AUTHOR=Izumida Mai , Kamiyama Haruka , Suematsu Takashi , Honda Eri , Koizumi Yosuke , Yasui Kiyoshi , Hayashi Hideki , Ariyoshi Koya , Kubo Yoshinao TITLE=Fragments of Target Cells are Internalized into Retroviral Envelope Protein-Expressing Cells during Cell-Cell Fusion by Endocytosis JOURNAL=Frontiers in Microbiology VOLUME=6 YEAR=2016 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.01552 DOI=10.3389/fmicb.2015.01552 ISSN=1664-302X ABSTRACT=

Retroviruses enter into host cells by fusion between viral and host cell membranes. Retroviral envelope glycoprotein (Env) induces the membrane fusion, and also mediates cell-cell fusion. There are two types of cell-cell fusions induced by the Env protein. Fusion-from-within is induced by fusion between viral fusogenic Env protein-expressing cells and susceptible cells, and virions induce fusion-from-without by fusion between adjacent cells. Although entry of ecotropic murine leukemia virus (E-MLV) requires host cell endocytosis, the involvement of endocytosis in cell fusion is unclear. By fluorescent microscopic analysis of the fusion-from-within, we found that fragments of target cells are internalized into Env-expressing cells. Treatment of the Env-expressing cells with an endocytosis inhibitor more significantly inhibited the cell fusion than that of the target cells, indicating that endocytosis in Env-expressing cells is required for the cell fusion. The endocytosis inhibitor also attenuated the fusion-from-without. Electron microscopic analysis suggested that the membrane fusion resulting in fusion-from-within initiates in endocytic membrane dents. This study shows that two types of the viral cell fusion both require endocytosis, and provides the cascade of fusion-from-within.