Interaction of CD82 tetraspanin proteins with HTLV-1 envelope glycoproteins inhibits cell-to-cell fusion and virus transmission.
The entry of retroviruses into their target cell involves interactions between the virus envelope glycoproteins and their cellular receptors, as well as accessory ligand-receptor interactions involving adhesion molecules that can also participate in fusion. We have studied the contribution of CD82 proteins to the transmission of the human T-cell leukemia virus type 1 (HTLV-1), which is greatly dependent on cell-to-cell contacts. CD82 proteins belong to a class of cell surface molecules, the tetraspanins, that can act as molecular facilitators in cellular adhesion processes. The coexpression of CD82 proteins with HTLV-1 envelope glycoproteins resulted in marked inhibition of syncytium formation, whereas CD82 proteins had no effect on syncytium formation induced by human immunodeficiency virus type 1 (HIV-1) envelope proteins. The presence of CD82 proteins also inhibited cell-to-cell transmission of HTLV-1. Coimmunoprecipitation and cocapping experiments showed that CD82 associates with HTLV-1 envelope glycoproteins, both within the cell and at the cell surface. Finally, whereas the intracellular maturation of HTLV-1 glycoproteins was not modified by the presence of CD82 proteins, HTLV-1 protein coproduction delayed the intracellular maturation of CD82 proteins. There thus seems to be a reciprocal interaction between virus and cell proteins, and the cellular proteins involved in adhesion modulate retrovirus transmission both positively, as shown in other systems, and negatively, as shown here.
Pique
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C
Hôpital Saint Louis, Centre National de la Recherche Scientifique (CNRS) Unité Propre de Recherche (UPR) 9051. pique@chu-stlouis.fr
Lagaudrière-Gesbert
C
C
Delamarre
L
L
Rosenberg
A R
AR
Conjeaud
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H
Dokhélar
M C
MC
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D019556:COS Cells; D002459:Cell Fusion; D002460:Cell Line; D015686:Gene Products, env / Q000378:metabolism*; D015726:Giant Cells / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D013601:T-Lymphocytes / Q000821:virology; D014162:Transfection
D015703:Antigens, CD; D015686:Gene Products, env; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic