-lymphotropic virus 1 physiology, Intercellular Signaling Peptides and Proteins metabolism, Nerve Tissue Proteins metabolism, T-Lymphocytes virology
- Abstract
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.
- Published
- 2012
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