Cell-to-cell Transmission of Htlv-i

摘要

Cell-to-cell transmission of human T-cell leukemia virus type I (HTLV-I) is initiated with the interaction between viral envelope proteins and the host cell receptor, thus leading to HTLV-I cell entry via membrane fusion. Viral envelope attachment to the cellular receptor is mediated through receptor binding sites on amino acids 111 to 136 (gp46-lll) and 197 to 216 (gp46-197) on the gp46 surface envelope glycoprotein, and 400 to 429 (gp21-400) on the gp21 transmembrane glycoprotein, respectively. Cellular receptors for cell-to-cell transmission of HTLV-I consist of a 71 kDa heat shock cognate protein (HSC70), (3-actin and palmitoyl(16:0)-ole-oyl(18:l)-phosphatidylglycerol (POPG) and these three receptor molecules form a receptor complex in target cell membrane, as a core molecule of HSC70. Infectivity-neutralizing antibodies bind to the sites surrounding the receptor-binding pockets, gp46-lll and gp46-197 on gp46, and structure of the complexes between neutralizing antibody and gp46 indicate a possible neutralizing mechanism. Thus, gp46 is the receptor binding and membrane fusion glycoprotein of HTLV-I and the target for infectivity-neutralizing antibodies. These findings provide a frame for developing therapeutic and preventative strategies to combat HTLV-I pathologenesis, as well as data on the basic biology of HTLV-I, including the selective tropism of virus and membrane fusion mechanisms governing virus entry.