Gem-Induced Cytoskeleton Remodeling Increases Cellular Migration of HTLV-1-Infected Cells,Formation of Infected-to-Target T-Cell Conjugates and Viral Transmission

Efficient htlv-1 viral transmission occurs through cell-to-cell contacts. the tax viral transcriptional activator protein facilitates this process. using a comparative transcriptomic analysis,we recently identified a series of genes up-regulated in htlv-1 tax expressing t-lymphocytes. we focused our attention towards genes that are important for cytoskeleton dynamic and thus may possibly modulate cell-to-cell contacts. we first demonstrate that gem,a member of the small gtp-binding proteins within the ras superfamily,is expressed both at the rna and protein levels in tax-expressing cells and in htlv-1-infected cell lines. using a series of chip assays,we show that tax recruits creb and creb binding protein (cbp) onto a c-amp responsive element (cre) present in the gem promoter. this cre sequence is required to drive tax-activated gem transcription. since gem is involved in cytoskeleton remodeling,we investigated its role in infected cells motility. we show that gem co-localizes with f-actin and is involved both in t-cell spontaneous cell migration as well as chemotaxis in the presence of sdf-1/cxcl12. importantly,gem knock-down in htlv-1-infected cells decreases cell migration and conjugate formation. finally,we demonstrate that gem plays an important role in cell-to-cell viral transmission.