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A CD63 mutant inhibits T-cell tropic human immunodeficiency virus type 1 entry by disrupting CXCR4 trafficking to the plasma membrane |
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| Authors: | Yoshida Takeshi Kawano Yuji Sato Kei Ando Yoshinori Aoki Jun Miura Yoshiharu Komano Jun Tanaka Yuetsu Koyanagi Yoshio |
| Institution: | Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Neurology, Neurological Institute, Graduate School of Medical Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan; AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan |
| Abstract: | We have discovered that an N-terminal deletion mutant of a membrane protein, CD63, (CD63ΔN) blocks entry of CXCR4-using, T-cell tropic human immunodeficiency virus type 1 (X4 HIV-1) by suppressing CXCR4 surface expression. This suppression was observed for CXCR4 but not for CD4, CCR5, CD25, CD71 or other tetraspanin proteins. The suppression of CXCR4 expression on the plasma membrane appeared to be caused by mislocalization of CXCR4 and exclusive transportation of CXCR4 toward intracellular organelles, mainly late endosomes/lysosomes. Our data suggest that CXCR4 trafficking can be modified in terms of its recruitment to the plasma membrane without enhancing the degradation or arresting vesicular transport of CXCR4. |
| Keywords: | cell surface expression CD63 CXCR4 HIV-1 ligand-independent trafficking |
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